Maternal Deprivation Research Articles

Maternal deprivation induces persistent adaptations in putative dopamine neurons in rat ventral tegmental area: in vivo electrophysiological study.

Early life aversive experiences can trigger persistent deficits in neuronal signaling within the mesolimbic pathway, most notably in the dopamine (DA) neurons of the ventral tegmental area (VTA). The identity of such cellular mechanisms currently appears as an important issue. To address this concern, we investigated whether early life maternal deprivation (MD) would affect the electrical activity of VTA DA neurons, via in vivo extracellular single-unit recording. Male Wistar rats were deprived of their dams for 3h per day from postnatal days (PND) 1-14. Thereafter, the adult animals (PND 70-80) were tested for the discharge activity of putative VTA DA neurons. The VTA DA neurons displayed a decrease in firing rate and an increase in the variability of baseline discharge activity in deprived animals. MD also caused a decrease in burst firing of VTA DA neurons compared to control subjects. In summary, early life MD induces a hypoactive VTA DA system, which may contribute to lifespan psychopathologies.

Stress-Induced Cognitive Impairments: A Narrative Systematic Review

Stress is multifactorial, acting via the hypothalamo-pituitary-adrenal axis; with its mediator’s receptors present in the brain’s cognition control area. We identified the causative stressors, ameliorating interventions and patho-physiological mechanisms of stress-induced cognitive-impairments in Medline via a systematic review of PubMed™ using search keywords: ‘stress*’, ‘cogniti*’, ‘executive function’, ‘memory’, ‘learning’ and ‘impairment’, limited in time to 2009 and later, yielding 2795 papers on March 23rd, 2017, reduced to 197 after removing duplicates and reviewing the titles for appropriateness, followed by review of the articles using a-priori criteria. Perceived stress showed no gender disparity, although financial stress was significant in women like work-stress in men. Marriage conferred more stress on women. Acute and/or chronic stress affects learning, memory, attention and executive function cognitive domains. Stressors causing cognitive-impairments include prenatal stress, maternal deprivation, childhood maltreatment, anaesthesia, chronic immobilization, chronic social defeat, illness, noise, sleep deprivation and trauma. Exercise, environmental enrichment and NSAIDS reduce stress-induced cognitive-impairment. Implicated patho-physiological mechanisms include cyclo-oxygenase-2, cholinergic muscarinic and µ-opioid receptors. Newer pathophysiologic mechanisms support future research.

Physical exercise enhances vulnerability to migraine headache associated with CGRP up-expression in trigeminal nucleus caudalis of stressed rats

ABSTRACT Objectives There is conflicting evidence on the effect of physical exercise on migraine development. Present study investigated the impact of treadmill exercise on migraine – associated symptoms and changes in calcitonin gene-related peptide (CGRP) expression in rats with and without maternal deprivation stress (MD). Methods Two days after birth, the male Wistar pups were randomly divided into four groups (n = 6) as follows: intact, exercise, MD, and MD plus exercise. The animals in the MD groups were separated from their dams 4 h per day for 2 weeks. At 8 weeks of age, the rats were exercised on a motor-driven treadmill for 4 weeks. Then, nitroglycerin (NTG) (5 mg/kg/IP) was used to induce migraine and pain-related symptoms were recorded for 90 min. NTG-related thermal hyperalgesia was measured by tail flick and hot plate methods. Finally, immunofluorescence staining of CGRP in trigeminal subnucleus caudalis (Vc) was performed. Results NTG – produced a significant headache symptoms and thermal hypersensitivity, which were aggravated following physical exercise in stressed or unstressed groups. Besides, NTG administration increased CGRP expression in the Vc of rats. Such effect was overpowered by treadmill running only in rats exposed to MD stress. Conclusion These findings highlight the worsening effects of treadmill exercise for migraine in rats with and without MD stress. However, inflammatory response can further exacerbate in stressed rats.

