Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons.
Agmatine is a polyamine and has been considered as a novel neurotransmitter or neuromodulator in the central nervous system. In the present study, the neuroprotective effect of agmatine against cell damage caused by N-methyl-D-aspartate (NMDA) and glutamate was investigated in cultured rat hippocampal neurons. Lactate dehydrogenase (LDH) activity assay, beta-tubulin III immunocytochemical staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end-labeling (TUNEL) assay were conducted to detect cell damage. Exposure of 12-day neuronal cultures of rat hippocampus to NMDA or glutamate for 1 h caused a concentration-dependent neurotoxicity, as indicated by the significant increase in released LDH activities. Addition of 100 microM agmatine into media ablated the neurotoxicity induced by NMDA or glutamate, an effect also produced by the specific NMDA receptor antagonist dizocilpine hydrogen maleate (MK801). Arcaine, an analog of agmatine with similar structure as agmatine, fully prevented the NMDA- or glutamate-induced neuronal damage. Spermine and putrescine, the endogenous polyamine and metabolic products of agmatine without the guanidine moiety of agmatine, failed to show this effect, indicating a structural relevance for this neuroprotection. Immunocytochemical staining and TUNEL assay confirmed the findings in the LDH measurement. That is, agmatine and MK801 markedly attenuated NMDA-induced neuronal death and significantly reduced TUNEL-positive cell numbers induced by exposure of cultured hippocampal neurons to NMDA. Taken together, these results demonstrate that agmatine can protect cultured hippocampal neurons from NMDA- or glutamate-induced excitotoxicity, through a possible blockade of the NMDA receptor channels or a potential anti-apoptotic property.
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216, USA.
Wei-Ping
WP
Wang
Abiye H
AH
Iyo
Javier
J
Miguel-Hidalgo
Soundar
S
Regunathan
Meng-Yang
MY
Zhu
D000376:Agmatine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D014404:Tubulin / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D014404:Tubulin; D004281:Docosahexaenoic Acids; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D000376:Agmatine; D007770:L-Lactate Dehydrogenase