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 and serotonin as well as the release of glutamate. Deficiencies in BH₄ levels and reduced activities of BH₄-associated enzymes have been recently reported in patients with schizophrenia. Accordingly, it is possible that abnormalities in the biochemical cascades regulated by BH₄ 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 BH₄ by knocking out the expression of a functional sepiapterin reductase gene (spr-/-) has added new insights into the potential role of BH₄ in the pathophysiology and improved treatment of schizophrenia.