Differential effects of two early life stress paradigms on cerebellar-dependent delay eyeblink conditioning

Early life stress paradigms have become prominent in the animal literature to model atypical development. Currently, two models have prevailed within the literature: (1) limited bedding or nesting and (2) maternal separation or deprivation. Both models have produced aberrations spanning behavior and neural circuitry. Surprisingly, these two models have yet to be directly compared. The current study utilized delay eyeblink conditioning, an associative learning task with a well-defined cerebellar circuit, to compare the behavioral effects of standard limited bedding (postnatal day 2–9, n = 15) and maternal separation (60 min per day during postnatal day 2–14, n = 13) early life stress paradigms. Animals in all groups exhibited robust learning curves. Surprisingly, facilitated conditioning was observed in the maternal separation group. Rats that underwent limited bedding did not differ from the control or maternal separation groups on any conditioning measures. This study contributes to a clearer understanding of early life stress paradigms and the claims made about their mechanisms, which if better clarified can be properly leveraged to increase translational value.

On the role of the dopaminergic system in the memory deficits induced by maternal deprivation

Previous researches showed that maternal deprivation (MD) leads to memory deficits that persist until adulthood. The hippocampus, an important brain structure involved in memory processes, receives dopaminergic afferents from other brain areas that modulate memory. Here we demonstrated that MD results in object recognition memory deficits that are reverted by intra-hippocampal stimulation of D1-dopaminergic receptor and peripheral administration of a dopamine precursor. The D1-dopaminergic receptor and peripheral administration of a dopamine precursor also promoted memory persistence in control rats.

Effects of sleep modulation during pregnancy in the mother and offspring: Evidences from preclinical research.

Disturbed sleep during gestation may lead to adverse outcomes for both mother and child. Animal research plays an important role in providing insights into this research field by enabling ethical and methodological requirements that are not possible in humans. Here, we present an overview and discuss the main research findings related to the effects of prenatal sleep deprivation in animal models. Using systematic review approaches, we retrieved 42 articles dealing with some type of sleep alteration. The most frequent research topics in this context were maternal sleep deprivation, maternal behaviour, offspring behaviour, development of sleep-wake cycles in the offspring, hippocampal neurodevelopment, pregnancy viability, renal physiology, hypertension and metabolism. This overview indicates that the number of basic studies in this field is growing, and provides biological plausibility to suggest that sleep disturbances might be detrimental to both mother and offspring by promoting increased risk at the behavioural, hormonal, electrophysiological, metabolic and epigenetic levels. More studies on the effects of maternal sleep deprivation are needed, in light of their major translational perspective.

Social subordination induced by early life adversity rewires inhibitory control of the prefrontal cortex via enhanced Npy1r signaling

Social hierarchies are present in most mammalian species. In nature, hierarchies offer a tradeoff between reduction of in-group fighting between males, at the expense of an asymmetric sharing of resources. Early life experiences and stress are known to influence the rank an individual attains in adulthood, but the associated cellular and synaptic alterations are poorly understood. Using a maternal separation protocol, we show that care-deprived mice display a long-lasting submissive phenotype, increased social recognition, and enhanced explorative behavior. These alterations are consistent with an adaptation that favors exploration rather than confrontation within a group setting. At the neuronal level, these animals display dendritic atrophy and enhanced inhibitory synaptic inputs in medial prefrontal cortex (mPFC) neurons. To determine what could underlie this synaptic modification, we first assessed global gene expression changes via RNAseq, and next focused on a smaller subset of putatively altered synaptic receptors that could explain the changes in synaptic inhibition. Using different cohorts of maternally deprived mice, we validated a significant increase in the expression of Npy1r, a receptor known to play a role in maternal care, anxiety, foraging, and regulation of group behavior. Using electrophysiological recordings in adult mice while blocking NPY1R signaling, we determined that this receptor plays a key role in enhancing GABAergic currents in mice that experience maternal deprivation. Taken together, our work highlights the potential of regulating NPY1R in social anxiety disorders and the alterations induced in brain circuitry as a consequence of early life stress and adversity.

Offspring reverse transcriptome responses to maternal deprivation when reared with pathogens in an insect with facultative family life.

