PMID- 10565852 OWN - NLM STAT- MEDLINE DCOM- 19991220 LR - 20151119 IS - 0022-3565 (Print) IS - 0022-3565 (Linking) VI - 291 IP - 3 DP - 1999 Dec TI - 4-methylcatechol increases brain-derived neurotrophic factor content and mRNA expression in cultured brain cells and in rat brain in vivo. PG - 1276-83 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. FAU - Nitta, A AU - Nitta A AD - Laboratory of Molecular Biology, Gifu Pharmaceutical University, Mitahora-higashi, Japan. FAU - Ito, M AU - Ito M FAU - Fukumitsu, H AU - Fukumitsu H FAU - Ohmiya, M AU - Ohmiya M FAU - Ito, H AU - Ito H FAU - Sometani, A AU - Sometani A FAU - Nomoto, H AU - Nomoto H FAU - Furukawa, Y AU - Furukawa Y FAU - Furukawa, S AU - Furukawa S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Pharmacol Exp Ther JT - The Journal of pharmacology and experimental therapeutics JID - 0376362 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Catechols) RN - 0 (Neuroprotective Agents) RN - 0 (RNA, Messenger) RN - 12GLI7JGB3 (4-methylcatechol) SB - IM MH - Animals MH - Animals, Newborn MH - Brain Chemistry/*drug effects MH - Brain-Derived Neurotrophic Factor/biosynthesis/*metabolism MH - Catechols/administration & dosage/*pharmacology MH - Cells, Cultured MH - Hippocampus/cytology/drug effects/metabolism MH - Injections, Intravenous MH - Injections, Intraventricular MH - Male MH - Neuroprotective Agents/administration & dosage/*pharmacology MH - RNA, Messenger/*biosynthesis MH - Rats MH - Rats, Wistar MH - Stimulation, Chemical EDAT- 1999/11/24 00:00 MHDA- 1999/11/24 00:01 CRDT- 1999/11/24 00:00 PHST- 1999/11/24 00:00 [pubmed] PHST- 1999/11/24 00:01 [medline] PHST- 1999/11/24 00:00 [entrez] PST - ppublish SO - J Pharmacol Exp Ther. 1999 Dec;291(3):1276-83.