AIMTo observe the impairment of homocysteine (Hcy) on neurons in vitro and the related mechanisms.

METHODSWe examined the consequences of treatment of cultured rat cortical and hippocampal neurons with Hcy and detected the neurons' apoptosis, calcium influx, DNA damage and oxidative injury.

RESULTSPrimary cortical and hippocampal neurons were treated with Hcy (250 micromol/L) for 4 h resulted in apoptosis time-dependently. S-adenosyl methionine (SAM) could significantly, but MK-801, an NMDA receptor inhibitor, couldn't repress the Hcy induced neuron apoptosis. Hcy could induce neuron calcium overload through activating the NMDA receptors. The DNA of neurons was damaged by Hcy because the methylation reactions were inhibited. Hcy treatment also induced MDA level significantly increased, but did not affect the neurons' T-AOC.

CONCLUSIONThese findings indicate that Hcy compromises neuronal homeostasis by multiple, divergent routes, including DNA damage, neuron exitotoxicity, and oxidative injury. Hcy mediated neuron apoptosis was mainly due to DNA damage.

Animals ; Apoptosis ; Calcium ; metabolism ; DNA Damage ; Hippocampus ; drug effects ; pathology ; Homocysteine ; metabolism ; pharmacology ; Neurons ; drug effects ; metabolism ; Oxidative Stress ; Rats ; Rats, Wistar