Maternal Separation

Long (LMS) versus brief (BMS) daily separations of rat pups from their mothers have contrasting effects on their adult stress responses and maternal behavior by respectively decreasing and increasing licking received from their mothers. We hypothesized that LMS decreases pup licking in mothers by inducing learned helplessness, creating a depression-like state. We subjected postpartum rats to LMS (3 h), BMS (15 min) or no separation (NMS) on postpartum days 2-14. After weaning, mothers were given a forced swim test (FST). LMS mothers exhibited more immobility and fewer escape attempts than BMS or NMS mothers. These results suggest that LMS induces a depressionlike state, which may account for the reductions in maternal behavior seen in LMS mothers. Immobility in the FST is recognized as an animal model of depression. Therefore, LMS may be a model of maternal depression.

Adverse conditions during early life are a risk factor for stress-related diseases. How this early adversity induce long-term effects is not well understood, however there are several evidence that the stress hormones play a determining role. Here we will focus on evidence obtained from the long-term consequences of prolonged maternal separation procedures. The purpose of this article is to review the literature about the influence of early experiences on the hypothalamic-pituitaryadrenal (HPA) axis function and endocrine stress responses in rodents. Early experiences have long-term influences on the behavioral and endocrine responses to stress and the alterations depend mostly on environment conditions and the interaction between mother and offspring. In the rodent, brief periods of separation result in an attenuated adrenal response to stress (reduced secretion of corticosterone). In contrast, longer periods of separation result in an exaggerated response. Besides, it is known tha...

Family Nurture Intervention (FNI) is designed to facilitate affective connections between prematurely born infants and their mothers. At term age, prematurely born infants with FNI had robust increases in frontal brain activity. Promoting early nurturing interactions may improve neurobehavioral outcomes of preterm infants. Objective: To assess the impact of Family Nurture Intervention (FNI) on electroencephalogram (EEG) activity in preterm infants (26-34 weeks gestation). Methods: Two groups were tested in a single, level IV neonatal intensive care unit (NICU; standard care or standard care plus FNI) using a randomized controlled trial design. The intervention consists of sessions designed to achieve mutual calm and promote communication of affect between infants and their mothers throughout the NICU stay. EEG recordings were obtained from 134 infants during sleep at $35 and $40 weeks postmenstrual age (PMA). Regional brain activity (power) was computed for 10 frequency bands between 1 and 48 Hz in each of 125 electrodes. Results: Near to term age, compared to standard care infants, FNI infants showed robust increases in EEG power in the frontal polar region at frequencies 10 to 48 Hz (20% to 36% with p-values <0.0004). Effects were significant in both quiet and active sleep, regardless of gender, singleton-twin status, gestational age (26-30 or 30-35 weeks) or birth weight (<1500 or >1500 g). Conclusion: FNI leads to increased frontal brain activity during sleep, which other investigators find predictive of better neurobehavioral outcomes. Significance: FNI may be a practicable means of improving outcomes in preterm infants.

Objective: This study was designed to examine the effect of environmental enrichment during methamphetamine (METH) dependency and withdrawal on methamphetamine-induced spatial learning and memory deficits and obsessive-compulsive behavior. Method: Adult male Wistar rats (200 ± 10 g) chronically received bi-daily doses of METH (2 mg/kg, sc, with 12 hours intervals) for 14 days. Rats reared in standard (SE) or enriched environment (EE) during the development of dependence on METH and withdrawal. Then, they were tested for spatial learning and memory (the water maze), and obsessive-compulsive behavior as grooming behavior in METH-withdrawn rats. Results: The results revealed that the Sal/EE and METH/EE rats reared in EE spent more time in the target zone on the water maze and displayed significantly increased proximity to the platform compared to their control groups. METH withdrawn rats reared in EE displayed less grooming behavior than METH/SE group. Conclusion: Our findings revealed...

Long (LMS) versus brief (BMS) daily separations of rat pups from their mothers have contrasting effects on their adult stress responses and maternal behavior by respectively decreasing and increasing licking received from their mothers. We hypothesized that LMS decreases pup licking in mothers by inducing learned helplessness, creating a depression-like state. We subjected postpartum rats to LMS (3 h), BMS (15 min) or no separation (NMS) on postpartum days 2-14. After weaning, mothers were given a forced swim test (FST). LMS mothers exhibited more immobility and fewer escape attempts than BMS or NMS mothers. These results suggest that LMS induces a depressionlike state, which may account for the reductions in maternal behavior seen in LMS mothers. Immobility in the FST is recognized as an animal model of depression. Therefore, LMS may be a model of maternal depression.

Adverse conditions during early life are a risk factor for stress-related diseases. How this early adversity induce long-term effects is not well understood, however there are several evidence that the stress hormones play a determining role. Here we will focus on evidence obtained from the long-term consequences of prolonged maternal separation procedures. The purpose of this article is to review the literature about the influence of early experiences on the hypothalamic-pituitaryadrenal (HPA) axis function and endocrine stress responses in rodents. Early experiences have long-term influences on the behavioral and endocrine responses to stress and the alterations depend mostly on environment conditions and the interaction between mother and offspring. In the rodent, brief periods of separation result in an attenuated adrenal response to stress (reduced secretion of corticosterone). In contrast, longer periods of separation result in an exaggerated response. Besides, it is known tha...

