%0 Journal Article %T Inflammation-induced subventricular zone dysfunction leads to olfactory deficits in a targeted mouse model of multiple sclerosis. %+ Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM) %+ Perception et Mémoire %+ Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) %+ Institute for Protein Research [Osaka] %+ Instituto Cavanilles Biodiversidad y Biologia Evolutiva %+ CHU Pitié-Salpêtrière [AP-HP] %A Tepavčević, Vanja %A Lazarini, Françoise %A Alfaro-Cervello, Clara %A Kerninon, Christophe %A Yoshikawa, Kazuaki %A Garcia-Verdugo, José Manuel %A Lledo, Pierre-Marie %A Nait-Oumesmar, Brahim %A Baron-van Evercooren, Anne %Z This work was supported by INSERM, the European Leukodystrophy Association (ELA), Ecole des Neurosciences de Paris (ENP), French Society for Multiple Sclerosis (ARSEP), Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, Red de Terapia Celular, Consellería de Educación (PROMETEO), and the life insurance company Aprionis. V. Tepavcevic was supported by UPMC, Fondation pour la Recherche Médicale (FRM), Novartis, and COST Action MYELINET BM0604 and NEURINFNET BM0603. B. Nait-Oumesmar and A. Baron-Van Evercooren are recipients of a Contrat d’Interface AP-HP (Fédération de Neurologie, Hôpital Pitié-Salpêtrière, Paris). %< avec comité de lecture %@ 0021-9738 %J Journal of Clinical Investigation %I American Society for Clinical Investigation %V 121 %N 12 %P 4722-34 %8 2011-11-30 %D 2011 %R 10.1172/JCI59145 %M 22056384 %K adult neurogenesis %K olfaction %K multiple sclerosis %Z Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Journal articles %X Neural stem cells (NSCs) persist in defined brain niches, including the subventricular zone (SVZ), throughout adulthood and generate new neurons destined to support specific neurological functions. Whether brain diseases such as multiple sclerosis (MS) are associated with changes in adult NSCs and whether this might contribute to the development and/or persistence of neurological deficits remains poorly investigated. We examined SVZ function in mice in which we targeted an MS-like pathology to the forebrain. In these mice, which we refer to herein as targeted EAE (tEAE) mice, there was a reduction in the number of neuroblasts compared with control mice. Altered expression of the transcription factors Olig2 and Dlx2 in the tEAE SVZ niche was associated with amplification of pro-oligodendrogenic transit-amplifying cells and decreased neuroblast generation, which resulted in persistent reduction in olfactory bulb neurogenesis. Altered SVZ neurogenesis led to impaired long-term olfactory memory, mimicking the olfactory dysfunction observed in MS patients. Importantly, we also found that neurogenesis was reduced in the SVZ of MS patients compared with controls. Thus, our findings suggest that neuroinflammation induces functional alteration of adult NSCs that may contribute to olfactory dysfunction in MS patients. %G English %2 https://pasteur.hal.science/pasteur-01300312/document %2 https://pasteur.hal.science/pasteur-01300312/file/JCI59145.pdf %L pasteur-01300312 %U https://pasteur.hal.science/pasteur-01300312 %~ INSERM %~ PASTEUR %~ UPMC %~ CNRS %~ APHP %~ ICM %~ UPMC_POLE_4 %~ SORBONNE-UNIVERSITE %~ SU-INF-2018 %~ SU-MEDECINE %~ SU-MED %~ SU-TI %~ ALLIANCE-SU %~ FRM