Brain-derived neurotrophic factor rescues neuronal death induced by methamphetamine
Received 5 March 2003; received in revised form 23 June 2003; accepted 16 July 2003.
Abstract
Background
Methamphetamine (MA) induces degeneration of various regions of the brain, resulting in neuropsychiatric damage. Although the underlying mechanisms of MA-induced neurotoxicity have been studied, there are few reports to date regarding the factor(s) that can effectively prevent MA-induced neurotoxicity. Because brain-derived neurotrophic factor (BDNF) has been known to prevent many kinds of neuronal cell death, we investigated whether BDNF inhibits MA-induced neuronal death.
Methods
Using primary cortical neurons, we examined the effect of BDNF on MA-induced neuronal death. In addition, using pharmacologic and molecular biological tools, we elucidated which pathways are involved in this effect.
Results
Brain-derived neurotrophic factor dose-dependently blocked MA-induced neuronal death, and this effect was inhibited by phosphatidylinositol-3-kinase inhibitors. In addition, overexpression of activated Akt protects neurons against MA. Furthermore, expression of kinase-defective Akt blocked the effect of BDNF on MA-induced neuronal death.
Conclusions
Brain-derived neurotrophic factor effectively blocks MA-induced neuronal death, and Akt activation is necessary and sufficient for this effect.
aDepartment of Anatomy and Neuroscience (HM, KS), Hamamatsu University School of Medicine, Shizuoka, Japan
bDepartment of Psychiatry and Neurology (NM), Hamamatsu University School of Medicine, Shizuoka, Japan
cDepartment of Anatomy (KN, HK), Osaka City University, Osaka, Japan
Address reprint requests to Kohji Sato, M.D., Ph.D., Hamamatsu University School of Medicine, Department of Anatomy and Neuroscience, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan.
ABSTRACT