The role of TRPV4 in acute sleep deprivation-induced memory impairment: Mechanisms of calcium dysregulation and synaptic plasticity disruption

Abstract

Acute sleep deprivation (ASD) impairs memory formation, but the underlying mechanisms remain unclear. In this study, we employed an ASD model combined with fear conditioning to investigate these mechanisms. mRNA sequencing revealed upregulated expression of Transient Receptor Potential Vanilloid 4 (TRPV4), a nonselective Ca²⁺-permeable cation channel critical for calcium signaling, in mice with ASD-induced memory impairments. Notably, TRPV4 knockdown reversed ASD-induced memory deficits. ASD was associated with increased intracellular Ca²⁺ concentrations, reduced spine density, and decreased expression of postsynaptic density protein 95 (PSD95), a key regulator of synaptic plasticity. These findings suggest that ASD may cause Ca²⁺ overload, leading to disrupted synaptic plasticity and impaired learning and memory. Importantly, TRPV4 knockdown significantly reduced Ca²⁺ concentrations, mitigated synaptic plasticity impairments, and contributed to memory restoration. Together, these findings demonstrate a protective role of TRPV4 knockdown against ASD-induced memory deficits and highlight TRPV4 as a potential therapeutic target for memory impairment associated with ASD.