TY - JOUR
T1 - Identification of brain-derived neurotrophic factor in nestin-expressing astroglial cells in the neostriatum of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine-treated mice
AU - Chen, L. W.
AU - Hu, H. J.
AU - Liu, H. L.
AU - Yung, K. K.L.
AU - Chan, Y. S.
N1 - Funding Information:
This work was supported by grants from the National Natural Science Foundation of China (No: 30371572 and 30218002) and the Research Grants Council of Hong Kong (No. N_HKBU202/02). Authors also thank Dr. N. H. Jing, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences, for gifting rabbit anti-nestin antibody, and the Developmental Studies Hybridoma Bank for supplying mouse anti-nestin antibody (R-401) that was developed under the auspices of the NICHD and maintained by The University of Iowa, USA.
PY - 2004/6
Y1 - 2004/6
N2 - Up-regulation of nestin expression was significantly induced in the caudate-putamen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice in our previous observation [Brain Res 925 (2002) 9]. We hypothesized that the nestin-expressing cells might play an important role in the pathogenesis of parkinsonian model, and characterization of these nestin-expressing cells was studied by RT-PCR, immunohistochemistry and semi-quantitative analysis for various markers of glial fibrillary acid protein (GFAP), S-100, neuronal nuclear specific protein (NeuN), β-tubulin, Ki-67 and brain-derived neurotrophic factor (BDNF) expression in MPTP-treated C57/BL mice. Firstly, significant increasing in both nestin protein and mRNA was found in MPTP-treated mice. Up-regulation of nestin expression started at day 1, peaked at day 3, and gradually went down at days 7-21 in the neostriatum after MPTP treatment. Secondly, double immunofluorescence indicated that almost all of nestin-positive cells exhibited GFAP (98%) or S-100 (96%)-immunoreactivity, whereas NeuN or β-tubulin was hardly detected in these nestin-positive cells. Thirdly, a minor population (7.0%) of nestin-positive cells showed Ki-67 (cell proliferation marker)-immunoreactivity, showing some of them went into cell mitotic state. Finally but more interestingly, a major population (86%) of nestin-expressing cells also exhibited immunoreactivity for BDNF, one neurotrophic factor. These results present time-dependent up-regulation of nestin expression in neostriatum, the proliferative and neurotrophic properties of nestin-expressing astroglial cells in MPTP-treated C57/BL mice. Taken together with previous observations, this study suggests that nestin-expressing activated astroglial cells, possibly partially through synthesizing and releasing neurotrophic factors such as BDNF in the basal ganglia, may play important roles in protection of nigrostriatal dopamine neurons and in the pathogenesis of Parkinson's disease in mammals.
AB - Up-regulation of nestin expression was significantly induced in the caudate-putamen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice in our previous observation [Brain Res 925 (2002) 9]. We hypothesized that the nestin-expressing cells might play an important role in the pathogenesis of parkinsonian model, and characterization of these nestin-expressing cells was studied by RT-PCR, immunohistochemistry and semi-quantitative analysis for various markers of glial fibrillary acid protein (GFAP), S-100, neuronal nuclear specific protein (NeuN), β-tubulin, Ki-67 and brain-derived neurotrophic factor (BDNF) expression in MPTP-treated C57/BL mice. Firstly, significant increasing in both nestin protein and mRNA was found in MPTP-treated mice. Up-regulation of nestin expression started at day 1, peaked at day 3, and gradually went down at days 7-21 in the neostriatum after MPTP treatment. Secondly, double immunofluorescence indicated that almost all of nestin-positive cells exhibited GFAP (98%) or S-100 (96%)-immunoreactivity, whereas NeuN or β-tubulin was hardly detected in these nestin-positive cells. Thirdly, a minor population (7.0%) of nestin-positive cells showed Ki-67 (cell proliferation marker)-immunoreactivity, showing some of them went into cell mitotic state. Finally but more interestingly, a major population (86%) of nestin-expressing cells also exhibited immunoreactivity for BDNF, one neurotrophic factor. These results present time-dependent up-regulation of nestin expression in neostriatum, the proliferative and neurotrophic properties of nestin-expressing astroglial cells in MPTP-treated C57/BL mice. Taken together with previous observations, this study suggests that nestin-expressing activated astroglial cells, possibly partially through synthesizing and releasing neurotrophic factors such as BDNF in the basal ganglia, may play important roles in protection of nigrostriatal dopamine neurons and in the pathogenesis of Parkinson's disease in mammals.
KW - nestin
KW - astrocyte
KW - neural progenitors
KW - basal ganglia
KW - MPTP
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=2942642117&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2004.04.020
DO - 10.1016/j.neuroscience.2004.04.020
M3 - Journal article
C2 - 15207328
AN - SCOPUS:2942642117
SN - 0306-4522
VL - 126
SP - 941
EP - 953
JO - Neuroscience
JF - Neuroscience
IS - 4
ER -