Investigating the Neurobiological Effects of Early Life Adversity on Social Behavior and Hippocampal Plasticity

Abstract

Early life adversity (ELA), which includes interpersonal conflict or environmental trauma, puts individuals at a higher susceptibility to neuropsychiatric illnesses such as anxiety and depression. These circumstances have corresponding neurobiological alterations in various brain regions, such as the hippocampus, that persist until adulthood. This study utilizes two rodent models which have been extensively studied in the ELA field to understand the underlying mechanisms of effects stemming from ELA: the maternal separation and early weaning (MSEW) model and limited bedding and nesting (LBN) model. Both models have provided findings which suggest an increase in anxiety-like and depression-like behavior with associated decreases in hippocampal adult plasticity. The present study seeks to assess social behavior deficits after ELA. Therefore, this study uses C57BL/6J mice to learn more about hippocampal changes that result from the MSEW and LBN paradigms that model specific kinds of ELA. This study explores rodent dentate gyrus and CA2 hippocampal regions which have displayed an important role in functioning social memory. In this study, ELA effects on neural plasticity were investigated. This entailed examining adult neurogenesis, measured through immature neuron cell count and perineuronal nets. However, underlying changes were different among MSEW and LBN mice. MSEW mice displayed significant decreases in immature granule cell counts, with corresponding progenitor cell reductions. However, LBN mice had no significant differences in immature granule cell counts, and instead had a significant increase in PNN intensity, which was not observed in MSEW mice. Furthermore, this study administered environmental enrichment (EE) and chABC in hopes of rescuing the social memory deficits found for MSEW and LBN mice, respectively. This study found social memory rescued for MSEW mice that went through EE, and LBN mice that were administered chABC. MSEW EE mice had neural changes further investigated, which presented a significant increase in immature granule cells compared to MSEW mice that did not go through EE. Additionally, senescent cells (SNCs) were explored as their inverse relationship with neural plasticity has been shown. It was found that EE MSEW mice had a significant decrease in SNCs when compared to MSEW mice that did not receive EE. Understanding the underlying mechanisms to behavioral and neurobiological alterations stemming from MSEW and LBN paradigms, will aid in making effective treatments for neuropsychiatric illnesses that stem from ELA.