The wide-scale analysis of protein expression provides a powerful strategy for the molecular exploration of complex pathophysiological mechanisms, such as the response to antidepressants. Using a 2D proteomic approach we investigated the Flinders Sensitive Line (FSL), a genetically selected rat model of depression, and the control Flinders Resistant Line (FRL). To evaluate gene-environment interactions, FSL and FRL pups were separated from their mothers for 3 h (maternal separation, MS), as early-life trauma is considered an important antecedent of depression. All groups were treated with either escitalopram (Esc) admixed to food (25 mg/kg.d) or vehicle for 1 month. At the week 3, forced swim tests were performed. Protein extracts from prefrontal/frontal cortex and hippocampus were separated by 2D electrophoresis. Proteins displaying statistically significant differences in expression levels were identified by mass spectrometry. Immobility time values in the forced swim test were higher in FSL rats and reduced by antidepressant treatment. Moreover, the Esc-induced reduction in immobility time was not detected in MS rats. The impact of genetic background in response to Esc was specifically investigated here. Bioinformatics analyses highlighted gene ontology terms showing tighter associations with the modulated proteins. Esc modulated protein belonging to cytoskeleton organization in FSL ; carbohydrate metabolism and intracellular transport in FRL. Proteins differently modulated in the two strains after MS and Esc play a role in cytoskeleton organization, vesicle-mediated transport, apoptosis regulation and macromolecule catabolism. These findings suggest pathways involved in neuronal remodelling as molecular correlates of response to antidepressants in a model of vulnerability.

In the present study, we investigated the effect of repeated neonatal morphine exposure and/or maternal deprivation(MD) on the nociceptive response and central biomarkers' BDNF, IL-1β, and IL-4 levels at postnatal days 16(PND16), 30(PND30), and 60(PND60). At birth, the litters were standardized to contain 8 pups/dam (n = 58). From PND1 to PND10, the pups of the deprived groups were separated daily from their mothers for 3 h and divided into 5 groups: control(C), saline(S), morphine(M), deprived-saline(DS), and deprived-morphine (DM). The pups received subcutaneous injections of saline/morphine (5 μg) in the mid-scapular area between PND8 and PND14. Nociceptive responses were assessed by hot plate(HP) and tail-flick(TFL) tests and biomarker levels by ELISA. Thermal hyperalgesia(HP) was found in all assessments for the M, DS, and DM groups, and a decrease in nociceptive threshold(TFL) was found in the DS group at PND16; M and DM groups at PND30; and M, DS, and DM groups at PND60. There were interactions between treatment/deprivation/timepoint in all central biomarkers' levels. The current study indicates that neonatal exposure to morphine and MD, which occurs in the pediatric ICU, can alter the nociceptive and neuroinflammatory responses.

Family Nurture Intervention (FNI) is designed to facilitate affective connections between prematurely born infants and their mothers. At term age, prematurely born infants with FNI had robust increases in frontal brain activity. Promoting early nurturing interactions may improve neurobehavioral outcomes of preterm infants. Objective: To assess the impact of Family Nurture Intervention (FNI) on electroencephalogram (EEG) activity in preterm infants (26-34 weeks gestation). Methods: Two groups were tested in a single, level IV neonatal intensive care unit (NICU; standard care or standard care plus FNI) using a randomized controlled trial design. The intervention consists of sessions designed to achieve mutual calm and promote communication of affect between infants and their mothers throughout the NICU stay. EEG recordings were obtained from 134 infants during sleep at $35 and $40 weeks postmenstrual age (PMA). Regional brain activity (power) was computed for 10 frequency bands between 1 and 48 Hz in each of 125 electrodes. Results: Near to term age, compared to standard care infants, FNI infants showed robust increases in EEG power in the frontal polar region at frequencies 10 to 48 Hz (20% to 36% with p-values <0.0004). Effects were significant in both quiet and active sleep, regardless of gender, singleton-twin status, gestational age (26-30 or 30-35 weeks) or birth weight (<1500 or >1500 g). Conclusion: FNI leads to increased frontal brain activity during sleep, which other investigators find predictive of better neurobehavioral outcomes. Significance: FNI may be a practicable means of improving outcomes in preterm infants.

Early‐life stimulation (e.g. brief handling) attenuates the behavioral and neuroendocrine responses to stressors encountered in adulthood, particularly with respect to activation of hypothalamic‐pituitary‐adrenal (HPA) activity. In contrast, if neonates were subjected to a more severe stressor, such as protracted separation from the dam or exposure to an endotoxin, then the adult response to a stressor was exaggerated. These early‐life experiences program HPA functioning, including negative feedback derived from stimulation of hippocampal glucocorticoid receptors, and corticotropin‐releasing hormone (CRH) and arginine vasopressin (AVP) coexpression in PVN neurons, to modify the response to subsequent stressor experiences. The persistent variations of HPA activity observed in handled/stimulated animals may stem from alterations in dam–pup interactions (e.g. increased arched‐back feeding, licking, grooming). In addition genetic makeup is critical in determining stress reactivity. For ...

Adverse childhood experiences can lead to cognitive (performance and memory) and affective (reward, emotional, and social processing) deficits (Pechtel & Pizzagalli, 2011). Previous studies have shown that early-life stressors such as maternal separation (MS) during infancy can affect the neurobiological, behavioral, cognitive (Berman, Lott,

A sample of 75 primiparas in Athens, Greece were interviewed 3 days following birth (Tl) regarding their attitudes towards maternal grandmother participation in child care. A follow-up questionnaire measuring the same attitudes and maternal separation anxiety (MSA) was answered 3-8 months later 0'2). It was found that maternal grandmothers were going to assist in child care in 68% of the cases. Higher scores on the MSA subscale 'employment-related separation concerns' were obtained by all mothers who were not assisted in child care by the maternal grandmother and were highest among those mothers intending to work before the child was 1 year old. Mothers who intended to work as well as those who had a higher educational level had significantly lower scores on the MSA subscale 'maternal separation anxiety'. Overall, mothers expressed favourable attitudes towards maternal grandmother participation at T l and T2. Positive attitudes were especially observed among mothers who relied on grandmothers for child care.

