RXR agonist bexarotene modulates the cell‐fate and migration abilities of adult neural stem cells in vitro
نویسندگان
چکیده
Background Targeting the nuclear RXR receptors has been associated with brain-specific roles striking therapeutic potential for Alzheimer’s Disease (AD), similar observations to its dimerization partners such as LXR and PPAR whose responses are also under influence of activation. Treatment bexarotene, a selective agonist, leads significant recovery cognitive loss in variable mice AD-like models - activates neurodevelopment plasticity pathways adult brains. Our hypothesis is that neural stem cells (NSC) residing brain directly respond leading improved neurogenesis other effects compatible recovery. Method We employed an vitro strategy using NSCs isolated from subventricular zone rats’ Adult NCSs were treated bexarotene neurosphere proliferative stage differentiated states, cell-fate consequences evaluated through morphometric analysis immunofluorescence cell markers. Result In stages, bexarotene-treated exhibited increased outgrowth neurospheres. Bexarotene treatment led changes fate differentiating cells, marked increase GFAP staining after differentiation. Relatively newborn neurons, we found decrease DCX positive neuroblasts treatment. However, Tuj1 neurons was preserved. Neurite number, length, bifurcations unaffected by bexarotene. Conclusion increasing migration abilities generating more GFAP+ cells. Results indicate activation preserves, but does not activate, neuronal differentiation neurite complexity. The significance glial population, well decreased DCX+ young remains be unrevealed. Finally, did observe clear bexarotene-induced proliferation, effect over pluripotency these needs further investigation. These findings address gap our knowledge regarding substantiating search possible application RXR-based approaches AD.
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ژورنال
عنوان ژورنال: Alzheimers & Dementia
سال: 2023
ISSN: ['1552-5260', '1552-5279']
DOI: https://doi.org/10.1002/alz.065145