title: Alterations in dopamine and glutamate neurotransmission in tetrahydrobiopterin deficient spr-/- mice: relevance to schizophrenia.
abstract: Tetrahydrobiopterin (BH4) is a pivotal cofactor for enzymes responsible for the synthesis and release of monoamine neurotransmitters including dopamine (DA) and serotonin (5-HT) as well as the release of glutamate (Glu). Deficiencies in BH4 levels and reduced activities of BH(4)-associated enzymes have been recently reported in patients with schizophrenia. Accordingly, it is possible that abnormalities in the biochemical cascades regulated by BH(4) may alter DA, 5-HT and Glu neurotransmission, and consequently contribute to the pathophysiology of different neuropsychiatric diseases including schizophrenia. The development of a novel strain of mutant mice that is deficient in BH(4) by knocking out the expression of a functional sepiapterin reductase gene (spr -/-) has added new insights into the potential role of BH(4) in the pathophysiology and improved treatment of schizophrenia.
authors.affiliation: Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, USA. ykchoi@mclean.harvard.edu
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Choi
authors.forename: Frank I
authors.initials: FI
authors.lastname: Tarazi
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*
chemical_list: D001708:Biopterins; D018698:Glutamic Acid; D000429:Alcohol Oxidoreductases; C022630:sepiapterin reductase; C003402:sapropterin; D004298:Dopamine