Offspring of species with facultative family life are able to live with and without parents (i.e. to adjust to extreme changes in their social environment). While these adjustments are well understood on a phenotypic level, their genetic underpinnings remain surprisingly understudied. Investigating gene expression changes in response to parental absence may elucidate the genetic constraints driving evolutionary transitions between solitary and family life. Here, we manipulated maternal presence to observe gene expression changes in the fat body of juvenile European earwigs, an insect with facultative family life. Because parents typically protect offspring against pathogens, expression changes were recorded in pathogen-free and pathogen-exposed environments. We found that manipulating maternal presence changed the expression of 154 genes, including several metabolism and growth-related genes, and that this change depended on pathogen presence. Specifically, localization and cell transporter genes were downregulated in maternal absence without pathogens but upregulated with pathogens. At least one immunity gene (pathogenesis-related protein 5) was affected by pathogen exposure regardless of maternal presence. Overall, our findings explicate how offspring adjust to parental deprivation on a molecular level and reveal that such adjustments heavily depend on pathogens in the environment. This emphasizes the central role of pathogens in family life evolution.

Emotional Distress in the Relationship of Caregivers and Institutionalized Babies.

Institutionalization is an exceptional and temporary measure that occurs when there is a violation of rights; lasting until the family reintegration or, in the impossibility of this, the placement in a substitute family through adoption. Among the main reasons for institutionalization in Brazil are the financial difficulties, abandonment, domestic violence, drug addiction, homelessness of the responsible for the child, sexual abuse, and the loss of parents by death or imprisonment. Although children and adolescents have their rights assured when they are institutionalized, the care provided in these spaces does not include all their needs and demands, which may damage their affective-relational development. Maternal deprivation in the first years of life can be detrimental to the development of these children, if not provided by adequate substitute care. Therefore, to understand which place the institutionalized baby occupies in the imaginary of the social caregivers and, from this, how is established the relationship regarding the care, is of fundamental importance to assess and address the risk factors in child development at this stage of life and in situation of institutionalization. This is an exploratory and descriptive study, developed in a childcare institution, located in the city of São Paulo, Brazil, capable of accommodating up to 20 babies between 0 and 2 years old. Data collection was performed with nine employees, eight social caregivers and one general service assistant who work directly in the care of the institutionalized babies. Drawing-Story with Theme (DS-T) procedures were used. Qualitative analysis was based on Interpretative Phenomenological Analysis. The appreciation of the nine applied Drawing-Story procedures allowed the establishment of three discussion axes representations of baby, baby care, and early separation process. This study concluded that the difficulties that permeate the context of caregivers’ work are the high turnover of institutionalized children, as well as employees, the difficulty of dealing with processes of bonding and breaking bonds and no recognition of the profession. We highlight that the place that these babies occupy in the imaginary of these caregivers influences the bond they establish with the children hence the care offered to the babies. It is also noteworthy that these caregivers exhibited anguish and suffering from the reasons they believed led the children to be institutionalized.

Stressor and Multi‐Organ Antioxidant Profile following Early Life Maternal Deprivation in Albino Rats

One‐week‐old albino pups were separated from their dams for a period of 24 to 48 hours. Sixty (60) rats were divided into 6 equal groups (n=10). Group A rats were separated for 24 hours and given glucose subcutaneously (200mg/kg) at 2, 7, 12 and 22 hours post maternal deprivation (MD). Group B rats received no intervention or treatment. Group C was subjected to 24 hours MD and given distilled water at regular intervals as group A. Group D rats had no MD but were given distilled water at same intervals as group A. Groups E and F were subjected to 48‐hour MD and administered Glucose or distilled water respectively at 2, 7, 17, 22, 27, 32, 42 and 47 hours post MD. Blood and tissue samples were collected for biochemical analyses.Significant weight gains were recorded in the groups with no maternal deprivation. The 48‐hour MD group supplemented with glucose competed favorably, showing a 7.2% weight gain over two days. At the other end of the spectrum, the 24‐hour MD supplemented with distilled water group recorded a 3% weight loss.The results show a graded rise in brain total protein values with time, with the highest values recorded in the 48‐hour MD + distilled water group and the lowest in the 24‐hour MD + distilled water group. Other organs showed no significant differences between groups. There were no differences across groups in all the organs assayed for nitric oxide (NO) either. For specific oxidative stress markers, Brain malondialdehyde (MDA) levels appear to be significantly lowest at the 48‐hour MD + distilled water group when compared with other groups. This correlated with a time dependent depletion in the brain antioxidant enzyme profiles studied. Brain GST, GPX and SOD all show highest concentrations in the 24‐hour MD + glucose group with lowest values recorded in the 48‐hour MD + distilled water group. Other organs did not show marked differences in between groups.Cortisol levels were assayed to evaluate stressor responses. The highest concentrations were seen in the 48‐hour MD + glucose group with the least seen in the 24‐hour MD + distilled water group. Consequently, parenteral administration of fluids (water and glucose) are a poor substitute for maternal nutrition although initial evidence points towards potential decline in brain antioxidant profile.Support or Funding InformationThe Tertiary Education Trust Fund (TETFUND) of Nigeria. The Faculty of Veterinary Medicine, University of Abuja, Nigeria.The Cardiorenal research group, Faculty of Veterinary Medicine, University of Ibadan; especially Professor Adeolu A. Adedapo, Dr. Tayo O. Omobowale, Dr. Ademola A. Oyagbemi and Dr. Jerry Afolabi.Brain Total Protein (TP) and Malondialdehyde (MDA) charts of all the groupsFigure 1

Impact of Maternal Sleep Deprivation and Caffeine Consumption on Neurodevelopmental and Behavioural Outcomes in Young Rats

Caffeine is a neurostimulant, which has been shown to be both cognitive‐enhancing and sleep‐disrupting. Several reports agree that caffeine and sleep deprivation have opposing effects on behaviours, including cogntive and depressive behaviours. Therefore, this study was designed to evaluate the neurodevelopmental and behavioural outcomes following prenatal and postnatal caffeine treatment and chronic sleep deprivation in rats. Pregnant Long‐Evans rats were sleep‐deprived 8 h/day in the last trimester of gestation using the platform‐over‐water sleep deprivation model; and treated orally with 120 mg/kg of caffeine from gestation day 8 and throughout lactation. Learning and memory, social, anxiety‐like and depressive‐like behaviours were assessed in the prepubescent rats (Postnatal Date 35). The young rats exhibited a higher anxiety level, as revealed by higher open field entry frequencies. They performed poorly in the novel object recognition test, and displayed abnormal sociability and social novelty in the social tests. Additionally, there was decreased hippocampal serotonergic activity and a marked reduction in synaptic protein expression in the CA1 hippocampal region, the prefrontal cortex and amygdala. Taken together, this study suggests that prenatal and postnatal sleep deprivation and caffeine consumption can interfere with brain development and thus impact behavioural outcomes, which could increase susceptibility to neurological disorders in adulthood.

Mother-daughter relationship among women with psychogenic infertility: psychological-psychoanalytical perspective

The subject of this research is the mother-daughter relationship and the image of a mother among women with psychogenic infertility. The object of this research is the child-parent relationship in women’s development. There is a small number of studies that indirectly confirm the correlation between distressed relationship of a woman with her mother in childhood and the genesis of psychogenic infertility. Women with psychogenic infertility usually had conflicting, ambivalent and unstable relationships with their mother in childhood, particularly in puberty period. Often, the image of the mother is subconsciously imprinted in woman’s psyche, affects her stance on motherhood, even if this image has nothing in common with the actual relationship in the dyad. This article describes the aspect of proneness to conflict and aggression in mother-daughter relationship among women with psychogenic infertility. The novelty of this research consists in formulation of a theoretical model of development (psychogenesis) of mother-daughter relationship among women with psychogenic infertility from psychoanalytical perspective. One of the elements of such model are the hostile and conflicting mother-daughter relationship among women with psychogenic infertility. The acquired results demonstrate that women with psychogenic infertility consider their mothers averse and less accepting than women without such disorder. They perceive their mother as showing enough emotions, care and love, or have memories of hostility and aggression towards them in childhood. Women with psychogenic infertility were impacted by lack of maternal attention than women without this disorder. Women with psychogenic infertility are characterized with avoidance and ambivalent type of affection for their mother and are more likely to view maternal deprivation as an unfair circumstance in life.

Histone deacetylase inhibition reduces ventral tegmental area dopamine neuronal hyperexcitability involving AKAP150 signaling following maternal deprivation in juvenile male rats.

