Role of Neurosteroids on Hippocampal-dependent Memory: A Mini Review

Neurosteroids are steroidal hormones synthesized within the central or peripheral nervous tissues, either de novo from cholesterol or steroid hormone precursors, and that accumulate in the nervous system and have the ability to modulate neuronal excitability by rapid non-genomic effects on membrane receptors (including those of neurotransmitters) and conventional genomic actions involving both regulation of target gene expression. In the hippocampus, neurosteroids may be the primary mediators of steroid-induced synaptic plasticity. Studies indicate that the depletion of neurosteroids can create learning and memory disorders. The findings are derived from an online literature search across reputable databases, including Google Scholar, PubMed, and Scopus. A literature survey indicates that the neuro-modulatory role of neurosteroids in regulating anxiety, memory, cognition, and age-dependent changes in the nervous system requires further investigation. Although the rapid modulatory action of sex steroids on synapses has been studied in hippocampal neurons for several decades, the essential molecular mechanisms underlying neurosteroid action, as an endogenous source of steroids, remain poorly understood. Our previous study indicated that neural repair can be facilitated through androgens. Additionally, testosterone depletion alters androgen receptor expression in the hippocampus, leading to downregulation of dendritic spine-related proteins and learning disorders. The prospects and potential of neurosteroids as therapeutic agents or targets in neurogenerative disorders and aging remain largely underdeveloped, and more work is needed to fully elucidate their roles in maintaining healthy hippocampal synaptic plasticity.