Stress-induced anxiety and myelin plasticity : insights from in vivo and in vitro studies
Year: 2024
Type: dissertation
Abstract: Anxiety disorders are the leading psychiatric conditions in Europe, and greatly impact quality of life. They stem from both genetic and environmental factors like psychosocial stress. Current psychotherapy and anxiolytic treatments show limited efficacy and high relapse rates. Identifying the molecular and cellular mechanisms of anxiety disorders is vital for developing better treatments. Our first aim was to examine the brain gene expression patterns of innate anxiety and anxiety induced by psychosocial stress. The gene expression profiles of mouse strains with low or high levels of innate anxiety-like behavior and those of mice subjected to chronic social defeat stress (CSDS) were similar in the hippocampus (HPC) but not in the frontal cortex. However, these patterns converged on inflammation-related pathways. Putative anxiolytic drug candidates were also identified, including captopril and medrysone, predicted to induce gene expression changes contrary to those seen in innate or stress-induced anxiety-like behavior. Regarding the second aim, our group has identified brain region and strain-specific differences in myelin thickness in response to CSDS in mice. How CSDS affects another form of myelin plasticity, the nodes of Ranvier morphology, was studied here. Immunohistochemistry demonstrated shorter paranodes in the medial prefrontal cortex (mPFC) of stress resilient C57BL/6NCrl (B6) mice and longer nodes in susceptible DBA/2NCrl (D2) mice compared to their controls. Repeated DREADD-mediated activation of ventral HPC neurons projecting to mPFC decreased anxiety-like behavior and paranode length along stimulated axons. Lastly, strain differences in oligodendrocytes (OLs) response to glucocorticoids was investigated as a potential regulator for stress-induced myelin plasticity. In vitro cultures of OPCs isolated from B6 and D2 mice characterized by immunohistochemistry showed that acute corticosterone (CORT) treatment affected OPC proliferation, OL maturation, and myelin production in a strain-specific manner. Prolonged exposure to the glucocorticoid dexamethasone (DEX) inhibited OPC proliferation, OL maturation, and myelin production in cultures from the two strains. In summary, OL response to glucocorticoids depended on their genetic background, and it may contribute to stress-induced myelin plasticity. Together, these findings highlight new insights into mechanisms underlying stress-induced myelin plasticity, informing potential novel treatment strategies for anxiety disorders.
Source: Työväentutkimus Vuosikirja
Author: Gigliotta, Adrien
Language: English
Subfield: Behavioral Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7198670088