|Budget Amount *help
¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 1998 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1997 : ¥1,900,000 (Direct Cost : ¥1,900,000)
Glial cell line-derived neurotrophic factor (GDNFR) has been shown to have trophic effect upon dopaminergic neurons and motoneurons in the anterior horn cells of spinal cord. In the present research project we have planned to localize GDNFR in the brain immunohistochemically and examine whether GDNFR is involved in the pathophysiology of neurodegenerative disease such as Parkinson's disease, amyotrophic lateral sclerosis, multiple system atrophy and Alzheimer's disease.
We have firstly developed an anti-peptide antibody against synthetic peptide of amino-terminal portion of GDNFR The antibody recognized a single protein of molecular weight of 80 kDa in the rat brain homogenate. The preabsorption of the antibody with the immunogen completely abolished the immunostaining in the western blot lane. The immunohistochemical study has demonstrated GDNFR-immunoreactivity exclusively in neurons and no glial cells were immunopositive. The immunopositive neuronal somata were found throughout the rat brain. In the neocortex the positive neurons were distributed in the layer II through to layer VI.Pyramidal and non-pyramidal cell were both labeled. In the basal forebrain, numerous large sized neurons were immunolabeled in the nucleus of Meynert, medial septal nucleus, nucleus, of diagonal band of Broca and ventral pallidum. Numerous neuronal somata were found also in nuclei of the hind brain, including substantia nigra, raphe, and cochlear nucleus. Thus, GDNF responsive neurons appear to be distributed more widespread in the rat brain than previously described.