UCC Library and UCC researchers have made this item openly available. Please let us know how this has helped you. Thanks! Title The enduring effects of early life stress on the microbiota-gut-brain axis are buffered by dietary supplementation with milk fat globule membrane and a prebiotic blend

Background: Early maternal separation may have long-lasting physiological effects on different organ systems. Although long-lasting effects of early maternal separation are mostly studied in connection with the development and function of the central nervous system hypothalamic-pituitary-adrenal axis, animal health, behaviour and productivity, there is a lack of information about its impacts on the reproductive system. In the dairy industry, calves are often separated from mothers 1 or 2 days after birth and are not nursed. In the present retrospective study based on data from an artificial insemination (AI) centre, we compared semen parameters and fertility in bulls that were separated from their mothers one day after birth with the semen parameters of bulls that remained with their mothers and were nursed for approximately 2 months. Semen parameters were followed in 3 consecutive years in 52 maternally separated and 22 nursed bulls. Results: Ejaculate volume and total sperm count in ejaculate were significantly higher in nursed bulls in comparison to maternally separated bulls at the age 25-36 and 37-48 months, but interestingly, not at the age 12-24 months, during the first year in the AI centre. Non-return rates did not differ between separated and nursed bulls. Conclusion: The results suggest that early maternal separation causes long-lasting effects on the functioning of the male reproductive system, evident by reduced production of semen in adult bulls. The data suggest that with a standard of 20 million sperms per straw of frozen semen, 27-78 fewer straws can be obtained from one ejaculate of maternally separated bulls in comparison to the nursed bulls.

BACKGROUND AND OBJECTIVE: Deprivation of maternal care as a stressor causes disruption in cognitive and neurochemical activities of the brain. The aim of this study was to evaluation the effect of deprivation of maternal care on LTP induction in neurons of hippocampal CA1 region in morphine-dependent rats. METHODS: This experimental study was conducted among 40 45-day-old male rats in control group, morphinedependent group, and 3 groups of rats that were deprived of treatment for one, two and three weeks after birth for 3 hours daily. Except for the control group, the rest of the groups received 10 mg/kg body weight morphine sulfate subcutaneously every 12 hours for 10 days. On the eleventh day, the symptoms of deprivation syndrome were investigated by the Gellert-Holtzman method, and on the following day, the synaptic plasticity of neurons in CA1 region was studied. FINDINGS: The Gellert-Holtzman score in the morphine-dependent group was 14.98±4.16 and increased to 31.79±5.12 in th...

Childhood maltreatment, which can take the form of physical or psychological abuse, is experienced by more than a quarter of all children. Early life stress has substantial and long-term consequences, including an increased risk of drug abuse and psychiatric disorders in adolescence and adulthood, and this risk is higher in women than in men. The neuronal mechanisms underlying the influence of early life adversities on brain functioning remain poorly understood; therefore, in the current study, we used maternal separation (MS), a rodent model of earlylife neglect, to verify its influence on the properties of neurons in the ventral tegmental area (VTA), a brain area critically involved in reward and motivation processing. Using whole-cell patch-clamp recordings in brain slices from adolescent female Sprague-Dawley rats, we found an MS-induced increase in the excitability of putative dopaminergic (DAergic) neurons selectively in the medial part of the VTA. We also showed an enhancement of excitatory synaptic transmission in VTA putative DAergic neurons. MS-induced alterations in electrophysiology were accompanied by an increase in the diameter of dendritic spine heads on lateral VTA DAergic neurons, although the overall dendritic spine density remained unchanged. Finally, we reported MS-related increases in basal plasma ACTH and corticosterone levels. These results show the long-term consequences of early life stress and indicate the possible neuronal mechanisms of behavioral disturbances in individuals who experience early life neglect.

h i g h l i g h t s Family Nurture Intervention (FNI) is designed to facilitate affective connections between prematurely born infants and their mothers. At term age, prematurely born infants with FNI had robust increases in frontal brain activity. Promoting early nurturing interactions may improve neurobehavioral outcomes of preterm infants. a b s t r a c t Objective: To assess the impact of Family Nurture Intervention (FNI) on electroencephalogram (EEG) activity in preterm infants (26-34 weeks gestation). Methods: Two groups were tested in a single, level IV neonatal intensive care unit (NICU; standard care or standard care plus FNI) using a randomized controlled trial design. The intervention consists of sessions designed to achieve mutual calm and promote communication of affect between infants and their mothers throughout the NICU stay. EEG recordings were obtained from 134 infants during sleep at $35 and $40 weeks postmenstrual age (PMA). Regional brain activity (power) was computed for 10 frequency bands between 1 and 48 Hz in each of 125 electrodes. Results: Near to term age, compared to standard care infants, FNI infants showed robust increases in EEG power in the frontal polar region at frequencies 10 to 48 Hz (20% to 36% with p-values <0.0004). Effects were significant in both quiet and active sleep, regardless of gender, singleton-twin status, gestational age (26-30 or 30-35 weeks) or birth weight (<1500 or >1500 g). Conclusion: FNI leads to increased frontal brain activity during sleep, which other investigators find predictive of better neurobehavioral outcomes. Significance: FNI may be a practicable means of improving outcomes in preterm infants.

Early life stress is thought to contribute to psychiatric disorders, but the precise mechanisms underlying this link are poorly understood. As neonatal stress decreases adult hippocampal neurogenesis, which, in turn, functionally contributes to many behavioral phenotypes relevant to psychiatric disorders, we examined how in vivo neonatal maternal separation (NMS) impacts the capacity of adult hippocampal neural precursor cells via epigenetic alterations in vitro. Rat pups were separated from their dams for 3 hours daily from postnatal day (PND) 2 to PND 14 or were never separated from the dam (as control animals). We isolated adult neural precursor cells from the hippocampal dentate gyrus at PND 56 and assessed rates of proliferation, apoptosis, and differentiation in cell culture. We also evaluated the effect of DNA methylation at the retinoic acid receptor (RAR) promoter stemming from NMS on adult neural precursor cells. NMS attenuated neural differentiation of adult neural precur...

h i g h l i g h t s • Postpartum separations from their pups alter maternal behavior. • Mothers separated from their pups show memory impairment for both short and long-term memory. • Periodic mother-litter postpartum separation increases c-Fos expression in the CeA.

