《by Astrocytes》.pdfVIP

The Journal of Neuroscience, March 26, 2008 • 28(13):3277–3290 • 3277 Neurobiology of Disease Expanded-Polyglutamine Huntingtin Protein Suppresses the Secretion and Production of a Chemokine (CCL5/RANTES) by Astrocytes 1,2 3 2 2 3 2 4 Szu-Yi Chou, Ju-Yun Weng, Hsing-Lin Lai, Fang Liao, Synthia H. Sun, Pang-Hsien Tu, Dennis W. Dickson, and Yijuang Chern1,2,3 1 2 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 104, Taiwan, Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 115, Taiwan, 3 4 Institute of Neuroscience, National Yang-Ming University, Taipei 112, Taiwan, and Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224 Huntington’s disease (HD) is a hereditary neurological disease caused by expended CAG repeats in the HD gene, which codes for a protein called Huntingtin (Htt). The resultant mutant Huntingtin (mHtt) forms aggregates in neurons and causes neuronal dysfunction. In astrocytes, the largest population of brain cells, mHtt also exists. We report herein that astrocyte-conditioned medium (ACM) collected from astrocytes of R6/2 mice (a mouse model of HD) caused primary cortical neurons to grow less-mature neurites, migrate more slowly, and exhibit lower calcium influx after depolarization than those maintained in wild-type (WT) ACM. Using a cytokine antibody array and ELISA assays, we demonstrated that the amount of a chemokine [chemokine (C-C motif) ligand 5 (CCL5)/regul