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: Yong Kee Choi, Frank I Tarazi
• Journal: BMB reports (BMB Rep) Vol. 43 Issue 9 Pg. 593-8 (Sep 2010) ISSN: 1976-670X [Electronic] Korea (South)
• PMID: 20846490 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Biopterin
• Glutamic Acid
• Alcohol Oxidoreductases
• sepiapterin reductase
• sapropterin
• Dopamine

Topics

• Alcohol Oxidoreductases (genetics, metabolism)
• Animals
• Biopterin (analogs & derivatives, genetics, metabolism)
• Dopamine (metabolism)
• Glutamic Acid (metabolism)
• Humans
• Mice
• Models, Biological
• Schizophrenia (genetics, metabolism)
• Synaptic Transmission (genetics, physiology)