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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1276-1283
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume291
Issue number3
DOIs
StatePublished - 1999/12

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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