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: Toshiaki Takeichi, Mika Takarada-Iemata, Koji Hashida, Hirofumi Sudo, Tomohiko Okuda, Koichi Kokame, Taku Hatano, Masashi Takanashi, Sayaka Funabe, Nobutaka Hattori, Osamu Kitamura, Yasuko Kitao, Osamu Hori
• Journal: Neurochemistry international (Neurochem Int) Vol. 59 Issue 1 Pg. 21-7 (Aug 2011) ISSN: 1872-9754 [Electronic] England
• PMID: 21672576 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• NDRG2 protein, human
• Tumor Suppressor Proteins

Topics

• Animals
• Astrocytes (cytology, metabolism)
• Base Sequence
• Cell Proliferation
• Humans
• Molecular Sequence Data
• RNA Interference
• Rats
• Rats, Wistar
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Suppressor Proteins (genetics)