The International Journal of Neuropsychopharmacology



Special Section

Further evidence for altered myelin biosynthesis and glutamatergic dysfunction in schizophrenia


Dmitri Tkachev a1a2 1 , Michael L. Mimmack a1 1 , Stephen J. Huffaker a1, Margaret Ryan a1 and Sabine Bahn a1c1
a1 Institute of Biotechnology, Tennis Court Road, Cambridge, UK
a2 Department of Neurobiology, Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, Im Neuenheimer Feld, Heidelberg, Germany

Article author query
tkachev d   [PubMed][Google Scholar] 
mimmack ml   [PubMed][Google Scholar] 
huffaker sj   [PubMed][Google Scholar] 
ryan m   [PubMed][Google Scholar] 
bahn s   [PubMed][Google Scholar] 

Abstract

Recent studies have provided evidence for neuronal and oligodendrocyte-related abnormalities being associated with schizophrenia. However, the functional interplay and causal relationship between these two abnormalities is poorly understood. In this report, we provide data that identify myelin and fatty-acid biosynthesis dysfunction in schizophrenia based on post-mortem brain studies (prefrontal cortex) utilizing parallel metabolic and transcriptomics investigations. We detected a significant up-regulation of N-acetylaspartate (NAA) by HPLC analysis. Microarray and Q-PCR investigations revealed mRNA abnormalities for several enzymes involved in NAA metabolism. Additionally, glutamatergic neurotransmission components were also found to be affected. Our results suggest that, apart from the previously reported alterations in myelin-related protein synthesis, myelin synthesis itself may be directly affected in schizophrenia as indicated by changes in key enzymes involved in NAA metabolism. A decrease in NAA catabolism in oligodendrocytes would severely reduce acetate levels required to produce myelin lipids and may subsequently affect glutamatergic neurotransmission.

(Received July 5 2006)
(Reviewed August 7 2006)
(Revised August 29 2006)
(Accepted September 3 2006)


Key Words: Acetate; glutamate; lipids; myelination; NAA.

Correspondence:
c1 Cambridge Centre for Neuropsychiatric Research, Institute of Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QT, UK. Tel.: +44 (0) 1223 767799 Fax: +44 (0) 1223 334162 E-mail: sb209@cam.ac.uk


Footnotes

1 These authors contributed equally to this work.



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