scholarly journals Sex Differences in the Brain-Blood Barrier in Rats Exposed to Early life Stress and the Treatment with Antidepressants and Psychobiotic

2021 ◽  
Author(s):  
Maria Eduarda M. Botelho ◽  
Anelise S. Carlessi ◽  
Luana M. Manosso ◽  
Laura A. Borba ◽  
Airam B. de Moura ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Life Stress ◽  
Early Life Stress ◽  
Maternal Deprivation ◽  
Female Rats ◽  
Male Rats ◽  
Major Depressive ◽  
Male And Female Rats ◽  
The Brain ◽  
Age And Sex

Abstract Major depressive disorder is a debilitating mental disorder. Although the etiology is not fully understood, the impairment to the blood-brain barrier (BBB) integrity may be involved. Maternal deprivation was performed in the first 10 postnatal days for 3h/day. Male and female rats were divided into control and maternal deprivation. Maternal deprivation animals were subdivided and received treatment with saline, escitalopram, ketamine, or probiotic. The integrity of BBB was evaluated in the prefrontal cortex and hippocampus at postnatal days 11, 21, 41, and 61. Maternal deprivation caused BBB breakdown in the prefrontal cortex and hippocampus in female and male rats in all ages evaluated, except in the prefrontal cortex of females at postnatal day 41. In females, escitalopram, ketamine, and probiotic reversed BBB breakdown in all ages evaluated, except probiotic at postnatal day 21 (prefrontal cortex), and ketamine at postnatal days 21 and 41 (hippocampus). In males, escitalopram, ketamine, and probiotic reversed BBB breakdown in the prefrontal cortex in all ages evaluated, except escitalopram at postnatal days 41 and 61. In the hippocampus of males, BBB damage was reversed by escitalopram at postnatal day 21 and ketamine at postnatal day 41. Treatment with escitalopram, ketamine, or probiotics can prevent changes in the BBB integrity, depending on the age and sex of the animal. Clinically it is important to evaluate different treatments depending on age and sex.

scholarly journals Early-Life Stress Modulates Gut Microbiota and Peripheral and Central Inflammation in a Sex-Dependent Manner

2021 ◽  
Vol 22 (4) ◽  
pp. 1899 ◽  
Author(s):  
Hae Jeong Park ◽  
Sang A. Kim ◽  
Won Sub Kang ◽  
Jong Woo Kim
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Female Rats ◽  
Rrna Gene ◽  
Dependent Manner ◽  
Male And Female Rats

Recent studies have reported that changes in gut microbiota composition could induce neuropsychiatric problems. In this study, we investigated alterations in gut microbiota induced by early-life stress (ELS) in rats subjected to maternal separation (MS; 6 h a day, postnatal days (PNDs) 1–21), along with changes in inflammatory cytokines and tryptophan-kynurenine (TRP-KYN) metabolism, and assessed the differences between sexes. High-throughput sequencing of the bacterial 16S rRNA gene showed that the relative abundance of the Bacteroides genus was increased and that of the Lachnospiraceae family was decreased in the feces of MS rats of both sexes (PND 56). By comparison, MS increased the relative abundance of the Streptococcus genus and decreased that of the Staphylococcus genus only in males, whereas the abundance of the Sporobacter genus was enhanced and that of the Mucispirillum genus was reduced by MS only in females. In addition, the levels of proinflammatory cytokines were increased in the colons (IFN-γ and IL-6) and sera (IL-1β) of the male MS rats, together with the elevation of the KYN/TRP ratio in the sera, but not in females. In the hippocampus, MS elevated the level of IL-1β and the KYN/TRP ratio in both male and female rats. These results indicate that MS induces peripheral and central inflammation and TRP-KYN metabolism in a sex-dependent manner, together with sex-specific changes in gut microbes.

scholarly journals Effects of Maternal Deprivation on Anxiety, Depression, and Empathy in Male and Female Offspring of Wistar Rats in the Face of Novel Objects

2019 ◽  
Vol 8 ◽  
pp. 1093
Author(s):  
Solmaz Khalifeh ◽  
Fariba Khodagholi ◽  
Mehrad Moghtadaei ◽  
Ali Behvarmanesh ◽  
Afshin Kheradmand ◽  
...  
Keyword(s):  
Life Stress ◽  
Wistar Rats ◽  
Female Offspring ◽  
Maternal Deprivation ◽  
Female Rats ◽  
Control Group ◽  
Male And Female ◽  
Male And Female Rats ◽  
Novel Objects ◽  
Anxiety Depression

Background: Early life stress (ELS) models such as maternal deprivation (MD) are used to in¬vestigate behavioral changes in rodents under stressful situations. MD is a situation in which rat pups are separated from the dam; MD has different paradigms. The purpose of this research is to evaluate the effects of maternal deprivation on anxiety, depression, and empathy in adult Wistar rats. Materials and Methods: MD was applied to pups as per specifically designed protocol to compare rats of the control group with maternal deprivation rats and also the group, which faced novel objects. Each group consisted of eight rats. In this study, separation started from postnatal day (PND) 14 for various periods up to PND 60. EPM test was undertaken to measure anxiety; moreover, FST was used to indicate levels of depression. Also, changes in the empathy ratio were also demonstrated. One-way analysis of variance (ANOVA), Tukey’s post hoc analysis, and t-test were applied to analyze the results. Results: MD-treated rats showed a significant decrease in anxiety and empathy indexes compared with those in the control group (P<0.05). However, MD significantly increased depression in both male and female rats (P<0.05). Final¬ly, exposure to novel objects decreased depression but did not have any effect on anxiety and empathy levels in MD rats (P<0.05). Conclusion: ELS may lead to various states of mood and behavior in adulthood. According to the findings of this study, depression increases due to MD, though both anxiety and empathy decrease in both male and female Wistar rats. Moreover, ex¬posure to novel objects decreases depression, while anxiety and empathy do not change signifi¬cantly with exposure to novel objects. [GMJ.2019;8:e1093]

Abstract 17: Early Life Stress Sensitizes The Angiotensin II-elicited Hypertensive Response

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Baojian Xue ◽  
Terry Beltz ◽  
Fang Guo ◽  
David M Pollock ◽  
Jennifer S Pollock ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Proinflammatory Cytokines ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Male Rats ◽  
Sprague Dawley ◽  
Cns Inflammation ◽  
Wide Range ◽  
The Brain

Separation of neonatal rodent pups from their mothers has been used as a model to study the effects of early life stress (ELS) on behavioral and physiological responses in adults. Using an Induction-Delay-Expression experimental paradigm, our previous studies demonstrate that a wide range of stressors administered during an induction period produces hypertensive response sensitization (HTRS) in response to a subsequent pro-hypertensive stimulus. HTRS is accompanied by activation of the brain renin-angiotensin system (RAS) and CNS inflammation. The present study investigated whether ELS induces HTRS and changes in brain-related underlying mechanisms. Rat neonates from Sprague-Dawley breeders were subjected to ELS by separating them each morning from their mothers for 3 h on postnatal days 2 to 14. Pups from non-handled litters formed control groups. At 10 weeks of age, male rats were used to evaluate blood pressure and autonomic function using telemetric probes and pharmacological methods. In addition, in separate control and ELS groups, the lamina terminalis (LT) structures and the hypothalamic paraventricular nucleus (PVN) were analyzed for mRNA expression of RAS components and proinflammatory cytokines. Adult ELS rats as compared to non-separated controls exhibited 1) HTRS during expression testing using 2 week ANG II infusions (120 ng/kg/min s.c.; ELS animals, Δ45.5±4.5 mmHg vs. controls, Δ22.4±3.1 mmHg); 2) a greater reduction in mean arterial pressure following ganglionic blockade (hexamethonium, 30 mg/kg, ip), 3) increased sympathetic drive to the heart (atenolol, 8 mg/kg, ip), 4) decreased vagal tone (atropine, 8 mg/kg, ip), and 5) increased mRNA expression of several components of the brain RAS and proinflammatory cytokines in the LT and PVN. These results suggest that maternal ELS may predispose individuals to hypertension that is mediated by upregulation of the brain RAS and proinflammatory cytokines and increased sympathetic drive to the cardiovascular system.

scholarly journals Sex-Specific Effects of Early Life Stress on Brain Mitochondrial Function, Monoamine Levels and Neuroinflammation

2020 ◽  
Vol 10 (7) ◽  
pp. 447 ◽  
Author(s):  
Héctor González-Pardo ◽  
Jorge L. Arias ◽  
Eneritz Gómez-Lázaro ◽  
Isabel López Taboada ◽  
Nélida M. Conejo
Keyword(s):  
Sex Differences ◽  
Prefrontal Cortex ◽  
Mitochondrial Function ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Female Rats ◽  
Dopamine Turnover ◽  
Mitochondrial Energy Metabolism ◽  
Brain Mitochondrial Function

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 dopamine turnover in the hippocampus. Sex differences were also found for pro-inflammatory cytokine levels, with increased levels of TNF-α and IL-6 in the prefrontal cortex and hippocampus of MS males, and increased IL-6 levels in the striatum of MS females. These results evidence the complex sex- and brain region-specific long-term consequences of early life stress.

scholarly journals Postnatal treatment with metyrapone attenuates the effects of diet-induced obesity in female rats exposed to early-life stress

2017 ◽  
Vol 312 (2) ◽  
pp. E98-E108 ◽  
Author(s):  
Margaret O. Murphy ◽  
Joseph B. Herald ◽  
Caleb T. Wills ◽  
Stanley G. Unfried ◽  
Dianne M. Cohn ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Glucose Intolerance ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Diet Induced Obesity ◽  
Postnatal Treatment

