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A Sleeping Opportunity Does Not Restore Hippocampal Alterations Induced by 10 Days of Sleep Restriction in Rats

Year: 2025

Type: article

Abstract: Sleep loss has been implicated in age-related cognitive decline. Experimental sleep restriction (SR) alters the physiology of multiple brain regions and increases blood-brain barrier (BBB) permeability. Among these regions, the hippocampus of both humans and rodents shows alterations that endure longer than in other areas such as the basal ganglia and hypothalamus. In the present study, adult male rats were subjected to 10 days of SR using the modified multiple platform method (MMPM). Immediately after restriction, SR animals exhibited increased IBA-1 immunoreactivity (IR) and cell number, consistent with microglial activation; these morphological changes persisted after a 4 h recovery period. Synaptophysin (Syn) expression was significantly reduced after SR and remained decreased following rest, while the pERK/ERK ratio was significantly increased by the end of the recovery window. These molecular alterations were accompanied by disrupted hippocampal local field potentials (LFPs), characterized by increased alpha and beta activity and reduced delta and theta power. Importantly, SR rats showed impaired short-term memory in the novel object and object location recognition tests after the recovery period. Together, these findings demonstrate that subchronic SR induces persistent microglial and synaptic alterations and abnormal ERK signaling that remain after short rest, correlating with hippocampal network dysfunction and memory impairment.

Source: Neurochemical Research

DOI: 10.1007/s11064-025-04561-1