Immunization with 674-685 fragment of SARS-Cov-2 spike protein induces neuroinflammation and impairs episodic memory of mice

Abstract

COVID-19 is accompanied by strong inflammatory reaction and is often followed by long-term cognitive disorders. The fragment 674-685 of SARS-Cov-2 spike protein was shown to interact with α7 nicotinic acetylcholine receptor involved in regulating both inflammatory reactions and cognitive functions. Here we show that mice immunized with the peptide corresponding to 674-685 fragment of SARS-Cov-2 spike protein conjugated to hemocyanin (KLH-674-685) demonstrate decreased level of α7 nicotinic acetylcholine receptors, increased levels of IL-1β and TNFα in the brain and impairment of episodic memory. Choline injections prevented α7 nicotinic receptor decline and memory loss. Mice injected with immunoglobulins obtained from the blood of (KLH-674-685)-immunized mice also demonstrated episodic memory decline. These data allow suggesting that post-COVID memory impairment in humans is related to SARS-Cov-2 spike protein-specific immune reaction. The mechanisms of such effect are being discussed.

Keywords: Antibodies; COVID-19; Episodic memory; Neuroinflammation; SARS-CoV-2 spike protein; α7 nicotinic acetylcholine receptor.