Behavior Of Offspring Research Articles

Mechanisms of Transgenerational ‘Memory’ in Mice and Rats: A Review

Researchers have discovered that parental experiences and environment can affect offspring behaviors and phenotypes through non-genetic mechanisms in one or more generations among various animals. This phenomenon is most commonly studied in mice and rats, where different mechanisms are believed to exist due to the diverse inheritance patterns discovered with different parental experiences in the experiments, including stress, liver damage, odor fear conditioning, environmental enrichment (EE), etc. Besides the commonly known factor, social transmission, epigenetic modifications are also suggested to be a major cause, with DNA methylation, histone modification, and microRNA level change observed in different studies. The epigenetic marks are lost after certain generations, and they are found to be reversible due to environmental change. This non-genetic phenotypic response to environmental stimuli could benefit or harm offspring.

Elevated level of prenatal testosterone and vitamin D3 deficiency during pregnancy, in the presence of prenatal maternal stress, and their association with the development of attention deficit hyperactivity disorder (ADHD)-like symptoms in toddlers.

To investigate the hypothesis that the presence of prenatal maternal stress, increased level of prenatal testosterone, and low level of vitamin D3 in pregnancy is associated with the development of ADHD-like symptoms in toddlers (< 2 years old). The study group comprised 53 pregnant women and 53 infants of these pregnancies. The population cohort of 53 pregnant women were recruited at their 35th to 37th week of pregnancy and investigated prospectively. The participants were selected through targeted selection. Maternal experience of stressful life events was assessed by stress standardised questionnaires, prenatal testosterone was determined in the mothers' saliva by using the immune enzymatic (ELISA) method, and maternal plasma D vitamin was measured using the ECLIA method, during pregnancy. When the age of the offspring was 6 months and then less than 2 years, the mothers completed the child behaviour and temperament checklist. A small but statistically significant association was found between the common symptom complex of ADHD and the level of testosterone and vitamin D3, in the presence of prenatal maternal stress. Multiple regression analysis showed that maternal stressful events during pregnancy significantly predicted ADHD behaviours in offspring. The study supported the hypothesis that prenatal maternal stress, increased level of prenatal testosterone, and low level of vitamin D3 during pregnancy increases the risk of development of ADHD-like symptoms in toddlers (< 2 years old). Also, the obtained results support the hypothesis that the influence of prenatal factors causes ADHD-like symptoms in offspring through a programming effect.

Post-natal antibiotic exposure in mother rat (F0) induces anxiety like behavior in adult rat offspring (F1) by activating HPA axis and down-regulating the Nr3c1 gene.

Early postnatal administration of antibiotics has been linked to lasting effects on brain development and behavior. Research conducted on animals that are free from germs has demonstrated that the impact of microbiome colonization on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and neuroendocrine pathways is substantial, which play a crucial role in stress management. Nevertheless, it is still uncertain if the exposure to antibiotics in rat dams (F0-generation) before weaning is associated with neurobehavioral changes in rat offspring (F1-generation) during adulthood. In order to investigate the effects, we perturbed the intestinal microbiota of rat dams (F0 generation) by administering cefixime (CEF), an antibiotic commonly used for obstetric purposes, at clinically relevant doses (1 mg/kg, 2.5 mg/kg or 5 mg/kg). Anxiety-like behaviors in adult offspring was evaluated through the utilization of elevated plus maze (EPM) and open field paradigm (OFP) following a six-week interval from birth (PND42). Subsequent to behavioral assessments, the rats were euthanized, and their brains and blood was collected for biochemical analysis. Plasma corticosterone concentration was used to assess HPA activity, whereas the quantitative real-time polymerase chain reaction (PCR) was employed to determine the transcription levels of the glucocorticoid receptor (GR) Nr3c1. The offspring of F1 that were administered antibiotics before being weaned spent less time in the EPM open arm. The alterations were accompanied by increased levels of corticosterone in the bloodstream. The gene expression study revealed a decrease in the levels of mRNA transcription of Nr3c1. This research emphasizes the possible long-term effects of antibiotic exposure before weaning on the development of anxiety in offspring upon adulthood.

