Transforming growth factor-beta2 increases NMDA receptor-mediated excitotoxicity in rat cerebral cortical neurons independently of glia.
The ability of transforming growth factor-beta2 (TGFbeta2) to directly regulate neuronal sensitivity to glutamate and N-methyl-D-aspartate (NMDA) excitotoxicity in rat cerebral cortical neurons was investigated. Mixed neuronal-glial cultures treated with TGFbeta2 (1-10 ng/ml) exhibited a significant 25-50% increase in neuronal death compared to control cultures. TGFbeta2 potentiation of this endogenous glutamate excitotoxicity was blocked by the selective NMDA receptor antagonist, 2-amino-5-phosphonovalerate. In addition, neuronal death induced by brief NMDA exposure in both mixed neuronal-glial and pure neuronal cultures was increased by TGFbeta2 (1-30 ng/ml) with a similar dose-response curve. These findings indicate that TGFbeta2, at physiologically relevant concentrations, potentiates NMDA receptor-mediated excitotoxicity and that this occurs independently of TGFbeta2 effects on glia.
Kane
C J
CJ
Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205, USA.cjkane@comdean2.uams.edu
Brown
G J
GJ
Phelan
K D
KD
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000502:physiology*; D005260:Female; D016202:N-Methylaspartate / Q000633:toxicity*; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D016212:Transforming Growth Factor beta; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate