TY - JOUR
T1 - 4-Methylcatechol increases brain-derived neurotrophic factor content and mRNA expression in cultured brain cells and in rat brain in vivo
AU - Nitta, Atsumi
AU - Ito, Megumi
AU - Fukumitsu, Hidefumi
AU - Ohmiya, Makoto
AU - Ito, Hisanori
AU - Sometani, Ayako
AU - Nomoto, Hiroshi
AU - Furukawa, Yoshiko
AU - Furukawa, Shoei
PY - 1999/12
Y1 - 1999/12
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=0032732617&partnerID=8YFLogxK
U2 - 10.1016/s0022-3565(24)35237-1
DO - 10.1016/s0022-3565(24)35237-1
M3 - 学術論文
C2 - 10565852
AN - SCOPUS:0032732617
SN - 0022-3565
VL - 291
SP - 1276
EP - 1283
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 3
ER -