SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral acetylcholine production
Summary: 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 th...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-06-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223010313 |
| _version_ | 1797811095906287616 |
|---|---|
| author | Naomi Oka Kazuya Shimada Azusa Ishii Nobuyuki Kobayashi Kazuhiro Kondo |
| author_facet | Naomi Oka Kazuya Shimada Azusa Ishii Nobuyuki Kobayashi Kazuhiro Kondo |
| author_sort | Naomi Oka |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-13T07:17:36Z |
| format | Article |
| id | doaj.art-ede515809d0a496585ac1d4bb8958245 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-13T07:17:36Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-ede515809d0a496585ac1d4bb89582452023-06-05T04:13:05ZengElsevieriScience2589-00422023-06-01266106954SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral acetylcholine productionNaomi Oka0Kazuya Shimada1Azusa Ishii2Nobuyuki Kobayashi3Kazuhiro Kondo4Department of Virology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, JapanDepartment of Virology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, JapanDepartment of Virology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, JapanDepartment of Virology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, JapanDepartment of Virology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004223010313NeuroscienceBehavioral neuroscienceVirology |
| spellingShingle | Naomi Oka Kazuya Shimada Azusa Ishii Nobuyuki Kobayashi Kazuhiro Kondo SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral acetylcholine production iScience Neuroscience Behavioral neuroscience Virology |
| title | SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral acetylcholine production |
| title_full | SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral acetylcholine production |
| title_fullStr | SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral acetylcholine production |
| title_full_unstemmed | SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral acetylcholine production |
| title_short | SARS-CoV-2 S1 protein causes brain inflammation by reducing intracerebral acetylcholine production |
| title_sort | sars cov 2 s1 protein causes brain inflammation by reducing intracerebral acetylcholine production |
| topic | Neuroscience Behavioral neuroscience Virology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223010313 |
| work_keys_str_mv | AT naomioka sarscov2s1proteincausesbraininflammationbyreducingintracerebralacetylcholineproduction AT kazuyashimada sarscov2s1proteincausesbraininflammationbyreducingintracerebralacetylcholineproduction AT azusaishii sarscov2s1proteincausesbraininflammationbyreducingintracerebralacetylcholineproduction AT nobuyukikobayashi sarscov2s1proteincausesbraininflammationbyreducingintracerebralacetylcholineproduction AT kazuhirokondo sarscov2s1proteincausesbraininflammationbyreducingintracerebralacetylcholineproduction |