Juvenile exposure to low-level 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters behavior and longitudinal morphometrics in zebrafish and F1 offspring.

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental endocrine disruptor and model AhR agonist, is linked to skeletal abnormalities, cardiac edema, stunted growth rate, altered metabolism, and neurobehavioral deficits. We have previously reported transgenerational reproductive outcomes of developmental TCDD exposure in adult zebrafish (Danio rerio), an NIH-validated model for developmental and generational toxicology. Using the same paradigm of sublethal TCDD exposure (50 pg/ml) at both 3 and 7 weeks post fertilization (wpf), we investigated several novel endpoints, including longitudinal morphometrics and anxiety-linked behavior, in fish exposed as juveniles. We also assessed developmental abnormalities and neurobehavior in their F1 larval offspring. TCDD exposure induced timepoint-dependent decreases in several craniofacial and trunk morphometrics across juvenile development. In early adulthood, however, only exposed males underwent a transient period of compensatory growth, ending between 7 and 12 months post fertilization (mpf). At 12 mpf, exposed adult fish of both sexes displayed increased exploratory behaviors in a novel tank test. The F1 offspring of parents exposed at both 3 and 7 wpf were hyperactive, but neurobehavioral outcomes diverged depending on parental exposure window. F1 exposure-lineage larvae had increased rates of edema and skeletal abnormalities, but fewer unhatched larvae compared to controls. Parent- and timepoint-specific effects of exposure on abnormality rate were also evaluated; these outcomes were considerably less severe. Our novel behavioral findings expand current knowledge of the long-term and intergenerational consequences of early-life TCDD exposure in a zebrafish model, in addition to delineating minor longitudinal morphometric changes in exposed fish and abnormalities in larval offspring.

Improvement of autistic-like behaviors in adult rats prenatally exposed to valproic acid through early suppression of orexin receptor.

Autism spectrum disorder (ASD) is a disabling psychiatric disease characterized by impairments in communication and social skills. The pathophysiology of autism is complex and not fully known. Considering the incidence of sleep disorders in individuals with ASD and the important role of orexin in sleep, it is possible to hypothesize that an alteration of the orexinergic system could be implicated in the pathogenesis of autism symptoms. The present study was conducted to investigate the effect of suvorexant [dual orexin receptor antagonists (DORAs)] on autism-like behavior in prenatally valproic acid (VPA)-exposed rats]. Wistar female rats were administered VPA [600 mg/kg, intraperitoneally (i.p.)] or normal saline (10 ml/kg, i.p.; vehicle control) on gestational day 12.5. Thirty-two male offspring were divided into four groups: Control, VPA, Suvorexant+VPA, and VPA+Risperidone. The pups were given suvorexant [20 ml/kg, by mouth/orally (p.o.)] or risperidone (1 ml/kg, p.o.) daily from postnatal day (PND) (40-54). The offspring were tested for repetitive behaviors and cognitive ability with a Y-maze task on PND 55, and social interaction was assessed by play behavior in the open field on PND 56. And anxiety with using the three-chamber social assay on PND 56. In the Y-maze apparatus, spontaneous alteration significantly decreased in the prenatal VPA-treated rats compared to control rats showing autistic-like behavior, and 2-week suvorexant increased the alternation, indicating the beneficial effect of suvorexant. Prenatal treatment with VPA, impaired play behavior (sniffing, grooming, and darting), and increased anxiety-related behavior. Suvorexant treatment attenuated the problems in male offspring's social behavior. Our results showed that suvorexant improved ASD-associated behaviors in the VPA-treated rats, and the orexinergic system may be associated with the pathogenesis of autism symptoms.

