| Budget Amount *help |
¥2,500,000 (Direct Cost : ¥2,500,000)
Fiscal Year 1997 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1996 : ¥1,200,000 (Direct Cost : ¥1,200,000)
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| Research Abstract |
A.Neuronal death
We produced a polyclonal antibody against Bak, a protein promoting neuronal apoptosis, and thereby studied its expression in human brains by Western blotting and immunostaining. In 1996, we investigated the changes associated with development and aging, and demonstrated that the expression of Bak is high in the fetal and aged brains. In 1997, we comapared Bak immunoreactivity between Down syndrome and control patients. In Down syndrome brains, the aging-related upregulation of Bak occurred prematurely. Cerebral neurons became Bak-positive prior to the development of neurofibrillary changes.
B.Neuronal differentiation
We produced rabbit antibodies against the N-and C-terminal of tuberin, the product of the TSC2 gene responsible for tuberous sclerosis. In 1996, we demonstrated the expression of tuberin in control cerebra. During development, tuberin content increased with age. Tuberous sclerosis brains by contrast showed loss of tuberin, which was severe in both the hamartomatous lesions (cortical tuber and subependymal giant cell tumor) and histologically normal cortices. Tuberin immunoreactivity was also lost from the renal and cardiac hamartomas. In 1997, we observed a normal level of tuberin expression in focal cortical dysplasia, thereby indicating pathophysiological difference between tuberous sclerosis and cortical dysplasia.
C.Neuronal migration
We extended immunohistochemical studies of the LIS1 gene product (a 45k subunit of PAF acetylhydrolase), the defect of which being responsible for the Miller-Dieker lissencephaly syndrome. In 1996, we studied the expression of LIS1 in various migration disorders, and demonstrated that the loss of LIS1 is specific to the syndrome. In 1997, we immunostained human fetal brains and observed strong labeling of the ventricular neuroepithlium and Cajal-Retzius cells.
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