title: The effect of Ndrg2 expression on astroglial activation.
abstract: N-myc downstream-regulated gene 2 (Ndrg2) is a differentiation- and stress-associated molecule predominantly expressed in astrocytes in the central nervous system (CNS). To study the expression and possible role of Ndrg2 in quiescent and activated astrocytes, mice were administrated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP), a Parkinson disease (PD)-related neurotoxin which causes both neurodegeneration and glial activation. Immunohistological analysis revealed that Ndrg2 was highly expressed in both types of astrocytes, but less so in astrocytes during the early process of activation. Ndrg2 was also expressed in astrocyte-like cells, but not in neurons, in human brains from PD and Cortico-basal degeneration (CBD) patients. In cultured astrocytes, gene silencing of Ndrg2 significantly enhanced the numbers of 5-bromo-2'-deoxy-uridine (BrdU)-incorporated and proliferating cell nuclear antigen (PCNA)-positive cells, and reduced the length of cell processes and the amount of F-actin. In contrast, adenovirus-mediated overexpression of Ndrg2 significantly reduced the numbers of BrdU-incorporated and PCNA-positive cells, and enhanced the amount of F-actin. Fractionation and immunocytochemical analysis further revealed that Ndrg2 was located in different cellular fractions including the cytosol and cell surface membranes. These results suggest that Ndrg2 may regulate astroglial activation through the suppression of cell proliferation and stabilization of cell morphology.
authors.affiliation: Department of Legal Medicine, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takeichi
authors.forename: Mika
authors.initials: M
authors.lastname: Takarada-Iemata
authors.forename: Koji
authors.initials: K
authors.lastname: Hashida
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sudo
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Okuda
authors.forename: Koichi
authors.initials: K
authors.lastname: Kokame
authors.forename: Taku
authors.initials: T
authors.lastname: Hatano
authors.forename: Masashi
authors.initials: M
authors.lastname: Takanashi
authors.forename: Sayaka
authors.initials: S
authors.lastname: Funabe
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.forename: Osamu
authors.initials: O
authors.lastname: Kitamura
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kitao
authors.forename: Osamu
authors.initials: O
authors.lastname: Hori
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001483:Base Sequence; D049109:Cell Proliferation; D006801:Humans; D008969:Molecular Sequence Data; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C466228:NDRG2 protein, human; D025521:Tumor Suppressor Proteins