Extraembryonic metabolism of corticosterone protects against effects of exposure

When females experience stress during reproduction, developing embryos can be exposed to elevated levels of glucocorticoids, which can permanently affect offspring development, physiology, and behavior. However, the embryo can regulate exposure to glucocorticoids. In placental species, the placenta regulates embryonic exposure to maternal steroids via metabolism. In a comparable way, recent evidence has shown the extraembryonic membranes of avian species also regulate embryonic exposure to a number of maternal steroids deposited in the yolk via metabolism early in development. However, despite the known effects of embryonic exposure to glucocorticoids, it is not yet understood how glucocorticoids are metabolized early in development. To address this knowledge gap, we injected corticosterone into freshly laid chicken (Gallus gallus) eggs and identified corticosterone metabolites, located metabolomic enzyme transcript expression, tracked metabolomic enzyme transcript expression during the first six days of development, and determined the effect of corticosterone and metabolites on embryonic survival. We found that yolk corticosterone was metabolized before day four of development into two metabolites: 5β-corticosterone and 20β-corticosterone. The enzymes, AKR1D1 and CBR1 respectively, were expressed in the extraembryonic membranes. Expression was dynamic during early development, peaking on day two of development. Finally, we found that corticosterone exposure is lethal to the embryos, yet exposure to the metabolites is not, suggesting that metabolism protects the embryo. Ultimately, we show that the extraembryonic membranes of avian species actively regulate their endocrine environment very early in development.

GluN2A Mediates PS-Induced Depressive-Like Behavior by Activating CaMKII and Inhibiting Myelinization.

Prenatal stress (PS) can induce depression in offspring, but the underlying mechanisms are still unknown. The aim of this work was to investigate the mechanism that underlies PS-induced depressive-like behavior in offspring. A prenatal restraint stress procedure was developed in which pregnant rats at GD14 to GD20 were placed head-first into a well-ventilated bottle three times each day and for 45 min each time. Depressive-like behavior in the male offspring was examined using the sucrose preference test (SPT) and the forced swim test (FST). The level of glutamate and the expression levels of GluN2A, p-CaMKII and myelin basic protein (MBP) in the hippocampus of PS-susceptible (PS-S) offspring were also evaluated. To clarify the mechanism by which PS leads to depression in offspring, the effects of excessive corticosterone were also investigated using an in vitro "injured neuronal" model. The glutamate level in the hippocampus of PS-S male offspring was significantly elevated compared to controls. The expression levels of GluN2A and p-CaMKII were also altered. In addition, the optical density of MBP staining and the expression levels of MBP mRNA and MBP protein were decreased, demonstrating impaired myelinization in the hippocampus. Treatment of PS-S offspring with the GluN2A receptor antagonist NVP-AAM077 resulted in antidepressant-like effects in the FST, as well as rescue of the MBP and p-CaMKII abnormalities. These findings indicate that GluN2A is a promising target in the development of pharmacotherapies for PS-induced depression.

Litter reduction-induced obesity promotes early depressive-like behavior and elevated prefrontal cortex GFAP expression in male offspring

AimsThe present study was developed to investigate how litter reduction-induced obesity promotes early depressive-related behaviors in rodent offspring. Main methodsWe employed a standardized litter size reduction protocol, dividing litters into groups: normal litters (NL), consisting of six males and six females pups and small litters (SL), comprising two males and two females pups. Maternal behavior was monitored during the initial week of lactation. Subsequently, we assessed the pups for weight gain, locomotor activity, social play behavior, and performance in forced swimming test. We further evaluated the weights of retroperitoneal and perigonadal fat tissues, along with the expression of glial fibrillary acidic pprotein (GFAP) in the hippocampus and prefrontal cortex of the offspring. Key findingsOur results indicated that litter size reduction led to an increased the maternal behavior. In contrast, offspring from the SL group displayed greater weight gain and increased, retroperitoneal and perigonadal fat. Both male and female rodents in the SL group exhibited decreased social play behavior, and male offspring spent more time immobile during the forced swimming test, suggesting a depressive-like phenotype. Notably, we observed an increase in the GFAP expression in the prefrontal cortex of male rodents, with a trend toward increased expression in the hippocampus. SignificanceObesity may facilitate the development of early depressive-like behaviors, potentially associated with elevated GFAP expression in the prefrontal cortex.

