Vol. 291, Issue 3, 1276-1283, December 1999

4-Methylcatechol Increases Brain-Derived Neurotrophic Factor Content and mRNA Expression in Cultured Brain Cells and in Rat Brain In Vivo¹

Atsumi Nitta, Megumi Ito, Hidefumi Fukumitsu, Makoto Ohmiya, Hisanori Ito, Ayako Sometani, Hiroshi Nomoto, Yoshiko Furukawa and Shoei Furukawa

Laboratory of Molecular Biology, Gifu Pharmaceutical University, Mitahora-higashi, Japan (A.N., M.I., H.F., M.O., H.I., A.S., H.N., S.F.); and Aichi Bunkyo Women's College, Nishi-Machi, Inazawa, Japan (Y.F.)

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.