CCR3 knockdown attenuates prolonged underwater operations-induced cognitive impairment via alleviating microglia-mediated neuroinflammation

Maintaining cognitive integrity is crucial during underwater operations, which can significantly impact work performance and risk severe accidents. However, the cognitive effects of underwater operations and their underlying mechanism remain elusive, posing great challenges to the medical protection of professionals concerned. Here, we found that a single underwater operation session affects cognition in a time-dependent model. Prolonged exposure elicits significant cognitive impairment and hippocampal dysfunction, accompanied by increased neuroinflammation. Furthermore, RNA sequencing (RNA-seq) analysis revealed the involvement of neuroinflammation and highlighted the critical role of CCR3. Knockdown of CCR3 significantly rescued cognitive impairment and hippocampal dysfunction and reversed the upregulation of pro-inflammatory cytokines, by switching the activated microglia from a pro-inflammatory to a neuroprotective phenotype. Taken together, these results highlighted the time-dependent effects of a single underwater operation session on cognitive function. Knocking down CCR3 can attenuate neuroinflammation by regulating polarization of activated microglia, thereby alleviating prolonged underwater operations-induced cognitive impairment. [Display omitted] •A single prolonged underwater operation induces cognitive impairment•CCR3 is crucial in prolonged underwater operation-induced neuroinflammation•CCR3 knockdown regulates polarization of activated microglia•CCR3 provides a target for the protection of cognition in special environments Biological sciences; Neuroscience; Systems neuroscience; Sensory neuroscience