Early life experiences are crucial factors that shape brain development and function due to their ability to induce structural and functional plasticity. Among these experiences, early-life stress (ELS) is known to interfere with brain development and maturation, increasing the risk of future psychopathologies, including depression, anxiety, and personality disorders. Moreover, ELS may contribute to the emergence of these psychopathologies during adolescence. In this present study, we investigated the effects of ELS, in the form of maternal separation (MS), on the structural and functional plasticity of the medial prefrontal cortex (mPFC) and anxiety-like behavior in adolescent male rats. We found that the MS procedure resulted in disturbances in mother-pup interactions that lasted until weaning and were most strongly demonstrated by increases in nursing behavior. Moreover, MS caused atrophy of the basal dendritic tree and reduced spine density on both the apical and basal dendrites in layer II/III pyramidal neurons of the mPFC. The structural changes were accompanied by an impairment of long-term potentiation processes and increased expression of key proteins, specifically glutamate receptor 1, glutamate receptor 2, postsynaptic density protein 95, aCa 2+ /calmodulin-dependent protein kinase II and aCa 2+ /calmodulin-dependent protein kinase II phosphorylated at residue Thr305, that are engaged in long-term potentiation induction and maintenance in the mPFC. We also found that the MS animals were more anxious in the light/dark exploration test. The results of this study indicate that ELS has a significant impact on the structural and functional plasticity of the mPFC in adolescents. ELS-induced adaptive plasticity may underlie the pathomechanisms of some early-onset psychopathologies observed in adolescents.

h i g h l i g h t s • Maternal separation stress reduced both LTP and LTD at the thalamic input to the lateral amygdala. • Maternal separation stress impaired LTP and enhanced LTD at the cortical input to the lateral amygdala. • Treatment with imipramine restored the extent of the synaptic modification range at the thalamic input. • Treatment with imipramine restored the potential for LTD, but not for LTD, at the cortical input. • Imipramine-mediated restoration of synaptic plasticity will have consequences for amygdala-dependent learning.

This study analyzed ethanol intake in male and female Wistar rats exposed to maternal separation (MS) during infancy (postnatal days 1-21, PD1-21) and environmental enrichment (EE) during adolescence (PD 21-42). Previous work revealed that MS enhances ethanol consumption during adulthood. It is still unknown if a similar effect is found during adolescence. Several studies, in turn, have revealed that EE reverses stress experiences, and reduces ethanol consumption and reinforcement; although others reported greater ethanol intake after EE. The interactive effects between these treatments upon ethanol's effects and intake have yet to be explored. We assessed chronic ethanol intake and preference (12 two-bottle daily sessions, spread across 30 days, 1st session on PD46) in rats exposed to MS and EE. The main finding was that male-but not female-rats that had been exposed to EE consumed more ethanol than controls given standard housing, an effect that was not affected by MS. Subsequent experiments assessed several factors associated with heightened ethanol consumption in males exposed to MS and EE; namely taste aversive conditioning and hypnotic-sedative consequences of ethanol. We also measured anxiety response in the light-dark box and in the elevated plus maze tests; and exploratory patterns of novel stimuli and behaviors indicative of risk assessment and risk-taking, via a modified version of the concentric square field (CSF) test. Aversive conditioning, hypnosis and sleep time were similar in males exposed or not to EE. EE males, however, exhibited heightened exploration of novel stimuli and greater risk taking behaviors in the CSF test. It is likely that the promoting effect of EE upon ethanol intake was due to these effects upon exploratory and risk-taking behaviors.

h i g h l i g h t s Family Nurture Intervention (FNI) is designed to facilitate affective connections between prematurely born infants and their mothers. At term age, prematurely born infants with FNI had robust increases in frontal brain activity. Promoting early nurturing interactions may improve neurobehavioral outcomes of preterm infants. a b s t r a c t Objective: To assess the impact of Family Nurture Intervention (FNI) on electroencephalogram (EEG) activity in preterm infants (26-34 weeks gestation). Methods: Two groups were tested in a single, level IV neonatal intensive care unit (NICU; standard care or standard care plus FNI) using a randomized controlled trial design. The intervention consists of sessions designed to achieve mutual calm and promote communication of affect between infants and their mothers throughout the NICU stay. EEG recordings were obtained from 134 infants during sleep at $35 and $40 weeks postmenstrual age (PMA). Regional brain activity (power) was computed for 10 frequency bands between 1 and 48 Hz in each of 125 electrodes. Results: Near to term age, compared to standard care infants, FNI infants showed robust increases in EEG power in the frontal polar region at frequencies 10 to 48 Hz (20% to 36% with p-values <0.0004). Effects were significant in both quiet and active sleep, regardless of gender, singleton-twin status, gestational age (26-30 or 30-35 weeks) or birth weight (<1500 or >1500 g). Conclusion: FNI leads to increased frontal brain activity during sleep, which other investigators find predictive of better neurobehavioral outcomes. Significance: FNI may be a practicable means of improving outcomes in preterm infants.

Sex differences have been reported in the susceptibility to early life stress and its neurobiological correlates in humans and experimental animals. However, most of the current research with animal models of early stress has been performed mainly in males. In the present study, prolonged maternal separation (MS) paradigm was applied as an animal model to resemble the effects of adverse early experiences in male and female rats. Regional brain mitochondrial function, monoaminergic activity, and neuroinflammation were evaluated as adults. Mitochondrial energy metabolism was greatly decreased in MS females as compared with MS males in the prefrontal cortex, dorsal hippocampus, and the nucleus accumbens shell. In addition, MS males had lower serotonin levels and increased serotonin turnover in the prefrontal cortex and the hippocampus. However, MS females showed increased dopamine turnover in the prefrontal cortex and increased norepinephrine turnover in the striatum, but decreased dop...

fects of centrally administered corticotropin-releasing factor (CRF) and a-helical CRF on the vocalizations of isolated guinea pig pups. PHARMACOL BIOCHEM BEHAV 43(1)37-43, 1992.-Intraventricular corticotropin-releasing factor (CRF) was administered to guinea pig pups both with a freehand injection technique and via indwelling cannula. Behavioral effects depended upon the technique used. The highest dose of CRF (5 #g) inhibited the vocalizing of pups in a subsequent isolation test only when CRF was given by freehand injection. The possibility that disturbance attendant to the freehand procedure can account for this difference is discussed. To determine the effect of endogenous CRF in the absence of additional disturbance, the CRF antagonist t~-helical CRF (ahCRF) was administered with the indwelling cannula procedure, ahCRF enhanced vocalizing during the first 10 min, and enhanced locomotor activity during the last 10 rain, of a 30-min isolation test. Overall, the results indicate that endogenous CRF reduces vocalizing and locomotion during social isolation and that under certain injection conditions exogenous CRF can exacerbate the behavioral effect. The results also demonstrate the potential impact of the technique used to administer exogenous CRF. Further, the prevailing view, that CRF mediates stress-related behavioral responses, is supported only if behavioral inhibition, rather than vocalizing or locomotor activity, is viewed as the stress-related response in this situation. CRF t~-Helical CRF Maternal separation Isolation Vocalizations Cortisol Guinea pig

BACKGROUND AND OBJECTIVE: Deprivation of maternal care as a stressor causes disruption in cognitive and neurochemical activities of the brain. The aim of this study was to evaluation the effect of deprivation of maternal care on LTP induction in neurons of hippocampal CA1 region in morphine-dependent rats. METHODS: This experimental study was conducted among 40 45-day-old male rats in control group, morphinedependent group, and 3 groups of rats that were deprived of treatment for one, two and three weeks after birth for 3 hours daily. Except for the control group, the rest of the groups received 10 mg/kg body weight morphine sulfate subcutaneously every 12 hours for 10 days. On the eleventh day, the symptoms of deprivation syndrome were investigated by the Gellert-Holtzman method, and on the following day, the synaptic plasticity of neurons in CA1 region was studied. FINDINGS: The Gellert-Holtzman score in the morphine-dependent group was 14.98±4.16 and increased to 31.79±5.12 in th...

Although most available antidepressants increase monoaminergic neurotransmission, their therapeutic efficacy is likely mediated by longer-term molecular adaptations. To investigate the molecular changes induced by chronic antidepressant treatment we analysed proteomic changes in rat pre-frontal/frontal cortex and hippocampus after nortriptyline (NT) administration. A wide-scale analysis of protein expression was performed on the Flinders Sensitive Line (FSL), a genetically-selected rat model of depression, and the control Flinders Resistant Line (FRL). The effect of NT treatment was examined in a gene-environment interaction model, applying maternal separation (MS) to both strains. In the forced swim test, FSL rats were significantly more immobile than FRL animals, whereas NT treatment reduced immobility time. MS alone did not modify immobility time, but it impaired the response to NT in the FSL strain. In the proteomic analysis, in FSL rats NT treatment chiefly modulated cytoskeleton proteins and carbohydrate metabolism. In the FRL strain, changes influenced protein polymerization and intracellular transport. After MS, NT treatment mainly affected proteins in nucleotide metabolism in FSL rats and synaptic transmission and neurite morphogenesis pathways in FRL rats. When the effects of NT treatment and MS were compared between strains, carbohydrate metabolic pathways were predominantly modulated.

The medial prefrontal cortex (mPFC) is a key area for the regulation of numerous brain functions including stress response and cognitive processes. This brain area is also particularly affected by adversity during early life. Using an animal model in rats, we recently demonstrated that maternal exposure to a high-fat diet (HFD) prevents maternal separation (MS)-induced gene expression alterations in the developing PFC and attenuates several long-term deleterious behavioral effects of MS. In the present study, we ask whether maternal HFD could protect mPFC neurons of pups exposed to early life stress by examining dendritic morphology and spine density in juvenile [postnatal day (PND) 21] and adult rats submitted to MS. Dams were fed either a control or an HFD throughout gestation and lactation, and pups were submitted to MS from PND2 to PND14. We report that maternal HFD prevents MS-induced spine loss at PND21 and dendritic atrophy at adulthood. Furthermore, we show in adult MS rats ...

h i g h l i g h t s Family Nurture Intervention (FNI) is designed to facilitate affective connections between prematurely born infants and their mothers. At term age, prematurely born infants with FNI had robust increases in frontal brain activity. Promoting early nurturing interactions may improve neurobehavioral outcomes of preterm infants. a b s t r a c t Objective: To assess the impact of Family Nurture Intervention (FNI) on electroencephalogram (EEG) activity in preterm infants (26-34 weeks gestation). Methods: Two groups were tested in a single, level IV neonatal intensive care unit (NICU; standard care or standard care plus FNI) using a randomized controlled trial design. The intervention consists of sessions designed to achieve mutual calm and promote communication of affect between infants and their mothers throughout the NICU stay. EEG recordings were obtained from 134 infants during sleep at $35 and $40 weeks postmenstrual age (PMA). Regional brain activity (power) was computed for 10 frequency bands between 1 and 48 Hz in each of 125 electrodes. Results: Near to term age, compared to standard care infants, FNI infants showed robust increases in EEG power in the frontal polar region at frequencies 10 to 48 Hz (20% to 36% with p-values <0.0004). Effects were significant in both quiet and active sleep, regardless of gender, singleton-twin status, gestational age (26-30 or 30-35 weeks) or birth weight (<1500 or >1500 g). Conclusion: FNI leads to increased frontal brain activity during sleep, which other investigators find predictive of better neurobehavioral outcomes. Significance: FNI may be a practicable means of improving outcomes in preterm infants.