Traumatic early life stress (ELS) is linked to dopamine (DA) dysregulation which increases the probability of developing psychiatric disorders in adolescence and adulthood. Our prior studies demonstrated that a severe early life stressor, a 24-hr maternal deprivation (MD) in juvenile male rats, could lead to altered DA signaling from the ventral tegmental area (VTA) due to impairment of GABAergic synaptic plasticity (promoting GABAergic long-term depression, LTD) with concomitant changes in the abundance of synaptic regulators including A-kinase anchoring protein (AKAP150). Importantly, these MD-induced synaptic changes in the VTA were accompanied by upregulation of histone deacetylase 2, histone hypoacetylation, and were reversible by HDAC inhibition. Using cell-attached and whole-cell patch clamp recordings, we found that MD stress also increased spontaneous VTA DA neuronal activity and excitability in juvenile male rats without affecting intrinsic excitability. Postsynaptic chemical disruption of AKAP150 and protein kinase A interaction increased VTA DA neuronal excitability in control non-MD rats mimicking the effects of MD on DA cell excitability with similar changes in membrane properties. Interestingly, this disruption decreased MD-induced VTA DA hyperexcitability. This MD-induced DA neuronal hyperexcitability could also be normalized at 24hr after injection of the class 1 HDAC inhibitor, CI-994. Altogether, our data suggest that AKAP150 plays a critical role in the regulation of VTA DA neuronal excitability and that HDAC-mediated targeting of AKAP150 signaling could normalize VTA DA dysfunction following ELS thereby providing novel therapeutic targets for prevention of later life psychopathology.

On the Nature of the Mother-Infant Tie and Its Interaction With Freudian Drives.

The affective bond between an infant and its caregiver, the so-called mother-infant tie, was analyzed by various reputable psychologists (e.g., Ainsworth, Clark, Erikson, Anna Freud, Harlow, Klein, Spitz, and Winnicott) but both the basic tenets of the bond and the importance of the trauma of maternal deprivation for personality disorders in adults were introduced by Bowlby. Although Bowlby was a trained psychoanalyst, he rejected central cornerstones of Freudian theory (esp. drive theory) and used concepts promulgated by renowned ethologists (Tinbergen and Lorenz) to establish his framework of “instinctive behavior” that has been developed further into the concept of “attachment theory” under the influence of Mary Ainsworth. However, since any precise experimental facts were lacking when Bowlby formulated his ideas on the concept of instinctive behavior, the whole framework is a descriptive, category-driven approach (like the ones of Freudian drives). In order to connect the mother-infant tie – as propounded by Bowlby – with experimental data, this manuscript undertakes a biochemical analysis of it because this strategy proved somewhat successful in relation to Freudian drives. The analysis unfolded that the neurochemical oxytocin, released by the action of sensory nerves, is of utmost importance for the operation of the mother-infant tie. Furthermore, multiple evidences have been presented to the fact that there is strong interaction between unconsciously operating Freudian drives and the consciously acting mother-infant tie (that is now classified as a drive). The outlined interaction in conjunction with the classification of attachment urges as drives gave a very detailed insight into how a SEEKING-derived reward can be evoked during operation of the mother-infant tie. In summary, there is no need to marginalize either the mother-infant tie or Freudian drives but rather there is need to respect both (principally different) impulses in moving toward a more extensive description.

Early Life Stress Increases Brain Glutamate and Induces Neurobehavioral Manifestations in Rats

Background: Early life stress (ELS) is associated with an increased risk of developing depression and anxiety disorders. Disturbances of the neurobiological glutamatergic system are implicated in depression; however, the long-term effects of early life stress on glutamate (Glu) metabolites remain unclear. Our study used 7T proton magnetic resonance spectroscopy (7T 1 HMRS) to detect metabolic Glu in a rat model to investigate maternal deprivation (MD)-induced ELS. Methods: MD was established in Sprague-Dawley rats by periodic separation from mothers and peers. Changes in the hippocampal volume and Glu metabolism were detected by 7T 1 HMRS after testing for depression-like behavior via open field, sucrose preference, and Morris water maze tests. Findings: Adult MD offspring exhibited depression-like behavior. Compared to control, the MD group exhibited reduced ratio of central activity time to total time and decreased sucrose consumption (18 ± 6 g vs. 31 ± 12 g, p = 0·02). MD rats spent less time in the fourth quadrant, where the platform was originally placed, in the Morris water maze test. According to 7T 1 HMRS, MD rats had elevated Glu and glutamate+glutamine (Glu+Gln) levels compared with the control group hippocampi, but Gln and gamma-aminobutyric acid (GABA), glutamate+glutamine (Glu+Gln) in the prefrontal cortex of MD rats showed a downward trend. Interpretation: Depression-like behavior and cognition deficits related to ELS may induce region-specific changes in Glu metabolism in the prefrontal cortex and hippocampus. The novel, noninvasive 7T 1 HMRS-identified associations between Glu levels and ELS may guide future clinical studies. Funding Statement: The Key Program of the National Natural Science Foundation of China, No. 30930027; Program of the National Natural Science Foundation of China, No. 60971075; Natural Science Foundation of Guangdong Province of China, Nos.S2011010005194 and 2015A030313444; Shantou University Scientific Research Foundation for the Doctoral Scholar of China, No.NTF10010; The Department of Education, Guangdong Government under the Top-tier University Development Scheme for Research and Control of Infectious Diseases of China, No. 2015034. Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics Approval Statement: All procedures used in the study were reviewed and approved by the Ethics Committee of School of Medicine, Shantou University Medical College, and comply with the National Institutes of Health’s Guide for the Care and Use of Laboratory Animals (NIH publication no. 85-23, revised 1985). In the handling and care of all animals, we followed the international guiding principles for animal research, as stipulated by the World Health Organization (WHO) Chronicle (World Health Organization, 1985), as adopted by the Laboratory Animal Center, Shantou University Medical College.

Pioglitazone alleviates maternal sleep deprivation-induced cognitive deficits in male rat offspring by enhancing microglia-mediated neurogenesis

Maternal sleep disturbance in pregnancy causes cognitive impairments and emotional disorders in offspring. Microglia-mediated inflammatory processes contribute to prenatal stress-induced neurodevelopmental deficits. Peroxisome proliferator-activated receptor gamma (PPARγ) activation underlies the switching of microglial activation phenotypes, which has emerged as a pharmacological target for regulating neuroinflammatory responses in the treatment of neuropsychiatric disorders. Here we investigated the effects of PPARγ-dependent microglial activation on neurogenesis and cognitive behavioral outcomes in male rat offspring exposed to maternal sleep deprivation (MSD) for 72 h from days 18–21 of pregnancy. In the Morris water maze test, male MSD rat offspring needed more time than control offspring to escape to the hidden platform and spent less time in the target quadrant when the hidden platform was removed. In MSD rat offspring, microglial density as determined by immunofluorescence was higher, microglia showed fewer and shorter processes, and neurogenesis in the hippocampus was significantly reduced. Levels of mRNA encoding pro-inflammatory markers IL-6, TNFα, and IL-1β were higher in male MSD offspring, whereas levels of anti-inflammatory markers Arg1, IL-4, and IL-10 were lower, as was PPARγ expression in the hippocampus. PPARγ activation by pioglitazone (30 mg/kg/day, i.p., 7 d) mitigated these negative effects of MSD, rescuing hippocampal neurogenesis and improving cognitive function. The PPARγ inhibitor GW9662 (1 mg/kg/day, i.p., 7 d) eliminated the effects of pioglitazone. Conditioned medium from pioglitazone-treated microglia promoted proliferation and differentiation of neural progenitor cells. These results suggest that MSD-induced deficits in spatial learning and memory can be ameliorated through PPARγ-dependent modulation of microglial phenotypes.

Early Maternal and Social Deprivation Expands Neural Stem Cell Population Size and Reduces Hippocampus/Amygdala-Dependent Fear Memory.

Early life stress can exert detrimental or beneficial effects on neural development and postnatal behavior depending on the timing, duration, strength, and ability to control the stressors. In this study, we utilized a maternal and social deprivation (MSD) model to investigate the effects of early life stress on neural stem cells (NSCs) and neurogenesis in the adult brain. We found that MSD during the stress-hyporesponsive period (SHRP) (early-MSD), when corticosterone secretion is suppressed, increased the size of the NSC population, whereas the same stress beyond the SHRP abrogated these effects. Early-MSD enhanced neurogenesis not only in the dentate gyrus of the hippocampus, one of the classic neurogenic regions, but also in the amygdala. In addition, mice exposed to early-MSD exhibited a reduction in amygdala/hippocampus-dependent fear memory. These results suggest that animals exposed to early life stress during the SHRP have reinforced stress resilience to cope with perceived stressors to maintain a normal homeostatic state.

