title: Suppression of cytochrome P450 reductase expression promotes astrocytosis in subventricular zone of adult mice.
abstract: The aim of this study was to determine the role of NADPH-cytochrome P450 reductase (CPR) and CPR-dependent enzymes in neural stem cell (NSC) genesis in the brain. A mouse model with globally suppressed Cpr gene expression (Cpr-low mouse) was studied for this purpose. Cpr-low and wild-type (WT) mice were compared immunohistochemically for the expression of markers of cell proliferation (Ki67), immature neurons (doublecortin, DCX), oligodendrocytes (oligodendrocyte transcription factor 2, OLIG2), and astrocytes (glial fibrillary acidic protein, GFAP) in the SVZ, and for the in vitro capability of their SVZ cells to form neurospheres and differentiate into astrocytes. We found that the abundance of SVZ cells that are positive for Ki67 or GFAP expression, but not the abundance of SVZ cells that are positive for DCX and OLIG2 expression, was significantly increased in Cpr-low mice, at various ages, compared with WT mice. Furthermore, extents of astrocyte differentiation and growth, but not neurosphere formation, from SVZ cells of the Cpr-low mice were significantly increased, compared with WT mice. These results suggest that CPR and CPR-dependent enzymes play a role in suppressing astrocytosis in the SVZ of adult mice.
authors.affiliation: Research Center for Biochemistry and Molecular Biology, Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China.
authors.forename: Yunyi
authors.initials: Y
authors.lastname: Yao
authors.forename: Senyan
authors.initials: S
authors.lastname: Liu
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Weiping
authors.initials: W
authors.lastname: Yuan
authors.forename: Xinxin
authors.initials: X
authors.lastname: Ding
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.forename: Qin
authors.initials: Q
authors.lastname: Shen
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000201:enzymology* / Q000473:pathology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D000089662:Doublecortin Protein; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005911:Gliosis / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D003577:Cytochrome P-450 Enzyme System
keywords: Astrocytosis; CNS; CPR; Cytochrome P450 reductase; DCX; DG; GFAP; IHC; Mice; NADPH-cytochrome P450 reductase; NSC; Neural stem cells; OLIG2; P450 or CYP; SVZ; Subventricular zone; WT; central nerve system; cytochrome P450; dentate gyrus; double cortin; glial fibrillary acidic protein; immunohistochemistry; neural stem cell; oligodendrocyte transcription factor 2; subventricular zone; wild type