ArticleFrontiers in cellular neuroscience2021
Expression of the ACE2 Virus Entry Protein in the Nervus Terminalis Reveals the Potential for an Alternative Route to Brain Infection in COVID-19.
Article in Frontiers in cellular neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Brain microstructural alterations in COVID-19: a systematic review of diffusion weighted imaging studies.Brain imaging and behavior · 2026Pooled it
- Review
- Golgi Fragmentation as a Potential Link Between SARS-CoV-2 Infection and Alzheimer's Disease: Mechanisms and Implications for Neurodegeneration in Long COVID.Sub-cellular biochemistry · 2026Review
- Translating animal models of SARS-CoV-2 infection to vascular, neurological and gastrointestinal manifestations of COVID-19.Disease models & mechanisms · 2025Review
- NMDA receptor antagonists mitigate COVID-19-induced neuroinflammation and improve survival in a mouse model.Scientific reports · 2025Article
- A Disease Hidden in Plain Sight: Pathways and Mechanisms of Neurological Complications of Post-acute Sequelae of COVID-19 (NC-PASC).Molecular neurobiology · 2025Review
- Role of toll-like receptors in post-COVID-19 associated neurodegenerative disorders?Frontiers in medicine · 2025Review
- Smelling TNT: Trends of the Terminal Nerve.International journal of molecular sciences · 2024Review
- Brain Pathology in COVID-19: Clinical Manifestations and Potential Mechanisms.Neuroscience bulletin · 2024Review
- New evidence suggests SARS-CoV-2 neuroinvasion along the nervus terminalis rather than the olfactory pathway.Acta neuropathologica · 2024Article
- Unraveling the SARS-CoV-2 spike protein long-term effect on neuro-PASC.Frontiers in cellular neuroscience · 2024Article
- Seven-tesla magnetic resonance imaging of the nervus terminalis, olfactory tracts, and olfactory bulbs in COVID-19 patients with anosmia and hypogeusia.Frontiers in radiology · 2024Article
- Gray Matter Thickness and Subcortical Nuclear Volume in Men After SARS-CoV-2 Omicron Infection.JAMA network open · 2023Article
- SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice.Cell reports · 2023Article
- Olfactory dysfunction: A plausible source of COVID-19-induced neuropsychiatric symptoms.Frontiers in neuroscience · 2023Review
- COVID-19 and olfactory dysfunction: a looming wave of dementia?Journal of neurophysiology · 2022Review
- Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice.Veterinary pathology · 2022Article
- Dissecting the Molecular Mechanisms Surrounding Post-COVID-19 Syndrome and Neurological Features.International journal of molecular sciences · 2022Review
- The route of SARS-CoV-2 to brain infection: have we been barking up the wrong tree?Molecular neurodegeneration · 2022Article
- The olfactory nerve is not a likely route to brain infection in COVID-19: a critical review of data from humans and animal models.Acta neuropathologica · 2021Review
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3 authors at 2 institutions in 2 countries.
Funding
Abstract
Previous studies suggested that the SARS-CoV-2 virus may gain access to the brain by using a route along the olfactory nerve. However, there is a general consensus that the obligatory virus entry receptor, angiotensin converting enzyme 2 (ACE2), is not expressed in olfactory receptor neurons, and the timing of arrival of the virus in brain targets is inconsistent with a neuronal transfer along olfactory projections. We determined whether nervus terminalis neurons and their peripheral and central projections should be considered as a potential alternative route from the nose to the brain. Nervus terminalis neurons in postnatal mice were double-labeled with antibodies against ACE2 and two nervus terminalis markers, gonadotropin-releasing hormone (GnRH) and choline acetyltransferase (CHAT). We show that a small fraction of CHAT-labeled nervus terminalis neurons, and the large majority of GnRH-labeled nervus terminalis neurons with cell bodies in the region between the olfactory epithelium and the olfactory bulb express ACE2 and cathepsins B and L. Nervus terminalis neurons therefore may provide a direct route for the virus from the nasal epithelium, possibly via innervation of Bowman's glands, to brain targets, including the telencephalon and diencephalon. This possibility needs to be examined in suitable animal models and in human tissues.
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