Maternal selenium dietary supplementation alters sociability and reinforcement learning deficits induced by in utero exposure to maternal immune activation in mice

Maternal immune activation (MIA) during pregnancy increases the risk for the unborn foetus to develop neurodevelopmental conditions such as autism spectrum disorder and schizophrenia later in life. MIA mouse models recapitulate behavioural and biological phenotypes relevant to both conditions, and are valuable models to test novel treatment approaches. Selenium (Se) has potent anti-inflammatory properties suggesting it may be an effective prophylactic treatment against MIA. The aim of this study was to determine if Se supplementation during pregnancy can prevent adverse effects of MIA on offspring brain and behaviour in a mouse model.Selenium was administered via drinking water (1.5 ppm) to pregnant dams from gestational day (GD) 9 to birth, and MIA was induced at GD17 using polyinosinic:polycytidylic acid (poly-I:C, 20 mg/kg via intraperitoneal injection). Foetal placenta and brain cytokine levels were assessed using a Luminex assay and brain elemental nutrients assessed using inductively coupled plasma- mass spectrometry. Adult offspring were behaviourally assessed using a reinforcement learning paradigm, the three-chamber sociability test and the open field test. MIA elevated placental IL-1β and IL-17, and Se supplementation successfully prevented this elevation. MIA caused an increase in foetal brain calcium, which was prevented by Se supplement. MIA caused in offspring a female-specific reduction in sociability, which was recovered by Se, and a male-specific reduction in social memory, which was not recovered by Se. Exposure to poly-I:C or selenium, but not both, reduced performance in the reinforcement learning task. Computational modelling indicated that this was predominantly due to increased exploratory behaviour, rather than reduced rate of learning the location of the food reward.This study demonstrates that while Se may be beneficial in ameliorating sociability deficits caused by MIA, it may have negative effects in other behavioural domains. Caution in the use of Se supplementation during pregnancy is therefore warranted.

Influence of environmental enrichment on sexual behavior and the process of learning and memory in a rat model of autism with valproic acid

Autism spectrum disorder (ASD) is a psychiatric disorder with severe behavioral consequences and no specific therapy. Its etiology is multifactorial, as it is caused by a complex interaction of genetic and environmental factors. In rats, prenatal exposure to the antiepileptic drug valproic acid (VPA) has been associated with an increased risk of autistic-like behaviors in offspring, including social behavior deficits, increased repetitive behaviors, and cognitive impairments. In addition, VPA-treated rats have shown altered sociosexual behaviors. However, the mechanisms underlying these alterations in reproductive processes in VPA-treated rats are not fully understood. Interestingly some abnormal behaviors in VPA autism models are improved by an enriched environment (EE). In the present study, we examined the effects of EE on memory performance and sexual behavior in male rats. We found that on postnatal day 90, EE reduced the time it took for both control and VPA-treated groups to find a hidden platform in the Morris water maze. On PND 100, prenatal exposure to VPA reduced total exploring time in object recognition tests. On PND 110, EE reduced mount and intromission latency and increased ejaculatory frequency in VPA-treated male rats. These results suggest that environmental stimuli significantly influence the onset of sexual behavior in VPA-treated male rats and that EE may be a potential tool for improving a variety of behavioral deficiencies in rodent models of autism.

