Dépôt numérique

Glutamate excitotoxicity is involved in motor dysfunctions and paralysis following infection by a human respiratory coronavirus

Brison, Élodie; Jacomy, Hélène; Desforges, Marc et Talbot, Pierre J. ORCID logoORCID: https://orcid.org/0000-0003-4203-7744 (2012). Glutamate excitotoxicity is involved in motor dysfunctions and paralysis following infection by a human respiratory coronavirus In: 11th International Symposium on NeuroVirology (ISNV) Meeting, May 29-June 2, 2012, New York.

Ce document n'est pas hébergé sur EspaceINRS.


Human coronaviruses (HCoV) are respiratory pathogens. We have reported that strain HCoV-OC43 can infect human neuronal and glial cells, activate neuroinflammatory and neurodegenerative mechanisms, thus possibly be involved in neurological disease of unknown etiology, such as multiple sclerosis (MS). Using an animal model, we reported that a viral persistence-associated point mutation in the viral spike S glycoprotein (Y241H) modified neuropathology from encephalitis to MS-related hind-limb paralysis. Viral CNS infections may induce excitotoxicity, a pathological process by which neurons are damaged and die following an excessive stimulation by the glutamate neurotransmitter on its specific ionotropic receptors (AMPAr and NMDAr). We have previously shown that the paralytic disease induced by the HCoV-OC43 S mutant involves (AMPAr)-mediated glutamate excitotoxicity. Given that overactivation of the N-methyl-D-aspartic acid receptor (NMDAr) may also lead to excitotoxicity, pharmacological research has focused on the development of NMDAr antagonists. Memantine is one such molecule: it modulates glutamate excitotoxicity and is widely used for treatment of human neurological disorders such as MS. We now show that a low dose of memantine (1 μg/g body weight) improved clinical scores related to paralytic disease in mice infected by the HCoV-OC43 S mutant, without affecting viral replication. However, a 10-fold higher dose attenuated both the clinical scores, related to paralysis and motor dysfunctions, and mortality rates. Memantine attenuated virus replication in a dosedependent manner in cell culture, compared to dizocilpine (MK-801), another NMDAr antagonist, which neither affected virus replication nor reduced mortality rates. Studies are currently underway to investigate the mechanisms underlying such dose-dependent neuroprotective and antiviral activities of memantine. (Supported by operating grant MT-9203 from Canadian Institutes of Health Research (CIHR) to Pierre J. Talbot, who is the holder of the Tier 1 (Senior) Canada Research Chair in Neuroimmunovirology award. Elodie Brison acknowledges a doctoral studentship from the MS Society of Canada).

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Affiche scientifique P35 Journal of Neurovirology 18(suppl.1):17-18
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 28 janv. 2024 14:55
Dernière modification: 28 janv. 2024 14:55
URI: https://espace.inrs.ca/id/eprint/14118

Gestion Actions (Identification requise)

Modifier la notice Modifier la notice