The neuroprotective agent memantine induces brain-derived neurotrophic factor and trkB receptor expression in rat brain

被引：142

作者：

Marvanová, M

Lakso, M

Pirhonen, J

Nawa, H

Wong, G

Castrén, E

机构：

[1] Univ Kuopio, AI Virtanen Inst, FIN-70211 Kuopio, Finland

[2] Univ Kuopio, Dept Psychiat, FIN-70211 Kuopio, Finland

[3] Ctr Comp Sci, Espoo 02101, Finland

[4] Niigata Univ, Brain Res Inst, Dept Mol Biol & Neurobiol, Niigata 9518585, Japan

来源：

MOLECULAR AND CELLULAR NEUROSCIENCE | 2001年 / 18卷 / 03期

基金：

芬兰科学院;

关键词：

D O I：

10.1006/mcne.2001.1027

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Memantine is a medium-affinity uncompetitive N-methyl-D-aspartate receptor antagonist and has been clinically used as a neuroprotective agent to treat Alzheimer's and Parkinson's diseases. We have examined the effect of memantine (ip 5-50 mg/kg; 4 h) on the expression of brain-derived neurotrophic factor (BDNF) and trkB receptor mRNAs in rat brain by in situ hybridization. Memantine at a clinically relevant dose markedly increased BDNF mRNA levels in the limbic cortex, and this effect was more widespread and pronounced at higher doses. Effects of memantine on BDNF mRNA were also reflected in changes in BDNF protein levels. Moreover, memantine induced isoforms of the BDNF receptor trkB. Taken together, these data suggest that the neuroprotective properties of memantine could be mediated by the increased endogenous production of BDNF in the brain. These findings may open up new possibilities of pharmacologically regulating the expression of neurotrophic factors in the brain.

引用

页码：247 / 258

页数：12

共 73 条

[41] Expression of a dominant negative TrkB receptor, T1, reveals a requirement for presynaptic signaling in BDNF-induced synaptic potentiation in cultured hippocampal neurons [J].