Exposure of male adult zebrafish (Danio rerio) to triphenyl phosphate (TPhP) induces eye development disorders and disrupts neurotransmitter system-mediated abnormal locomotor behavior in larval offspring

Triphenyl phosphate (TPhP) is a widely used organophosphorus flame retardant, which has become ubiquitous in the environment. However, little information is available regarding its transgenerational effects. This study aimed to investigate the developmental toxicity of TPhP on F1 larvae offspring of adult male zebrafish exposed to various concentrations of TPhP for 28 or 60 days. The findings revealed significant morphological changes, alterations in locomotor behavior, variations in neurotransmitter, histopathological changes, oxidative stress levels, and disruption of Retinoic Acid (RA) signaling in the F1 larvae. After 28 and 60 days of TPhP exposure, the F1 larvae exhibited a myopia-like phenotype with pathological alterations in the lens and retina. The genes involved in the RA signaling pathway were down-regulated following parental TPhP exposure. Swimming speed and total distance of F1 larvae were significantly reduced by TPhP exposure, and long-term exposure to environmental levels of TPhP had more pronounced effects on locomotor behavior and neurotransmitter levels. In conclusion, TPhP induced histological and morphological alterations in the eyes of F1 larvae, leading to visual dysfunction, disruption of RA signaling and neurotransmitter systems, and ultimately resulting in neurobehavioral abnormalities. These findings highlight the importance of considering the impact of TPhP on the survival and population reproduction of wild larvae.

Maternal sevoflurane exposure increases the epilepsy susceptibility of adolescent offspring by interrupting interneuron development

BackgroundExposure to general anesthesia influences neuronal functions during brain development. Recently, interneurons were found to be involved in developmental neurotoxicity by anesthetic exposure. But the underlying mechanism and long-term consequences remain elusive.MethodsPregnant mice received 2.5% sevoflurane for 6-h on gestational day 14.5. Pentylenetetrazole (PTZ)-induced seizure, anxiety- and depression-like behavior tests were performed in 30- and 60-day-old male offspring. Cortical interneurons were labeled using Rosa26-EYFP/-; Nkx2.1-Cre mice. Immunofluorescence and electrophysiology were performed to determine the cortical interneuron properties. Q-PCR and in situ hybridization (ISH) were performed for the potential mechanism, and the finding was further validated by in utero electroporation (IUE).ResultsIn this study, we found that maternal sevoflurane exposure increased epilepsy susceptibility by using pentylenetetrazole (PTZ) induced-kindling models and enhanced anxiety- and depression-like behaviors in adolescent offspring. After sevoflurane exposure, the highly ordered cortical interneuron migration was disrupted in the fetal cortex. In addition, the resting membrane potentials of fast-spiking interneurons in the sevoflurane-treated group were more hyperpolarized in adolescence accompanied by an increase in inhibitory synapses. Both q-PCR and ISH indicated that CXCL12/CXCR4 signaling pathway downregulation might be a potential mechanism under sevoflurane developmental neurotoxicity which was further confirmed by IUE and behavioral tests. Although the above effects were obvious in adolescence, they did not persist into adulthood.ConclusionsOur findings demonstrate that maternal anesthesia impairs interneuron migration through the CXCL12/CXCR4 signaling pathway, and influences the interneuron properties, leading to the increased epilepsy susceptibility in adolescent offspring. Our study provides a novel perspective on the developmental neurotoxicity of the mechanistic link between maternal use of general anesthesia and increased susceptibility to epilepsy.

Maternal Obesity and ADHD: An Original Review of Evidence and Potential Mechanisms

