| Title: |
Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death |
| Authors: |
Sauve, Florent; Nampoothiri, Sreekala; Clarke, Sophie; Fernandois, Daniela; Ferreira Coêlho, Caio Fernando; Dewisme, Julie; Mills, Edouard; Ternier, Gaetan; Cotellessa, Ludovica; Iglesias-Garcia, Cristina; Mueller-Fielitz, Helge; Lebouvier, Thibaud; Perbet, Romain; Florent, Vincent; Baroncini, Marc; Sharif, Ariane; Ereño-Orbea, June; Mercado-Gómez, Maria; Palazon, Asis; Mattot, Virginie; Pasquier, Florence; Catteau-Jonard, Sophie; Martinez-Chantar, Maria; Hrabovszky, Erik; Jourdain, Mercé; Deplanque, Dominique; Morelli, Annamaria; Guarnieri, Giulia; Storme, Laurent; Robil, Cyril; Trottein, François; Nogueiras, Ruben; Schwaninger, Markus; Pigny, Pascal; Poissy, Julien; Chachlaki, Konstantina; Maurage, Claude-Alain; Giacobini, Paolo; Dhillo, Waljit; Rasika, S.; Prevot, Vincent |
| Contributors: |
Lille Neurosciences & Cognition - U 1172 LilNCog; Imperial College London; Universidade de Santiago de Compostela Spain USC; Universität zu Lübeck = University of Lübeck Lübeck; Recherche translationnelle sur le diabète - U 1190 RTD; Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 CIC Lille; Università degli Studi di Firenze = University of Florence UniFI; Hôpital Jeanne de Flandre Lille; Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 CIIL; Centre Hospitalier Régional Universitaire CHU Lille CHRU Lille; Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576 |
| Publisher Information: |
Elsevier |
| Publication Year: |
2024 |
| Collection: |
LillOA (Lille Open Archive - Université de Lille) |
| Description: |
BackgroundWe have recently demonstrated a causal link between loss of gonadotropin-releasing hormone (GnRH), the master molecule regulating reproduction, and cognitive deficits during pathological aging, including Down syndrome and Alzheimer's disease. Olfactory and cognitive alterations, which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline.MethodsWe explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue.FindingsWe found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin, favouring post-COVID cognitive or neurological symptoms, and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes. Furthermore, GnRH neurons themselves were dying in all patient brains studied, dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection.InterpretationPutative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive, metabolic, and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/octet-stream |
| Language: |
English |
| Relation: |
Analyse tridimensionnelle du développement des systèmes moteur et nerveux périphérique humains; ULNE; EBioMedicine; http://hdl.handle.net/20.500.12210/89583 |
| Availability: |
https://hdl.handle.net/20.500.12210/89583 |
| Rights: |
Attribution-NonCommercial-NoDerivs 3.0 United States ; info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.AD874ED2 |
| Database: |
BASE |