ABSTRACT
Objective To investigate the effect of cholesterol on the proliferation and differentiation of neural stem cells (NSCs) in ob/ob obese mice, and to explore the possible mechanism of central nervous systym dysfunction caused by obesity. Methods Selected 64-month-old ob/ob and wild type (WT) mice, and cell proliferation antigen (Ki67) and doublecortin (DCX) immunofluorescenct staining were used to detect ob/ob mice lateral ventricle subventricular zone (SVZ) neurogenesis level. Cultured SVZ NSCs isolated from 184-month-old ob/ob and WT mice, and BrdU incorporation experiment and β-III-tubulin (Tuj1) immunofluorescent staining were employed to detect the self-renewal and differentiation ability of NSCs. Matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI- MS)was used to detect the lipid distribution in 4-month-old ob/ob and WT mice brain tissues, and measure the changes of cholesterol(ST) content and the expression genes related to cholesterol synthesis. Cultured 15 WT postnatal day 0(P0) mouse SVZ NSCs in vitro and electrotransfected with the small interfering RNA(siRNA) sequence of cholesterol synthesis rate-limiting enzyme 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (Hmgcr) verified the knockdown efficiency, to detecte the effect of Hmgcr gene knockdown on NSCs by BrdU incorporation experiment and Tuj1 immunofluorescent staining. Results Compared with the WT mice, the number of Ki67