4-methylcatechol increases brain-derived neurotrophic factor content and mRNA expression in cultured brain cells and in rat brain in vivo

Practical use of brain-derived neurotrophic factor (BDNF) as therapy is lim ited 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 in vestigated the effects of 4-methylcatechol (4-MC), which stimulates nerve g rowth factor synthesis and protects against peripheral neuropathies in rats , on BDNF content and mRNA expression in cultured brain cells and in vivo i n the rat brain. 4-MC elevated BDNF content in culture media of both rat as trocytes and neurons with different dose-response relations. The increase i n BDNF mRNA level was correlated with the increase in BDNF content, demonst rating that 4-MC can stimulate BDNF synthesis of both neurons and astrocyte s. Then we examined the in vivo effects of 4-MC. First, we found that ventr icularly administered 4-MC facilitated an increase in the BDNF content in t he cerebral cortex and hippocampus in association with its diffusion into t he 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 f ully been established. These results demonstrate that 4-MC, once delivered into the brain, can stimulate BDNF synthesis.