MITSUMA Terunori DEPARTMENT OF INTERNAL MEDICINE PROFESSOR, 医学部, 教授 (00111857)
KIMATA Kouji INSTITUTE FOR MOLECULAR SCIENCE OF MEDICINE PROFESSOR, 分子医科学研究所, 教授 (10022641)
TERAO Sinichi DEPARTMENT OF INTERNAL MEDICINE ASSISTANT, 医学部, 助手 (50188661)
KUMAZAWA Kazuhiko DEPARTMENT OF INTERNAL MEDICINE ASSISTANT, 医学部, 助手 (20178065)
|Budget Amount *help
¥1,800,000 (Direct Cost : ¥1,800,000)
Fiscal Year 1992 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1991 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1990 : ¥700,000 (Direct Cost : ¥700,000)
Gene expression of the neurotrophic factors and their receptors and related molecules was analyzed in the human, rat and mouse peripheral nervous system, particularly in the process of the peripheral nerve degeneration and regeneration. The molecules analyzed in this study included NGF, BDNF, LNGFR, trk,trkB, laminin A, B_1, B_2 chains and collagen type I, III, IV. Expression levels of mRNA for these molecules in the tissues were determined by Northern blot analysis. The findings obtained are as follows :
NGF, BDNF, LNGFR, laminin B_1, B_2, collagen type I, III, IV were synthesized in cultured Schwann cells inculture, and their mRNA levels were up- or down-regulated by exogenously administered cAMP analogues or by the contact with sensory neurons.
Human DRG neurons and sympathetic neurons express LNGFR, trk, trkBmRNAs, and which were likely down-regulated in the cases with neuropathy particularly in axonal type.
LNGFR were up- regulated and laminin B_1, B_2 were down-reglated in the axonal nerve lesions of humans as well as mouse and rats, but which were reversely reglated in associated with nerve regeneration
Neurite arborization (sprouting) was significantly enhanced by NGF on the post-matured DRG neurons, and this ability was well retained in the aging process, which may have corresponded to the well preserved functional NGF receptor (trk) expression on the aged these neurous. Those finding confirmed that these neurotrophic molecules and their receptors are up-or down-regulated in association with peripheral nerve de-and regeneration suggesting their significant roles in the neuropathies. Further study on the signal mechanism for these gene expressions is now required.