Objective: Prolonged maternal separation (PMS) in the first 2 wk of life has been associated with poor growth with lasting effects in brain structure and function. This study aimed to investigate whether PMS-induced undernutrition could cause systemic inflammation and changes in nutrition-related hormonal levels, affecting hippocampal structure and neurotransmission in C57BL/6J suckling mice. Methods: This study assessed mouse growth parameters coupled with insulin-like growth factor-1 (IGF-1) serum levels. In addition, leptin, adiponectin, and corticosterone serum levels were measured following PMS. Hippocampal stereology and the amino acid levels were also assessed. Furthermore, we measured myelin basic protein and synapthophysin (SYN) expression in the overall brain tissue and hippocampal SYN immunolabeling. For behavioral tests, we analyzed the ontogeny of selected neonatal reflexes. PMS was induced by separating half the pups in each litter from their lactating dams for defined periods each day (4 h on day 1, 8 h on day 2, and 12 h thereafter). A total of 67 suckling pups were used in this study. Results: PMS induced significant slowdown in weight gain and growth impairment. Significant reductions in serum leptin and IGF-1 levels were found following PMS. Total CA3 area and volume were reduced, specifically affecting the pyramidal layer in PMS mice. CA1 pyramidal layer area was also reduced. Overall hippocampal SYN immunolabeling was lower, especially in CA3 field and

Stress is an adaptive response to demands of the environment and thus essential for survival. Exposure to stress during the first years of life has been shown to have profound effects on the growth and development of an adult individual. There are evidences demonstrating that stressful experiences during gestation or in early life can lead to enhanced susceptibility to mental disorders. Early-life stress triggers hypothalamic-pituitary-adrenocortical (HPA) axis activation and the associated neurochemical reactions following glucocorticoid release are accompanied by a rapid physiological response. An excessive response may affect the developing brain resulting in neurobehavioral and neurochemical changes later in life. This article reviews the data from experimental studies aimed to investigate hormonal, functional, molecular and epigenetic mechanisms involved in the stress response during early-life programming. We think these studies might prove useful for the identification of novel pharmacological targets for more effective treatments of mental disorders.

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Childhood maltreatment, which can take the form of physical or psychological abuse, is experienced by more than a quarter of all children. Early life stress has substantial and long-term consequences, including an increased risk of drug abuse and psychiatric disorders in adolescence and adulthood, and this risk is higher in women than in men. The neuronal mechanisms underlying the influence of early life adversities on brain functioning remain poorly understood; therefore, in the current study, we used maternal separation (MS), a rodent model of earlylife neglect, to verify its influence on the properties of neurons in the ventral tegmental area (VTA), a brain area critically involved in reward and motivation processing. Using whole-cell patch-clamp recordings in brain slices from adolescent female Sprague-Dawley rats, we found an MS-induced increase in the excitability of putative dopaminergic (DAergic) neurons selectively in the medial part of the VTA. We also showed an enhancement of excitatory synaptic transmission in VTA putative DAergic neurons. MS-induced alterations in electrophysiology were accompanied by an increase in the diameter of dendritic spine heads on lateral VTA DAergic neurons, although the overall dendritic spine density remained unchanged. Finally, we reported MS-related increases in basal plasma ACTH and corticosterone levels. These results show the long-term consequences of early life stress and indicate the possible neuronal mechanisms of behavioral disturbances in individuals who experience early life neglect.

Introduction: Natural rewards are essential for survival. However, drug-seeking behaviors can be maladaptive and endanger survival. The present study was conducted to enhance our understanding of how animals respond to food and morphine as natural and drug rewards, respectively, in a conditioned place preference (CPP) paradigm.
Methods: We designed a protocol to induce food CPP and compare it as a natural reward with morphine CPP in rats. The protocol for reward induction in both groups (foods and morphine) consisted of three phases: pre-test, conditioning, and post-test. In morphine groups, we injected morphine as a reward (5 mg/kg, SC). To induce natural reward, we used two different protocols. In the first one, the rats were deprived of food for 24 h. In the other method, the rats were restricted to food for 14 days. During the conditioning period, the animals received daily chow, biscuits, or popcorn as a reward inducer.
Results: Results revealed that CPP was not induced in food-deprived rats. A combination of food restriction (as a facilitator) and a biscuit or popcorn-induced reward using CPP. In contrast, food deprivation did not facilitate food CPP in response to regular food. Interestingly the CPP score of the group which received biscuits during a 7-day conditioning period was more than that of the morphine group.
Conclusion: In conclusion, food restriction could be a better protocol than food deprivation to facilitate food reward.

h i g h l i g h t s We examined whether environmental enrichment (EE) could compensate the effects of early maternal separation (MS). Maternal separation impaired inhibitory avoidance but had no effect in object recognition. Grooming behavior in the open field was significantly lower in maternally separated animals. EE reversed the effects of MS in the inhibitory avoidance task and in grooming behavior. c-Fos expression as well as glucocorticoid receptor in the hippocampus were increased by enrichment.