This review explores the potential link between maternal obesity [body mass index (BMI) &gt;30 during pregnancy] and the development of attention-deficit/hyperactivity disorder (ADHD) in offspring. This study assesses the strength of this association by examining epidemiological studies and investigating possible biological mechanisms, including inflammation, oxidative stress, hormonal changes, prenatal programing, and epigenetic modifications. In addition, the review considers moderating variables and discusses the public health implications, with the objective of providing valuable insights into addressing this complex relationship for future clinical approaches and public health policies. This original review conducted a comprehensive literature search in August 2023 using various databases and keywords related to maternal obesity and ADHD. English articles published from 2005 to 2023, including case-control studies, cross-sectional studies, cohort studies, and reviews were considered. Multiple authors independently conducted searches, screened titles/abstracts, and extracted data to ensure rigorous methodology. Initially, 414 articles were retrieved from various databases and managed using Zotero. After eliminating 96 duplicates, 318 articles remained for screening on Rayyan. Of these, 47 papers met the eligibility criteria and underwent full-text review for inclusion in the study. Multiple studies suggest a positive correlation between maternal obesity and ADHD symptoms in children. Additionally, maternal obesity is associated with other neurodevelopmental disorders and behaviors in offspring, including heightened motor and anxiety behaviors. The complex relationship between maternal obesity and ADHD necessitates further investigation. Although existing research indicates associations, causality remains unconfirmed. Genome-wide association studies reveal shared genetic pathways, supported by rodent models. Human studies must address confounding factors. Promising interventions exist but require validation. Comprehensive research encompassing genetic, environmental, and metabolic factors is crucial for understanding the full impact of maternal obesity on neurodevelopmental outcomes.

Brain structural and functional signatures of multi-generational family history of suicidal behaviors in preadolescent children.

Parent-child transmission of suicidal behaviors has been extensively studied, but the investigation of a three-generation family suicide risk paradigm remains limited. In this study, we aimed to explore the behavioral and brain signatures of multi-generational family history of suicidal behaviors (FHoS) in preadolescents, utilizing a longitudinal design and the dataset from Adolescent Brain and Cognitive DevelopmentSM Study (ABCD Study®), which comprised 4 years of data and includes a total of 9,653 preadolescents. Our findings revealed that multi-generational FHoS was significantly associated with an increased risk of problematic behaviors and suicidal behaviors (suicide ideation and suicide attempt) in offspring. Interestingly, the problematic behaviors were further identified as a mediator in the multi-generational transmission of suicidal behaviors. Additionally, we observed alterations in brain structure within superior temporal gyrus (STG), precentral/postcentral cortex, posterior parietal cortex (PPC), cingulate cortex (CC), and planum temporale (PT), as well as disrupted functional connectivity of default mode network (DMN), ventral attention network (VAN), dorsal attention network (DAN), fronto-parietal network (FPN), and cingulo-opercular network (CON) among preadolescents with FHoS. These results provide compelling longitudinal evidence at the population level, highlighting the associations between multi-generational FHoS and maladaptive behavioral and neurodevelopmental outcomes in offspring. These findings underscore the need for early preventive measures aimed at mitigating the familial transmission of suicide risk and reducing the global burden of deaths among children and adolescents.

Maternal exposure to bisphenol S reduces anxiety and impairs collective antipredator behavior of male zebrafish (Danio rerio) offspring through dysregulation of their serotonergic system

Bisphenol S (BPS) is a common endocrine-disrupting chemical globally used in several consumer and industrial products. Although previous studies suggested that BPS induces multiple effects in exposed organisms, very little is known about its intergenerational effect on offspring behavior and/or the potential underlying mechanisms. To this end, adult female zebrafish Danio rerio were exposed to BPS (0, 10, 30 µg/L) and 1 µg/L of 17-β-estradiol (E2) as a positive control for 60 days. Afterwards, female fish were bred with untreated males, and their offspring were raised to 6 months old in control water. Maternal exposure to BPS decreased male offspring anxiety and antipredator behaviors while boldness remained unaffected. Specifically, maternal exposure to 10 and 30 µg/L BPS and 1 µg/L E2 were found to impact male offspring anxiety levels as they decreased the total time that individuals spent in the dark zone in the light/dark box test and increased the total track length in the center of the open field test. In addition, maternal exposure to all concentrations of BPS and E2 disrupted antipredator responses of male offspring by decreasing shoal cohesion in the presence of chemical alarm cues derived from conspecifics, which communicated high risk. To elucidate the possible molecular mechanism underlying these neuro-behavioral effects of BPS, we assessed the serotonergic system via changes in mRNA expression of serotonin receptors, including the 5-HT1A, 5-HT1B, and 5-HT1D subtypes, the serotonin transporter and monoamine oxidase (MAO). The impaired anxiety and antipredator responses were associated with reduced levels of 5-HT1A subtype and MAO mRNA expression within the brain of adult male offspring. Collectively, the results of this study demonstrate that maternal exposure to environmental concentrations of BPS can interfere with the serotonergic signaling pathway in the developing brain, subsequently leading to the onset of a suite of behavioral deficits in adult offspring.

