Development investigation for enhancement of regeneration and amelioration of function of the damaged peripheral nerves by medical regulation of neurotrophin synthesis.

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(1) EFFECTIVE IMPROVEMENT ON NEURONAL DYSFUNCTION BY ADMINISTRATION OF 4-METHYLCATECHOL (4-MC) IN DIABETIC OR ACRYLAMIDE-INDUCED PERIPHERAL NEUROPATHY.Streptozotocin (STZ) -induced diabetic rats showed a reduction in motor nerve conduction velocity (MNCV), myelinated axon diameter, and nerve growth factor (NGF) content in the sciatic nerve. 4-MC treatment started 4 weeks after the STZ injection resulted in improvements on all of these damages in diabetic rats. In acrylamide (ACR) -induced neuropathy, when ACR and 4-MC were coadministered intraperitoneallys, improved clinical signs, and more NGF content in the sciatic nerves, faster MNCV,and greater myelinated fiber density than in rats given ACR alone were found. These findings suggest that a decreased NGF level may be involved in the pathogenesis of diabetic and ACR-induced neuropathies and that 4-MC treatment could be a useful therapy.(2) PREPARATION OF ANTIBODIES SPECIFICALLY RECOGNIZE BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) AND NEUROTROPHIN-3 (NT-3).Quantitative methods to detect respective neurotrophins are necessary to evaluate theirroles in regeneration and functional repair of perigheral nerves. We succeeded to raise antibodies in chicken specifically recognize BDNF or NT-3. Two-site enzyme immunoassaies using these antibodies could detect BDNF and/or NT-3 as low as a concentration of a few pg/ml.(3) REGULATION OF BDNF EXPRESSION IN NEURONS CULTURED FROM CHICK DORSAL ROOT GANGLIA (DGR).Recent reports localize BDNF mRNA in the neurons cultured from chick embryo DRG,which are known responsive to BDNF.To estimate physiological roles of BDNF expression in the DRG neurons, we investigated changes of BDHF-like immunoreactivity during depolarization, and found that it caused a transient decrease in expression of BDNF protein. This suggests that stimuli-transmission followd by depolarization suppresses BDNF synthesis in DRG neurons during maturation of peripheral sensory system.