BACKGROUND AND OBJECTIVE: Deprivation of maternal care as a stressor causes disruption in cognitive and neurochemical activities of the brain. The aim of this study was to evaluation the effect of deprivation of maternal care on LTP induction in neurons of hippocampal CA1 region in morphine-dependent rats.
METHODS: This experimental study was conducted among 40 45-day-old male rats in control group, morphine-dependent group, and 3 groups of rats that were deprived of treatment for one, two and three weeks after birth for 3 hours daily. Except for the control group, the rest of the groups received 10 mg/kg body weight morphine sulfate subcutaneously every 12 hours for 10 days. On the eleventh day, the symptoms of deprivation syndrome were investigated by the Gellert-Holtzman method, and on the following day, the synaptic plasticity of neurons in CA1 region was studied.
FINDINGS: The Gellert-Holtzman score in the morphine-dependent group was 14.98±4.16 and increased to 31.79±5.12 in the group that was deprived of maternal treatment for 3 weeks (p<0.001). Although morphine dependence did not affect basic responses of CA1 region neurons and LTP induction, deprivation of maternal care reduced the range of basic responses from 1.01±0.04 in the morphine-dependent group to 0.68±0.09 mV in the group that was deprived of maternal care for 3 weeks (p<0.001) and prevented LTP induction (p<0.001) in a time-dependent manner. 
CONCLUSION: The results of the study showed that deprivation of maternal care undermines the postsynaptic potential of the hippocampal CA1 region following morphine administration and disrupts the synaptic plasticity of the neurons in this region.

Objective: Prolonged maternal separation (PMS) in the first 2 wk of life has been associated with poor growth with lasting effects in brain structure and function. This study aimed to investigate whether PMS-induced undernutrition could cause systemic inflammation and changes in nutrition-related hormonal levels, affecting hippocampal structure and neurotransmission in C57BL/6J suckling mice. Methods: This study assessed mouse growth parameters coupled with insulin-like growth factor-1 (IGF-1) serum levels. In addition, leptin, adiponectin, and corticosterone serum levels were measured following PMS. Hippocampal stereology and the amino acid levels were also assessed. Furthermore, we measured myelin basic protein and synapthophysin (SYN) expression in the overall brain tissue and hippocampal SYN immunolabeling. For behavioral tests, we analyzed the ontogeny of selected neonatal reflexes. PMS was induced by separating half the pups in each litter from their lactating dams for defined periods each day (4 h on day 1, 8 h on day 2, and 12 h thereafter). A total of 67 suckling pups were used in this study. Results: PMS induced significant slowdown in weight gain and growth impairment. Significant reductions in serum leptin and IGF-1 levels were found following PMS. Total CA3 area and volume were reduced, specifically affecting the pyramidal layer in PMS mice. CA1 pyramidal layer area was also reduced. Overall hippocampal SYN immunolabeling was lower, especially in CA3 field and

Although most available antidepressants increase monoaminergic neurotransmission, their therapeutic efficacy is likely mediated by longer-term molecular adaptations. To investigate the molecular changes induced by chronic antidepressant treatment we analysed proteomic changes in rat pre-frontal/frontal cortex and hippocampus after nortriptyline (NT) administration. A wide-scale analysis of protein expression was performed on the Flinders Sensitive Line (FSL), a genetically-selected rat model of depression, and the control Flinders Resistant Line (FRL). The effect of NT treatment was examined in a gene-environment interaction model, applying maternal separation (MS) to both strains. In the forced swim test, FSL rats were significantly more immobile than FRL animals, whereas NT treatment reduced immobility time. MS alone did not modify immobility time, but it impaired the response to NT in the FSL strain. In the proteomic analysis, in FSL rats NT treatment chiefly modulated cytoskeleton proteins and carbohydrate metabolism. In the FRL strain, changes influenced protein polymerization and intracellular transport. After MS, NT treatment mainly affected proteins in nucleotide metabolism in FSL rats and synaptic transmission and neurite morphogenesis pathways in FRL rats. When the effects of NT treatment and MS were compared between strains, carbohydrate metabolic pathways were predominantly modulated.

Previous studies have highlighted interactions between serotonergic systems and adverse early life experience as important gene x environment determinants of risk of stress-related psychiatric disorders. Evidence suggests that mice deficient in Tph2, the rate-limiting enzyme for brain serotonin synthesis, display disruptions in behavioral phenotypes relevant to stress-related psychiatric disorders. The aim of this study was to determine how maternal separation in wildtype, heterozygous, and Tph2 knockout mice affects mRNA expression of serotonin-related genes. Serotonergic genes studied included Tph2, the high-affinity, low-capacity, sodium-dependent serotonin transporter (Slc6a4), the serotonin type 1a receptor (Htr1a), and the corticosterone-*

Nikolaos Daskalakis NURTURING NATURE. Testing the three-hit hypothesis of schizophrenia NURTURING NATURE Testing the three-hit hypothesis of schizophrenia Nikolaos Daskalakis Nikolaos P. Daskalakis (Νικόλαος Δασκαλάκης του Περικλέους Δασκαλάκη και της Σοφίας Αγαπουλάκη) was born in Athens (Greece), on October 7th, 1982. He attended high school at the Varvakeio High School (Βαρβάκειο Πειραματικό Γυμνάσιο) and graduated with summa cum laude in 2000. In the same year, he started studying Medicine, under scholarship, at the