Prenatal caffeine exposure induces autism-like behaviors in offspring under a high-fat diet via the gut microbiota-IL-17A-brain axis

Prenatal caffeine exposure (PCE) is a significant contributor to intrauterine growth retardation (IUGR) in offspring, which has been linked to an increased susceptibility to autism spectrum disorder (ASD) later in life. Additionally, a high-fat diet (HFD) has been shown to exacerbate ASD-like behaviors, but the underlying mechanisms remain unclear. In this study, we first noted in the rat model of IUGR induced by PCE that male PCE offspring exhibited typical ASD-like behaviors post-birth, in contrast to their female counterparts. The female PCE offspring demonstrated only reduced abilities in free exploration and spatial memory. Importantly, both male and female PCE offspring displayed ASD-like behaviors when exposed to HFD. We further observed that PCE + HFD offspring exhibited damaged intestinal mucus barriers and disturbed gut microbiota, resulting in an increased abundance of Escherichia coli (E. coli). The induced differentiation of colonic Th17 cells by E. coli led to an increased secretion of IL-17A, which entered the hippocampus through peripheral circulation and caused synaptic damage in hippocampal neurons, ultimately resulting in ASD development. Our strain transplantation experiment suggested that E. coli-mediated increase of IL-17A may be the core mechanism of ASD with a fetal origin. In conclusion, PCE and HFD are potential risk factors for ASD, and E. coli-mediated IL-17A may play a crucial role in fetal-originated ASD through the gut-brain axis.

The influence of maternal diet on offspring's gut microbiota in early life.

The influence of maternal diet on offspring's health is an area of study that is linked to epigenetics. Maternal diet contributes to determining the health status of offspring and maternally linked mechanisms and is a global health challenge that requires attention. The impact of gut microbiota on host metabolism and offspring health is still not established. In this review, we intend to discuss the evidence on the impact of maternal diet and the health of offspring gut microbiota. The paper focuses on the gut microbiome of animal models. It captures the maternal diet and its influence on the offspring's gut microbiota, behavior that is supported by cell experimental results. Both inflammation and immune status of offspring induced by maternal diet are discussed. Finally, this review used predicted biological pathways involved inmaternal diet and offspring health, and the influence of maternal diet on gut microbiota and offspring behavior. Obesity, diabetes, asthma and allergies, and neurodegenerative disorders and prospects for maternal diet, and microbiota and offspring health were discussed. The review was able to gather that a high-fat diet during pregnancy created a long-lasting metabolic signature on the infant's innate immune system, altering inflammation in the offspring microbiota, which predisposed offspring to obesity and metabolic diseases in adulthood.

Early life social complexity shapes adult neural processing in the communal spiny mouse Acomys cahirinus.

