| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
Aralar is a brain-and muscle-type mitochondrial aspartate-glutamate carrier, and related to the transport of aspartate from mitochondria to cytosol, and to the transfer of cytosolic reducing equivalents into mitochondria as a member of the malate-aspartate NADH shuttle.
The aralar deficient mice, generated by a gene-trap method, revealed the strong growth-retardation, generalized tremoring, and motor coordination defects, and died at approximately 20 days after birth.
Histological analysis of the brain in the aralar deficient mice at 18-20 days showed a prominent hypomyelination throughout the telencephalon and diencephalon, such as the corpus callosum, white matter of the cerebral cortex, and internal capsule. However, no prominent change in the neuronal numbers, morphology, or cytoarchitecture was observed in the brain of the aralar deficieat mice, except these mice had enlarged the lateral ventricles. Immunocytochemical study using the primary antibody to the myelin basic protein (MBP
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) confirmed the results of the myelin staining, snowing a decrease in the intensity and numbers of the immunostained fibers throughout the telencephalon and diencephalon. The contents of the myelin lipid precursor, N-acetylaspartate, and of aspartate were drastically decreased in the brain of aralar deficient mice. These results suggest that aralar plays an important role in the myelin formation by providing aspartate for the synthesis of N-acetylaspar tate.
By using the immunocytochemical study, the level of the type I glutamate receptor-like immunoreactivity was observed to be upregulated in the hippocampus area and dentate gyrus of the aralar deficient mice as compared to that of the wild-type animals. The number of the tryptophan hydroxylase-like immunostained neuronal somata located in the raphe nuclei of the brain stem of the aralar deficient mice was slightly decreased than that of the wild-type mice. In order to study the neuronal activity of the orexinergic neurons, the percentage of the expression of c-Fos protein was evaluated by using double immunocytochemical staining of c-Fos protein-and orexin-like immunoreactivity in the hypothalamus of the aralar deficient and wild-type animals. The double immunocytochemical study showed the percentage of c-Fos positive orexinergic neurons in the aralar deficient mice was very much higher than those of the wild-type animals. Less
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