The first 2 weeks of life are a critical period for neural development in rats. Repeated long-term separation from the dam is considered to be one of the most potent stressors to which rat pups can be exposed, and permanently modifies neurobiological and behavioral parameters. Prolonged periods of maternal separation (MS) usually increase stress reactivity during adulthood, and enhance anxiety-like behavior. The aim of this study was to verify the effects of maternal separation during the neonatal period on memory as well as on biochemical parameters (Na ? , K ?-ATPase and antioxidant enzymes activities) in the amygdala of adult rats. Females and male Wistar rats were subjected to repeated maternal separation (incubator at 32°C, 3 h/day) during postnatal days 1-10. At 60 days of age, the subjects were exposed to a Contextual fear conditioning task. One week after the behavioral task, animals were sacrificed and the amygdala was dissected for evaluation of Na ? , K ?-ATPase and antioxidant enzymes activities. Student-t test showed significant MS effect, causing an increase of freezing time in the three exposures to the aversive context in both sexes. Considering biochemical parameters Student-t test showed significant MS effect causing an increase of Na ? , K ?-ATPase activity in both sexes. On the other hand, no differences were found among the groups on the antioxidant enzymes activities [superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT)] in male rats, but in females, we found a significant MS effect, causing an increase of CAT activity and no differences were found among the groups on SOD and GPx activities. Our results suggest a role of early rearing environment in programming fear learning and memory in adulthood. An early stress experience such as maternal separation may increase activity in the amygdala (as pointed by the increased activity of Na ? , K ?-ATPase), affecting behaviors related to fear in adulthood, and this effect could be task-specific.

Family Nurture Intervention (FNI) is designed to facilitate affective connections between prematurely born infants and their mothers. At term age, prematurely born infants with FNI had robust increases in frontal brain activity. Promoting early nurturing interactions may improve neurobehavioral outcomes of preterm infants. Objective: To assess the impact of Family Nurture Intervention (FNI) on electroencephalogram (EEG) activity in preterm infants (26-34 weeks gestation). Methods: Two groups were tested in a single, level IV neonatal intensive care unit (NICU; standard care or standard care plus FNI) using a randomized controlled trial design. The intervention consists of sessions designed to achieve mutual calm and promote communication of affect between infants and their mothers throughout the NICU stay. EEG recordings were obtained from 134 infants during sleep at $35 and $40 weeks postmenstrual age (PMA). Regional brain activity (power) was computed for 10 frequency bands between 1 and 48 Hz in each of 125 electrodes. Results: Near to term age, compared to standard care infants, FNI infants showed robust increases in EEG power in the frontal polar region at frequencies 10 to 48 Hz (20% to 36% with p-values <0.0004). Effects were significant in both quiet and active sleep, regardless of gender, singleton-twin status, gestational age (26-30 or 30-35 weeks) or birth weight (<1500 or >1500 g). Conclusion: FNI leads to increased frontal brain activity during sleep, which other investigators find predictive of better neurobehavioral outcomes. Significance: FNI may be a practicable means of improving outcomes in preterm infants.

The mother-child relationship is fundamental to the establishment and maintenance of synaptic networks and physiological and emotional development. Animal models including maternal separation have been used to study changes at behavioral and neurobiochemical levels. Due to the relevance of glial cells during development, our aim was to determine if short periods of maternal separation during breastfeeding induce permanent changes in a number of astrocytes labeled with the glial fibrillary acidic protein in different brain areas. Wistar rats were housed under standard laboratory conditions with reversed light/dark cycle; food and water ad libitum. Pups were separated from their mothers for 6 h daily during breastfeeding period. On day 22, pups were separately housed according to gender and treatment. At day 60, subjects were evaluated in the elevated plus maze and, after processing for immunohistochemistry, 20-μm sections were made. Prefrontal cortex, paraventricular nucleus, preoptic area, hippocampus and amygdala were localized. Labeled cells were quantified using Image-J program. Results showed that separated females had more entries into open arms and spend more time as compared with the control groups. In the prefrontal cortex we identified a decrease in staining cells in separated females, whereas there was an increase in staining cells in separated males. In the hippocampus and preoptic area, we observed a decrease only in separated males. We did not find any differences in the paraventricular nucleus or amygdala. Our results indicate that maternal separation during breastfeeding induces permanent changes in the number of astrocytes in different brain areas of both males and females.

This research paper focuses on experimental investigation on composite column subjected to cyclic loading was used for proper experimental work & analytical analysis of CFST columns were carried out. CFST column structure has high ductility , high load bearing capacity hence it has been widely used in civil engineering field. In this work experiment were carried for cfst column with infill of light weight concrete were used.. Experimental on circularly cyclic loaded composite steel tubes were also carried out for different length , width of varying thickness. Ultimate load values obtained were compared with analytical results. The experiment was a carried for different L/D ratio for different grade of concrete that is M20,M30 & M40

h i g h l i g h t s Family Nurture Intervention (FNI) is designed to facilitate affective connections between prematurely born infants and their mothers. At term age, prematurely born infants with FNI had robust increases in frontal brain activity. Promoting early nurturing interactions may improve neurobehavioral outcomes of preterm infants. a b s t r a c t Objective: To assess the impact of Family Nurture Intervention (FNI) on electroencephalogram (EEG) activity in preterm infants (26-34 weeks gestation). Methods: Two groups were tested in a single, level IV neonatal intensive care unit (NICU; standard care or standard care plus FNI) using a randomized controlled trial design. The intervention consists of sessions designed to achieve mutual calm and promote communication of affect between infants and their mothers throughout the NICU stay. EEG recordings were obtained from 134 infants during sleep at $35 and $40 weeks postmenstrual age (PMA). Regional brain activity (power) was computed for 10 frequency bands between 1 and 48 Hz in each of 125 electrodes. Results: Near to term age, compared to standard care infants, FNI infants showed robust increases in EEG power in the frontal polar region at frequencies 10 to 48 Hz (20% to 36% with p-values <0.0004). Effects were significant in both quiet and active sleep, regardless of gender, singleton-twin status, gestational age (26-30 or 30-35 weeks) or birth weight (<1500 or >1500 g). Conclusion: FNI leads to increased frontal brain activity during sleep, which other investigators find predictive of better neurobehavioral outcomes. Significance: FNI may be a practicable means of improving outcomes in preterm infants.