Alterations in dopamine and glutamate neurotransmission in tetrahydrobiopterin deficient spr-/- mice: relevance to schizophrenia.
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.
Choi
Yong Kee
YK
Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, USA. ykchoi@mclean.harvard.edu
Tarazi
Frank I
FI
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*
D001708:Biopterins; D018698:Glutamic Acid; D000429:Alcohol Oxidoreductases; C022630:sepiapterin reductase; C003402:sapropterin; D004298:Dopamine