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 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.
Nitta
A
A
Laboratory of Molecular Biology, Gifu Pharmaceutical University, Mitahora-higashi, Japan.
Ito
M
M
Fukumitsu
H
H
Ohmiya
M
M
Ito
H
H
Sometani
A
A
Nomoto
H
H
Furukawa
Y
Y
Furukawa
S
S
D000818:Animals; D000831:Animals, Newborn; D001923:Brain Chemistry / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000378:metabolism*; D002396:Catechols / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
D019208:Brain-Derived Neurotrophic Factor; D002396:Catechols; D018696:Neuroprotective Agents; D012333:RNA, Messenger; C018599:4-methylcatechol