Efecto de la exposición a ozono sobre un modelo de privación materna en ratas

El maltrato infantil es uno de los mayores problemas sociales y económicos a nivel mundial. Entre las personas que han sido víctimas del MI existe una alta prevalencia de violencia, abuso de drogas y enfermedades psiquiátricas, entre otros. A nivel fisiológico, el eje hipotálamo-pituitaria-adrenal y la respuesta al estrés están directamente relacionados con esta prevalencia. Además, en los últimos años, ha aumentado la preocupación por el efecto de la contaminación sobre la salud humana. El objetivo de este proyecto es determinar el efecto de la exposición crónica a un ambiente contaminado con ozono, sobre algunos biomarcadores, en un modelo animal de privación materna. Se medirá cómo afecta la exposición a ozono sobre la capacidad cognitiva y el estado de ansiedad. Además, se analizará la variación de corticosterona y ACTH en plasma tras la exposición a un estresor agudo. Por último, se analizará el volumen del hipocampo y sus subáreas, así como el grado de metilación del exón promotor del receptor de glucocorticoides 1F y del exón promotor de vasopresina. Con el presente trabajo se pretende ampliar el conocimiento sobre el desarrollo cognitivo de niños que han sufrido maltrato infantil.

Maternal deprivation impairs memory and cognitive flexibility, effect that is avoided by environmental enrichment

Maternal deprivation (MD) causes cognitive deficits that persist until adulthood. Thereby, the environmental enrichment (EE) is widely used to increase brain plasticity. Here, pregnant female rats were used and their offspring were submitted to neonatal MD from post-natal day 1–10; after weaning the rats were submitted to EE. MD caused deficits on short and long-term aversive and recognition memory and on cognitive flexibility tested on reversed Morris Water Maze test. MD also promoted the decrease of hippocampal Brain-Derived Neurotropic Factor (BDNF) protein expression. The EE was able to protect against the cognitive deficits, avoiding the memory and the cognitive flexibility disrupting, and normalizing hippocampal BDNF expression of rats submitted to MD. These data confirms that MD promotes long-life memory deficits and demonstrates that MD causes cognitive flexibility disruption; the mechanisms seem involve the decrease of BDNF. We also demonstrate that EE, which improves BDNF, is able to avoid memory deficits and cognitive flexibility disrupts.

Maternal Deprivation and Sex Alter Central Levels of Neurotrophins and Inflammatory Cytokines in Rats Exposed to Palatable Food in Adolescence

Maternal deprivation (MD) in rodents is used to simulate human-infant early life stress, which leads to neural, hormonal, and behavioral alterations. Palatable food (PF) can reduce the stress response, and individuals use it as a self-applied stress relief method. Thus, the present study aimed to evaluate the effect of the association between MD in the early life (P1–P10) and PF consumption (condensed milk, P21–P44) in the central neuroplasticity (BDNF/NGF levels) and central neuroinflammatory parameters (TNF-α, IL-6, and IL-10 levels) in male and female Wistar rats in the adolescence. In addition, weight-related parameters (weight gain, Lee Index, and relative adipose tissue weight) were evaluated. PF exposure increased relative adipose tissue weight; however, it did not lead to a change in animals’ body weight. MD reduced hypothalamic BDNF and NGF levels, and hippocampal TNF-α levels in male and female rats. Animals of both sexes that received PF, exhibited reduced hypothalamic NGF levels. Neuroinflammatory marker evaluations showed that male rats were more susceptible to the interventions than female rats, since MD reduced their cortical IL-10 levels and PF increased their IL-6 levels. Differences in the Lee index, central BDNF, TNF-α, and IL-6levels were observed between sexes. Male animals per se presented greater Lee index. Female rats had higher BDNF and IL-6 levels in the hippocampus and hypothalamus and higher hypothalamic TNF-α levels than those observed in males. In conclusion, there were more noticeable effects of MD than PF on the variables measured in this study. Sex effect was identified as an important factor and influenced most of the neurochemical measures in this study. In this way, we suggest including both female and male animals in researches to improve the quality of translational studies.