| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
The Bral1/Hapln2 proteins are expressed specifically at the nodes of Ranvier in the central nervous system and supposed to be important for the maintenance of matrix molecules by stable binding on the hyaluronan. To explore the role of the extranodal matrices on the saltatory conduction, we analyzed the Bral1/Hapln2 knockout mice.
1.Immunohistochemical and electronmicroscopic analysis
There was no obvious alteration on the formation of paranodes, which is consisted of glial cell (oligodendrocyte) and neuron (axon) interactions. There was also no obvious effect on the clustering of Na+ channels, which is essential for the production of action potentials and propagation of the signals.
2.Electrophiological analysis
However, when we compared the speed of propagation of action potentials on the optic nerves via electrophysiological measurement, there was a significant difference between wild type and Bral1/Hapln2 deficient mice. To figure out those differences, we investigated further the diff
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erences of the extranodal matrices as well as the attachment of the endofoot of astrocyte at the node. We could find the mislocalization of several ECM molecules including versican (a chondroitin sulfate proteoglycan), tenascin-R and others in the Bral1/Hapln2 deficient mice. During those analyses, we could find one ECM molecule, which has not reported so far to localize at the nodes of Ranvier, is colocalizing and stabilized with Bral1/Hapln2. Nevertheless, there was no obvious difference of the attachment of the endofoot of the astrocyte.
3.Possible physiological roles of the extranodal matrix
Collectively, there was no obvious difference in formation of paranodes and astrocyte foot process via glial and neuronal cell interactions. We could only observe the difference in the formation of the structure of extranodal matrices. Therefore, we assume that the complex of matrix molecules consisting of chondroitin sulfate proteoglycans and other glycoprotein is contributing to the maintenance of the microenvironment around the nodes. Possibly, it can serve as a Na+ ion-pool, which is important for generating the action potentials via influx through the voltage dependent Na+ channels at the nodes. Less
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