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Further evidence for altered myelin biosynthesis and glutamatergic dysfunction in schizophrenia

  • Dmitri Tkachev (a1) (a2), Michael L. Mimmack (a1), Stephen J. Huffaker (a1), Margaret Ryan (a1) and Sabine Bahn (a1)...
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.

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Corresponding author
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
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The International Journal of Neuropsychopharmacology
  • ISSN: 1461-1457
  • EISSN: 1469-5111
  • URL: /core/journals/the-international-journal-of-neuropsychopharmacology
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