Experimental studies in rodents have shown that females are more susceptible to exhibiting fat expansion and metabolic disease compared with males in several models of fetal programming. This study tested the hypothesis that female rat pups exposed to maternal separation (MatSep), a model of early-life stress, display an exacerbated response to diet-induced obesity compared with male rats. Also, we tested whether the postnatal treatment with metyrapone (MTP), a corticosterone synthase inhibitor, would attenuate this phenotype. MatSep was performed in WKY offspring by separation from the dam (3 h/day, postnatal days 2–14). Upon weaning, male and female rats were placed on a normal (ND; 18% kcal fat) or high-fat diet (HFD; 60% kcal fat). Nondisturbed littermates served as controls. In male rats, no diet-induced differences in body weight (BW), glucose tolerance, and fat tissue weight and morphology were found between MatSep and control male rats. However, female MatSep rats displayed increased BW gain, fat pad weights, and glucose intolerance compared with control rats ( P < 0.05). Also, HFD increased plasma corticosterone (196 ± 51 vs. 79 ± 18 pg/ml, P < 0.05) and leptin levels (1.8 ± 0.4 vs. 1.3 ± 0.1 ng/ml, P < 0.05) in female MatSep compared with control rats, whereas insulin and adiponectin levels were similar between groups. Female control and MatSep offspring were treated with MTP (50 µg/g ip) 30 min before the daily separation. MTP treatment significantly attenuated diet-induced obesity risk factors, including elevated adiposity, hyperleptinemia, and glucose intolerance. These findings show that exposure to stress hormones during early life could be a key event to enhance diet-induced obesity and metabolic disease in female rats. Thus, pharmacological and/or behavioral inflection of the stress levels is a potential therapeutic approach for prevention of early life stress-enhanced obesity and metabolic disease.

scholarly journals Adolescent cocaine induced persistent negative affect in female rats exposed to early-life stress

2021 ◽  
Author(s):  
Cristian Bis-Humbert ◽  
M. Julia García-Fuster
Keyword(s):  
Risk Factors ◽  
Negative Affect ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Maternal Deprivation ◽  
Female Rats ◽  
Suitable Model ◽  
The Impact ◽  
Early Drug

Abstract Rationale The combination of several risk factors (sex, a prior underlying psychiatric condition, or early drug initiation) could induce the emergence of negative affect during cocaine abstinence and increase the risk of developing addiction. However, most prior preclinical studies have been centered in male rodents, traditionally excluding females from these analyses. Objectives To ascertain the behavioral and neurochemical consequences of adolescent cocaine exposure when the combination of several risk factors is present (female, early-life stress). Methods Whole litters of Sprague–Dawley rats were exposed to maternal deprivation for 24 h on postnatal day (PND) 9. Cocaine was administered in adolescence (15 mg/kg/day, i.p., PND 33–39). Negative affect was assessed by several behavioral tests (forced swim, open field, novelty-suppressed feeding, sucrose preference). Hippocampal cell fate markers were evaluated by western blot (FADD, Bax, cytochrome c) or immunohistochemistry (Ki-67; cell proliferation). Results Maternal deprivation is a suitable model of psychiatric vulnerability in which to study the impact of adolescent cocaine in female rats. While adolescent cocaine did not alter affective-like behavior during adolescence, a pro-depressive–like state emerged during adulthood, exclusively in rats re-exposed to cocaine during abstinence. FADD regulation by cocaine in early-life stressed female rats might contribute to certain hippocampal neuroadaptations with some significance to the observed induced negative affect. Conclusions Adolescent cocaine induced persistent negative affect in female rats exposed to early-life stress, highlighting the risk of early drug initiation during adolescence for the emergence of negative reinforcement during abstinence likely driving cocaine addiction vulnerability, also in female rats.

scholarly journals Maternal Separation Induces Sex-Specific Differences in Sensitivity to Traumatic Stress

2021 ◽  
Vol 15 ◽  
Author(s):  
Dayan Knox ◽  
Stephanie A. Stout-Oswald ◽  
Melissa Tan ◽  
Sophie A. George ◽  
Israel Liberzon
Keyword(s):  
Risk Factors ◽  
Sex Differences ◽  
Animal Models ◽  
Traumatic Stress ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Female Rats ◽  
Male Rats

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder with a high economic burden. Two risk factors for increasing the chances of developing PTSD are sex (being female) and early life stress. These risk factors suggest that early life stress-induced changes and sex differences in emotional circuits and neuroendocrinological systems lead to susceptibility to traumatic stress. Exploring mechanisms via which stress leads to specific effects can be accomplished in animal models, but reliable animal models that allow for an examination of how early life stress interacts with sex to increase susceptibility to traumatic stress is lacking. To address this, we examined the effects of early life stress [using the maternal separation (MS) model] and late adolescence/early adult traumatic stress [using the single prolonged stress (SPS) model] on startle reactivity, anxiety-like behavior in the open field (OF), and basal corticosterone levels in male and female rats. Female rats exposed to MS and SPS (MS/SPS) showed enhanced startle reactivity relative to MS/control female rats. Enhanced startle reactivity was not observed in MS/SPS male rats. Instead, non-maternally separated male rats that were exposed to SPS showed enhanced startle reactivity relative to controls. Female rats had enhanced locomotor activity in the OF and higher basal corticosterone levels in comparison to males, but measures in the OF and basal corticosterone were not affected by MS or SPS. Overall the results suggest that the combined MS and SPS models can be used to explore how changes in maternal care during infancy lead to sex differences in sensitivity to the effects of traumatic stress as adolescents and adults.

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