The role of NMDA and mGluR5 receptors in calcium mobilization and neurotoxicity of homocysteine in trigeminal and cortical neurons and glial cells

摘要: Recent studies suggested contribution of homocysteine (HCY) to neurodegenerative disorders and migraine. However, HCY effect in the nociceptive system is essentially unknown. To explore mechanism action, we studied short- long-term effects this amino acid on rat peripheral central neurons. induced intracellular Ca2+ transients cultured trigeminal neurons satellite glial cells (SGC), which were blocked by NMDA antagonist AP-5 neurons, but not SGCs. In contrast, 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP), metabotropic mGluR5 (metabotropic glutamate receptor 5 subtype) antagonist, preferentially inhibited Prolonged application apoptotic cell death both kinds cells. The apoptosis was or MTEP. Likewise, cortical HCY-induced Imaging with 2′,7′-dichlorodihydrofluorescein diacetate mitochondrial dye Rhodamine-123 as well thiobarbituric reactive substances assay did reveal involvement oxidative stress action HCY. Thus, elevation mediated receptors while SGC are activated through subtype. Long-term neurotoxic involved types. Our data suggest glutamatergic mechanisms sensitization nociceptors. We show that mediate (HCY)-induced [Ca2+]i whereas HCY-evoked involves receptors. This study revealed migraine-related redox active aminoacid within highlights potential targets for anti-nociception neuroprotection.