Publication
miRNA-132/212 Deficiency Disrupts Selective Corticosterone Modulation of Dorsal vs. Ventral Hippocampal Metaplasticity
Publisher:
MDPI AG
Date:
31-05-2023
DOI:
10.3390/IJMS24119565
Abstract: Cortisol is a potent human steroid hormone that plays key roles in the central nervous system, influencing processes such as brain neuronal synaptic plasticity and regulating the expression of emotional and behavioral responses. The relevance of cortisol stands out in the disease, as its dysregulation is associated with debilitating conditions such as Alzheimer’s Disease, chronic stress, anxiety and depression. Among other brain regions, cortisol importantly influences the function of the hippoc us, a structure central for memory and emotional information processing. The mechanisms fine-tuning the different synaptic responses of the hippoc us to steroid hormone signaling remain, however, poorly understood. Using ex vivo electrophysiology and wild type (WT) and miR-132/miR-212 microRNAs knockout (miRNA-132/212−/−) mice, we examined the effects of corticosterone (the rodent’s equivalent to cortisol in humans) on the synaptic properties of the dorsal and ventral hippoc us. In WT mice, corticosterone predominantly inhibited metaplasticity in the dorsal WT hippoc i, whereas it significantly dysregulated both synaptic transmission and metaplasticity at dorsal and ventral regions of miR–132/212−/− hippoc i. Western blotting further revealed significantly augmented levels of endogenous CREB and a significant CREB reduction in response to corticosterone only in miR–132/212−/− hippoc i. Sirt1 levels were also endogenously enhanced in the miR–132/212−/− hippoc i but unaltered by corticosterone, whereas the levels of phospo-MSK1 were only reduced by corticosterone in WT, not in miR–132/212−/− hippoc i. In behavioral studies using the elevated plus maze, miRNA-132/212−/− mice further showed reduced anxiety-like behavior. These observations propose miRNA-132/212 as potential region-selective regulators of the effects of steroid hormones on hippoc al functions, thus likely fine-tuning hippoc us-dependent memory and emotional processing.