Attenuation of N-methyl-D-aspartate-mediated cytoplasmic vacuolization in primary rat hippocampal neurons by mood stabilizers.
Recent post-mortem and brain imaging studies suggest that decreased neuronal and glial densities may account for cell loss in vulnerable brain regions such as the hippocampus and the frontal cortex in patients with bipolar disorder. Investigations into the mechanisms of action of mood stabilizers suggest that these drugs may regulate the expression of neuroprotective genes and protect against excitotoxicity. In this study, we characterized the ultrastructural appearance of rat hippocampal neurons pretreated with mood stabilizers and then exposed to the glutamate receptor agonist N-methyl-D-aspartate. Using transmission electron microscopy we found that rat hippocampal neurons exposed to 0.5 mM N-methyl-D-aspartate for 10 min produced more cytoplasmic vacuolization than in control neurons. Chronic treatment with mood stabilizers, lithium, valproate or carbamazepine for 7 days at therapeutically relevant concentrations fully attenuated N-methyl-D-aspartate-mediated cytoplasmic vacuolization. These results suggest that inhibition of neurotoxicity may be involved in the action of mood stabilizers.
Bown
C D
CD
Mood Disorders Program, Department of Psychiatry, 1200 Main Street West, McMaster University, L8N 3Z5, Hamilton, Ontario, Canada.
Wang
J F
JF
Young
L T
LT
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002220:Carbamazepine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003593:Cytoplasm / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D004347:Drug Interactions / Q000502:physiology; D005333:Fetus; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008094:Lithium / Q000494:pharmacology; D008854:Microscopy, Electron; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D016896:Treatment Outcome; D014617:Vacuoles / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D014635:Valproic Acid / Q000494:pharmacology
D018692:Antimanic Agents; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D002220:Carbamazepine; D014635:Valproic Acid; D016202:N-Methylaspartate; D008094:Lithium; D010751:Phosphopyruvate Hydratase