SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral acetylcholine production

Naomi Oka; Kazuya Shimada; Azusa Ishii; Nobuyuki Kobayashi; Kazuhiro Kondo

doi:10.1016/j.isci.2023.106954

SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral acetylcholine production

iScience. 2023 Jun 16;26(6):106954. doi: 10.1016/j.isci.2023.106954. Epub 2023 May 24.

Authors

Naomi Oka¹, Kazuya Shimada¹, Azusa Ishii¹, Nobuyuki Kobayashi¹, Kazuhiro Kondo¹

Affiliation

¹ Department of Virology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan.

Abstract

Neurological complications that occur in SARS-CoV-2 infection, such as olfactory dysfunction, brain inflammation, malaise, and depressive symptoms, are thought to contribute to long COVID. However, in autopsies of patients who have died from COVID-19, there is normally no direct evidence that central nervous system damage is due to proliferation of SARS-CoV-2. For this reason, many aspects of the pathogenesis mechanisms of such symptoms remain unknown. Expressing SARS-CoV-2 S1 protein in the nasal cavity of mice was associated with increased apoptosis of the olfactory system and decreased intracerebral acetylcholine production. The decrease in acetylcholine production was associated with brain inflammation, malaise, depressive clinical signs, and decreased expression of the cytokine degrading factor ZFP36. Administering the cholinesterase inhibitor donepezil to the mice improved brain inflammation, malaise and depressive clinical signs. These findings could contribute to the elucidation of the pathogenesis mechanisms of neurological complications associated with COVID-19 and long COVID.

Keywords: Behavioral neuroscience; Neuroscience; Virology.