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.
Footnotes
-
Send reprint requests to: Shoei Furukawa, Ph.D., Laboratory of Molecular Biology, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan. E-mail: furukawa{at}gifu-pu.ac.jp
-
↵1 This work is supported, in part, by Health Science Research Grant (Research on Brain Science) from the Ministry of Health and Welfare and by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan.
- Abbreviations:
- BDNF
- brain-derived neurotrophic factor
- NGF
- nerve growth factor
- NT
- neurotrophin
- CNS
- central nervous system
- BBB
- blood-brain barrier
- 4-MC
- 4-methylcatechol
- DMEM
- Dulbecco's modified Eagle's medium
- FCS
- fetal calf serum
- RT-PCR
- reverse transcription-polymerase chain reaction
- CM
- conditioned medium
- EIA
- enzyme immunoassay
- GDNF
- glial cell line-derived neurotrophic factor
- PFA
- paraformaldehyde
- Received May 20, 1999.
- Accepted August 24, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|