| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
1. For the mutant mice of GM2/GD2 Synthase gene lacking complex gangliosides (1) pathological analysis on neuro-degeneration with aging, and (2) analysis on molecular mechanisms for the degeneration were performed. First of all, for the peripheral nerve degeneration marked degeneraion of sciatic nerves, apoptosis of neurons in the dorsal root ganglia, death of neurons in the dorsal horn of the spinal cord, and enlargement of glia cells were found. In the analysis with electron microscopy, extension and enlargement of astrocytes and engulfment of blood vessels with ie projection of astrocytes were observed. Furthermore, morpholoicafchanged in the synaptic vesicles and synapse formation (spine type or dendrite type) were detected. These abnorrX changes became definite in the mutant mice after 35 weeks old (male) or 45 weeks oldI fSmaleV and neurological abnormal findings such as gait disturbance were simultaneously found.nd 4S RNA was extracted from the mutaut and wild type mice at approximately 25 weeks old, when theneurological abnormalities and pathological changes were not yet obvious, to analyze the changes in the expression levels of genes in the mutant mice. Preparing cDNAs, subtraction and differential hybridization were performed, resulting in the detection of about 30 colnes shich showed marked down-regulation in the mutant mice. Among them, genes associated with mitochondrial membrane enzymes, protease genes, and transciption factor genes were included. Implication of those gene products in the degeneration is now under investigation.
2. For the mutant mice of GD3 synthase gene lacking b-series gangliosides, (1) process of neuro- degeneration and (2) alteration in the regeneration potential were analyzed. La the mutant mice degeneration of the peripheral nerves was not definite, but marked reduction in the regeneration of lesioned nerves.
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