0202 Sleep Deprivation: Cognitive Decline and Hippocampal Neuroinflammation

Abstract

Abstract Introduction A highly conserved biological process, sleep is imperative for healthy brain function. Sleep deprivation (SD) disrupts cognition and increases susceptibility to neurological disorders. The first step to developing mitigation strategies, this study investigated mechanisms underlying sleep-induced cognitive impairment, including hippocampal neuroinflammation. Methods All animal activities were approved under an IACUC protocol. Male Sprague-Dawley rats (N = 50) underwent 120 h of SD. Novel Object Recognition (NOR) and Passive-Avoidance Task (PAT) assessed cognitive performance (n = 6-12), followed by humane euthanization. Protein analysis of hippocampal tissue was performed using immunohistochemistry (IHC, n = 3-6) and enzyme-linked immunoassay (ELISA, n = 8-13). Microglia (Iba-1 marker) and astrocyte (GFAP marker) populations were quantified using IHC and ImageJ. The ELISA V-PLEX assay was used to assess concentration of pro-/anti-inflammatory mediators. Results Tested 24 h after training, SD rats had significantly lower cognitive performance in NOR (p< 0.05) and PAT (p< 0.01). Percentage of Iba-1+ microglia in the stratum radiatum of CA1 (p< 0.05) and CA2 (p< 0.05) hippocampal subregions was higher among SD rats. This SD-induced increase in microglia was not found in the pyramidal layer of CA1/2/3 (p>0.05). There was no SD-associated change in percentage of GFAP+ astrocytes in any hippocampal subregion (p>0.05). ELISA analysis found SD rats had higher levels of pro-inflammatory chemokine ligand 1 (CXCL1, p< 0.05) and anti-inflammatory interleukin-10 (IL-10, p=0.07) in the hippocampus. Conclusion SD-induced cognitive impairment was associated with increased microglia presence in CA1/2 subregions of the hippocampus. Increased expression of hippocampal CXCL1 after SD indicates these CA1/2 microglia are pro-inflammatory, leading to neuroinflammation in regions that mediate declarative memory. Although IL-10 trended to increase after SD, this neuroprotective anti-inflammatory factor did not prevent SD-induced performance decline or microglia recruitment. Based on these findings, it is suggested that blocking pro-inflammatory microglia pathways in the CA1/2 may prevent SD-induced cognitive dysfunction. Support (if any) AFOSR grant 20RHCOR04