Early life social rearing has profound consequences on offspring behavior and resilience. Yet, most studies examining early life development in rodents use species whose young are born immobile and do not produce complex social behavior until later in development. Furthermore, models of rearing under increased social complexity, rather than deprivation, are needed to provide alternative insight into the development of social neural circuitry. To understand precocial offspring social development, we manipulated early life social complexity in the communal spiny mouse Acomys cahirinus and assessed long-term consequences on offspring social behavior, exploration, and neural responses to novel social stimuli. Spiny mouse pups were raised in the presence or absence of a non-kin breeding group. Upon adulthood, subjects underwent social interaction tests, an open field test, and a novel object test. Subjects were then exposed to a novel conspecific and novel group and neural responses were quantified via immunohistochemical staining in brain regions associated with social behavior. Early life social experience did not influence behavior in the test battery, but it did influence social processing. In animals exposed to non-kin during development, adult lateral septal neural responses toward a novel conspecific were weaker and hypothalamic neural responses toward a mixed-sex group were stronger. Communal species may exhibit robust behavioral resilience to the early life social environment. But the early life environment can affect how novel social information is processed in the brain during adulthood, with long-term consequences that are likely to shape their behavioral trajectory.

Effects of parental exposure to amitriptyline on the survival, development, behavior, and gene expression in zebrafish offspring

In mammals, parental exposure to amitriptyline (AMI) has been proven to contribute to congenital disabilities in their offspring. However, no studies have paid attention to the adverse effects of parental exposure to amitriptyline on fish offspring. In this study, we exposed adult zebrafish (F0) to AMI (0.8 μg/L) for 21 days. Subsequently, these zebrafish (F0) were allowed to mate, and their offspring (F1) were collected to culture in clean water for 5 days. The mortality rate, average hatching time, and heart rate at 48 h post-fertilization (hpf) of F1 were investigated. Our results showed that parental exposure to AMI induced tachycardia and increased mortality in F1 zebrafish. Under a light/dark transition test, F1 larvae born from AMI-exposed parents exhibited lower locomotor activity in the dark period and decreased thigmotaxis in the light period. The transcriptome analysis showed that parental AMI exposure dysregulated some key pathways in their offspring. Through the prediction of key driver analysis, six differentially expressed genes (DEGs) were revealed as key driver genes involved in protein processing in endoplasmic reticulum (hspa5, hsp70.1, hsp90a), ribosome (rps27a) and PPAR signaling pathway (pparab and fabp2). Considering that the concentration of AMI residual components in natural water bodies may be over our test concentration (0.8 μg/L), our findings suggested that toxicity of parental exposure to the offspring of fish should receive greater attention.

Effects of pre-gestational exposure to the stressors and perinatal bupropion administration on the firing activity of serotonergic neurons and anxiety-like behavior in rats

Exposure by women to stressors before pregnancy increases their risk of contracting prenatal depression, a condition which typically may require antidepressant treatment. And even though such perinatal antidepressant treatment is generally considered to be safe. For the mother, its effects on the development and functioning of the offspring`s brain remain unknown. In this study, we aimed to investigate the effects of pregestational chronic unpredictable stress (CUS) and perinatal bupropion on the anxiety behavior and firing activity of the dorsal raphe nucleus (DRN) serotonin (5-HT) neurons. Female rats underwent CUS for three weeks before mating. Bupropion was administered to them from gestation day ten until their offspring were weaned. Behavioral (elevated plus maze or EPM test) and neurophysiological (single-unit in vivo electrophysiology) assessments were performed on offspring who reached the age of 48–56 days. We found that maternal CUS and perinatal bupropion, as separate factors on their own, did not change offspring behavior. There was, however, an interaction between their effects on the number of entries to the open arms and time spent in the intersection: maternal CUS tended to decrease these values, and perinatal bupropion tended to diminish CUS effect. Maternal CUS increased the firing activity of 5-HT neurons in males, but not females. Perinatal bupropion did not alter the firing activity of 5-HT neurons but tended to potentiate the maternal CUS-induced increase in 5-HT neuronal firing activity. The CUS-induced increase in firing activity of 5-HT neurons might be a compensatory mechanism that diminishes the negative effects of maternal stress. Perinatal bupropion does not alter the offspring`s anxiety and firing activity of 5-HT, but it does intervene in the effects of maternal stress.