GDNF is a major component of trophic activity in DA-depleted striatum for survival and neurite extension of DAergic neurons

• Published in: Brain research 2001-10, Vol.916 (1), p.76-84
• Main Authors: Nakajima, Keiya, Hida, Hideki, Shimano, Yasunobu, Fujimoto, Ichiro, Hashitani, Takeshi, Kumazaki, Michiko, Sakurai, Terumi, Nishino, Hitoo
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes - metabolism; bFGF; Biological and medical sciences; Brain-Derived Neurotrophic Factor - metabolism; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Extracts - chemistry; Cell Extracts - pharmacology; Cell physiology; Cell Survival - drug effects; Cell Survival - physiology; Cells, Cultured - cytology; Cells, Cultured - drug effects; Cells, Cultured - metabolism; Dopamine - deficiency; Dopaminergic neurons; Fibroblast Growth Factor 2 - metabolism; Fibroblast Growth Factor 2 - pharmacology; Fundamental and applied biological sciences. Psychology; GDNF; Glial Cell Line-Derived Neurotrophic Factor; Glial Fibrillary Acidic Protein - metabolism; Heparin; Immunohistochemistry; Microtubule-Associated Proteins - metabolism; Molecular and cellular biology; Neostriatum - metabolism; Neostriatum - physiopathology; Nerve Growth Factors; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - pharmacology; Neurites - drug effects; Neurites - metabolism; Neurites - ultrastructure; Neuroprotective Agents - metabolism; Neuroprotective Agents - pharmacology; Neurotrophin 3 - metabolism; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; Parkinson Disease - physiopathology; Parkinson’s disease; Rats; Rats, Wistar; Responses to growth factors, tumor promotors, other factors; Striatal tissue extracts; Substantia Nigra - drug effects; Substantia Nigra - growth & development; Substantia Nigra - metabolism; Trophic factor
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)02866-9

Extracts from dopamine (DA)-depleted striatal tissue (lesion extract) and from intact striatal tissue (intact extract) were prepared, and trophic activities in these extracts were evaluated using survival and neurite extension of DAergic neurons as indices. Levels of brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor (bFGF), glial cell-line derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) in extracts were measured using enzyme-linked immunosorbent assay (ELISA). The lesion extract exhibited a stronger trophic activity on survival and neurite extension of DAergic neurons than intact extract. In lesion extract, bFGF was slightly and GDNF was significantly increased, while BDNF and NT-3 were the same level in each extract. The peak increase of bFGF and GDNF was during 2 to 3 weeks after DA depletion. Trophic activity of extract was strongly attenuated after immunoprecipitation of GDNF and partly attenuated after immunoprecipitation of bFGF. In parallel immunohistological study, no significant variations were found for striatal microtubule-associated protein-2 (MAP-2)- nor OX-41-immunoreactive cells, while the number of strongly labeled glial fibrillary acidic protein (GFAP)-immunoreactive cells were increased in DA-depleted striatum, suggesting reactive gliosis. Data suggest that bFGF is a minor, while GDNF is a major component of trophic activity for DAergic neurons in DA-depleted striatum, and increased bFGF and GDNF levels may be mediated partly by reactive gliosis.