title: Antipsychotic drugs increase N-acetylaspartate and N-acetylaspartylglutamate in SH-SY5Y human neuroblastoma cells.
abstract: N-Acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) are related neuronal metabolites associated with the diagnosis and treatment of schizophrenia. NAA is a valuable marker of neuronal viability in magnetic resonance spectroscopy, a technique which has consistently shown NAA levels to be modestly decreased in the brains of schizophrenia patients. However, there are conflicting reports on the changes in brain NAA levels after treatment with antipsychotic drugs, which exert their therapeutic effects in part by blocking dopamine D(2) receptors. NAAG is reported to be an agonist of the metabotropic glutamate 2/3 receptor, which is linked to neurotransmitter release modulation, including glutamate release. Alterations in NAAG metabolism have been implicated in the development of schizophrenia possibly via dysregulation of glutamate neurotransmission. In the present study we have used high performance liquid chromatography to determine the effects of the antipsychotic drugs haloperidol and clozapine on NAA and NAAG levels in SH-SY5Y human neuroblastoma cells, a model system used to test the responses of dopaminergic neurons in vitro. The results indicate that the antipsychotic drugs haloperidol and clozapine increase both NAA and NAAG levels in SH-SY5Y cells in a dose and time dependant manner, providing evidence that NAA and NAAG metabolism in neurons is responsive to antipsychotic drug treatment.
authors.affiliation: Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
authors.forename: Peethambaran
authors.initials: P
authors.lastname: Arun
authors.forename: Chikkathur N
authors.initials: CN
authors.lastname: Madhavarao
authors.forename: John R
authors.initials: JR
authors.lastname: Moffett
authors.forename: Aryan M A
authors.initials: AM
authors.lastname: Namboodiri
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D003024:Clozapine / Q000494:pharmacology; D004151:Dipeptides / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D004151:Dipeptides; C027172:isospaglumic acid; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003024:Clozapine; D006220:Haloperidol