The Effect of the SARS-CoV-2 Spike Protein on Demyelination and Neuroinflammation Associated with Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease of the central nervous system (CNS) with an unknown etiology. Evidence suggests that viral infections, such as the one caused by SARS-CoV-2, the etiological agent of COVID-19, have been frequently associated with neurological manifestations, incl demyelinating processes. In this context, the Spike protein (SPK) stands out not only for mediating viral entry but also for inducing inflammatory responses. Therefore, this study investigated the effects of intracerebroventricular (i.c.v.) infusion of SPK on the induction or potentiation of demyelination and neuroinflammation. To this end, an i.c.v. SPK infusion model (6.5 μg) was utilized alongside a cuprizone (CPZ)-induced demyelination model. Eight-week-old animals received an i.c.v. infusion of either PBS or SPK. At 12 weeks of age, they were fed for two weeks with either standard chow or chow mixed with 0.2% CPZ, establishing the following experimental groups: PBS, SPK, PBS+CPZ, and SPK+CPZ. Demyelination was assessed via Western blotting immunofluorescence, and transmission electron microscopy, while inflammator mediators were analyzed by PCR. Cognitive and sensory alterations were investigated through behavioral tests. The SPK group exhibited impairment in novel ob recognition and reduced tactile sensitivity in the von Frey test compared to the othergroups. Additionally, a reduction in CNPase expression and an increase in GFAP were observed in the SPK group, suggesting demyelination associated with astrocy activation relative to the remaining groups. In conclusion, SPK may neuroinflammatory and demyelinating alterations, suggesting its potential role as an aggravating factor in diseases such as multiple sclerosis.