著者
石川 敏三 仲西 修 掛田 崇寛 山本 美佐 古川 昭栄 伊吹 京秀 徳田 信子 石川 浩三 鈴木 秀典
出版者
山口大学
雑誌
基盤研究(C)
巻号頁・発行日
2012-04-01

慢性疼痛はしばしば不安や鬱を併発し、極めて難治性である。そこで、痛覚ー情動系における分子メカニズムを解明し、また神経栄養因子(BDNF)治療応用について検討した。その結果、前帯状回や脳幹部(網様体)におけるモノアミン変調に随伴したBDNFの機能低下が慢性疼痛や気分障害に関連すること、またカテーコール化合物や磁気治療の有用性が判明した。慢性疼痛の治療法に新たな指針を提唱するものと考えられる。
著者
古川 昭栄
出版者
公益社団法人 日本薬学会
雑誌
YAKUGAKU ZASSHI (ISSN:00316903)
巻号頁・発行日
vol.135, no.11, pp.1213-1226, 2015 (Released:2015-11-01)
参考文献数
71
被引用文献数
1 3

The author has studied nerve growth factor (NGF) and its family of neurotrophic factors (neurotrophins) for over 40 years. During the first 20 years, my laboratory established a highly sensitive enzyme immunoassay for NGF and analyzed the regulatory mechanism of NGF synthesis in cultured primary cells. Fibroblast cells cultured from peripheral organs such as the heart and astrocytes from the brain produced a substantial amount of NGF in a growth-dependent manner. Furthermore, synthesis of NGF in these cells could be upregulated by catechol compounds including catecholamines. This observation might explain a physiological relation between the level of NGF mRNA and the density of innervation in the peripheral sympathetic nervous systems. Over the subsequent 20 years, my laboratory investigated the physiological functions of neurotrophic factors, including neurotrophins, during development or post-injury and found that brain-derived neurotrophic factor (BDNF) plays a role in the formation of the laminar structure of the cerebral cortex. In addition, my laboratory discovered that endogenous glial cell line-derived neurotrophic factor (GDNF) contributes to the amelioration of motor activity after spinal cord injury. Therefore we aimed to develop low-molecular weight compounds that generate neurotrophic factor-like intracellular signals to protect or ameliorate neurological/psychiatric diseases. 2-Decenoic acid derivatives and other similar molecules could protect or ameliorate in animal models of mood disorders such as depression and enhance recovery from spinal cord injury-induced motor paralysis. Compounds that can generate neurotrophin-like signals in neurons are expected to be developed as therapeutic drugs for certain neurological or psychiatric disorders.