Exposure to Early Life Stress Results in Epigenetic Changes in Neurotrophic Factor Gene Expression in a Parkinsonian Rat Model

Early life adversity increases the risk of mental disorders later in life. Chronic early life stress may alter neurotrophic factor gene expression including those for brain derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF) that are important in neuronal growth, survival, and maintenance. Maternal separation was used in this study to model early life stress. Following unilateral injection of a mild dose of 6-hydroxydopamine (6-OHDA), we measured corticosterone (CORT) in the blood and striatum of stressed and nonstressed rats; we also measured DNA methylation and BDNF and GDNF gene expression in the striatum using real time PCR. In the presence of stress, we found that there was increased corticosterone concentration in both blood and striatal tissue. Further to this, we found higher DNA methylation and decreased neurotrophic factor gene expression. 6-OHDA lesion increased neurotrophic factor gene expression in both stressed and nonstressed rats but this increase was higher in the nonstressed rats. Our results suggest that exposure to early postnatal stress increases corticosterone concentration which leads to increased DNA methylation. This effect results in decreased BDNF and GDNF gene expression in the striatum leading to decreased protection against subsequent insults later in life

Mycobacterium tuberculosis-Induced Maternal Immune Activation Promotes Autism-Like Phenotype in Infected Mice Offspring

The maternal system’s exposure to pathogens during pregnancy influences fetal brain development causing a persistent inflammation characterized by elevated pro-inflammatory cytokine levels in offspring. Mycobacterium tuberculosis (Mtb) is a global pathogen that causes tuberculosis, a pandemic responsible for health and economic burdens. Although it is known that maternal infections increase the risk of autism spectrum disorder (ASD), it is not known whether Mtb infection is sufficient to induce ASD associated behaviors, immune dysregulation and altered expression of synaptic regulatory genes. The current study infected pregnant Balb/c mice with Mtb H37Rv and valproic acid (VPA) individually and in combination. Plasma cytokine profiles were measured in offspring using the Bio-plex Th17 pro mouse cytokine panel. Mtb infection increased plasma interleukin (IL)-6 and IL-17A, while tumor necrosis factor alpha (TNF-α), interferon (IFN)-γ and IL-1β were reduced when compared with saline. Mtb-induced maternal immune activation (MIA) offspring displayed increased grooming behavior. The study also revealed dysregulation in gene expression of synaptic molecules in the cerebellum. MIA rescued the VPA-induced effects on self-grooming and social interaction behaviors. Our finding therefore highlights a potential role of Mtb as a MIA agent that can potentially contribute to ASD

Early Life Stress and Brain Plasticity: From Alterations of Brain Morphology to Development of Psychopathology

Advances in our understanding of the genetics of mental disorders (MD) have contributed to a better understanding of their pathophysiology. Nonetheless, several questions and doubts remain. Recent research has focused on the role of the environment in developing mental disorders, and the advent of neuroscientific methodologies has opened up new avenues of inquiry. However, the mechanism by which childhood stress affects neurodevelopment via mechanisms, such as gene-environment interactions and epigenetic regulation leading to diseases in adulthood, is unclear. This paper aims to review the evidence on the role of early life stress and parental psychopathology in the pathophysiology and clinical expression of MD. Methodology: The study will conduct a comprehensive systematic review using medical search terms (MeSH). Electronic searches for published studies will be performed using the MEDLINE (PubMed), EMBASE, Scopus, PsychINFO, Web of Science, and Google Scholar databases. We will look for research on the neuroplasticity effects of early life stress on development and review articles that evaluate cognitive functions and the development of psychopathology and MD. Before identifying full-text articles, several studies will be filtered based on titles, abstracts, keywords, and synonyms. Publications to be included in the review will be assessed for quality and consistency before inclusion. Data will be extracted independently and duplicated by two authors from each eligible study to ensure consistency between reviews. All databases will be searched from inception until July 2021 and will be limited to human studies. The search will be limited only to publication in the English language and any publication that can be converted to English. Discussion and Conclusions: The findings of this review will meticulously articulate the effects of childhood adversity, such as ELS and parental psychopathology on cognitive development and neuroplasticity

Effectiveness of Double-Hit Model (Post-Weaning Social Isolation and NMDA Receptor Antagonist) in the Development of Schizophrenic like Symptoms on Rodents: A Protocol for a Systematic Review

Background: Schizophrenia is a heterogeneous neuropsychiatric disorder, categorized by positive, negative, and cognitive symptoms. In trying to improve the diagnosis and treatment of schizophrenia, researchers have turned to “dual hit” models of schizophrenia that are able to reproduce all symptoms of the disorder. The main objective of this protocol is to present a transparent process on how we plan to review the existing international literature on the effectiveness of “dual hit” models used to induce schizophrenia on rodents. Methods: Literature search strategies will be developed using medical search headings (MeSH). The MEDLINE (PubMed), EMBASE, and Google Scholar databases will be used to search for electronically published studies. We will search for studies involving inducing schizophrenic symptoms using “dual hit” rodent models (post-weaning social isolation and NMDA receptor antagonist). Studies will be screened by titles, abstracts, keywords, and synonyms followed by identifying the full-text articles. All studies that will pass quality assessment will be included. Data will be extracted by two authors independently and in duplicate from each eligible study to ensure that there is consistency between reviews. If the design and comparator are sufficiently homogenous for all studies, a meta-analysis will be conducted using a random-effect model. Discussion: The results of this review will contribute to the development of new “dual hit” models that will be able to characterize schizophrenia symptoms better. It will also shed light to researchers on new developments that need to be made in improving animal models of schizophrenia

Early Life Stress and Brain Plasticity: From Alterations of Brain Morphology to Development of Psychopathology

Advances in our understanding of the genetics of mental disorders (MD) have contributed to a better understanding of their pathophysiology. Nonetheless, several questions and doubts remain. Recent research has focused on the role of the environment in developing mental disorders, and the advent of neuroscientific methodologies has opened up new avenues of inquiry. However, the mechanism by which childhood stress affects neurodevelopment via mechanisms, such as gene-environment interactions and epigenetic regulation leading to diseases in adulthood, is unclear. This paper aims to review the evidence on the role of early life stress and parental psychopathology in the pathophysiology and clinical expression of MD. Methodology: The study will conduct a comprehensive systematic review using medical search terms (MeSH). Electronic searches for published studies will be performed using the MEDLINE (PubMed), EMBASE, Scopus, PsychINFO, Web of Science, and Google Scholar databases. We will look for research on the neuroplasticity effects of early life stress on development and review articles that evaluate cognitive functions and the development of psychopathology and MD. Before identifying full-text articles, several studies will be filtered based on titles, abstracts, keywords, and synonyms. Publications to be included in the review will be assessed for quality and consistency before inclusion. Data will be extracted independently and duplicated by two authors from each eligible study to ensure consistency between reviews. All databases will be searched from inception until July 2021 and will be limited to human studies. The search will be limited only to publication in the English language and any publication that can be converted to English. Discussion and Conclusions: The findings of this review will meticulously articulate the effects of childhood adversity, such as ELS and parental psychopathology on cognitive development and neuroplasticity