Tamoxifen exerts direct and microglia-mediated effects preventing neuroinflammatory changes in the adult mouse hippocampal neurogenic niche.
Fiche publication
Date publication
mars 2024
Journal
Glia
Auteurs
Membres identifiés du Cancéropôle Est :
Dr KREZEL Wojciech
Tous les auteurs :
Crisci I, Bonzano S, Nicolas Z, Dallorto E, Peretto P, Krezel W, De Marchis S
Lien Pubmed
Résumé
Tamoxifen-inducible systems are widely used in research to control Cre-mediated gene deletion in genetically modified animals. Beyond Cre activation, tamoxifen also exerts off-target effects, whose consequences are still poorly addressed. Here, we investigated the impact of tamoxifen on lipopolysaccharide (LPS)-induced neuroinflammatory responses, focusing on the neurogenic activity in the adult mouse dentate gyrus. We demonstrated that a four-day LPS treatment led to an increase in microglia, astrocytes and radial glial cells with concomitant reduction of newborn neurons. These effects were counteracted by a two-day tamoxifen pre-treatment. Through selective microglia depletion, we elucidated that both LPS and tamoxifen influenced astrogliogenesis via microglia mediated mechanisms, while the effects on neurogenesis persisted even in a microglia-depleted environment. Notably, changes in radial glial cells resulted from a combination of microglia-dependent and -independent mechanisms. Overall, our data reveal that tamoxifen treatment per se does not alter the balance between adult neurogenesis and astrogliogenesis but does modulate cellular responses to inflammatory stimuli exerting a protective role within the adult hippocampal neurogenic niche.
Mots clés
LPS, adult neurogenesis, astrogliogenesis, dentate gyrus, microglia, neuroinflammation, radial glial‐like cells
Référence
Glia. 2024 03 21;: