PT  - JOURNAL ARTICLE
AU  - Atsumi Nitta
AU  - Megumi Ito
AU  - Hidefumi Fukumitsu
AU  - Makoto Ohmiya
AU  - Hisanori Ito
AU  - Ayako Sometani
AU  - Hiroshi Nomoto
AU  - Yoshiko Furukawa
AU  - Shoei Furukawa
TI  - 4-Methylcatechol Increases Brain-Derived Neurotrophic Factor Content and mRNA Expression in Cultured Brain Cells and in Rat Brain In Vivo
DP  - 1999 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1276--1283
VI  - 291
IP  - 3
4099  - http://jpet.aspetjournals.org/content/291/3/1276.short
4100  - http://jpet.aspetjournals.org/content/291/3/1276.full
SO  - J Pharmacol Exp Ther1999 Dec 01; 291
AB  - Practical use of brain-derived neurotrophic factor (BDNF) as therapy is limited by two serious problems, i.e., its inability to cross the blood-brain barrier and its instability in the bloodstream. In the present study, we investigated the effects of 4-methylcatechol (4-MC), which stimulates nerve growth factor synthesis and protects against peripheral neuropathies in rats, on BDNF content and mRNA expression in cultured brain cells and in vivo in the rat brain. 4-MC elevated BDNF content in culture media of both rat astrocytes and neurons with different dose-response relations. The increase in BDNF mRNA level was correlated with the increase in BDNF content, demonstrating that 4-MC can stimulate BDNF synthesis of both neurons and astrocytes. Then we examined the in vivo effects of 4-MC. First, we found that ventricularly administered 4-MC facilitated an increase in the BDNF content in the cerebral cortex and hippocampus in association with its diffusion into the brain parenchyma. Second, i.p. administration of 4-MC enhanced BDNF mRNA expression in the infant rat brain, in which the blood-brain has not yet fully been established. These results demonstrate that 4-MC, once delivered into the brain, can stimulate BDNF synthesis. The American Society for Pharmacology and Experimental Therapeutics