POSTER

Dmitri

Tkachev^1,3, Michael L. Mimmack^1,3, Margaret M. Ryan^1,3,

Matt Wayland², Tom Freeman², Maree J. Webster⁴,

1Department of

Neurobiology, Babraham Institute, Cambridge CB2 4AT, UK; ²UK Human

Genome Mapping Project Resource Centre, Hinxton, Cambridge CB10 1SB, UK; ³Department

of Psychiatry, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2

2QQ, UK; ⁴Stanley Laboratory of Brain Research, Department of

Psychiatry, Uniformed Services University for the Health Sciences, 4301 Jones

Bridge Road, 20814-4709, Bethesda, MD, USA; ⁵Stanley Division of

Developmental Neurovirology, Johns Hopkins School of Medicine, Baltimore, MD

BACKGROUND:  The glutamate hypothesis of schizophrenia has been one of the

prominent theories for many years.  Other evidence also suggests a GABAergic

dysfunction in schizophrenia.  To add to the puzzle, several independent gene

expression-profiling studies have recently found abnormalities in the expression

of myelin- and oligodendrocyte-specific genes. Here we provide evidence from

post-mortem brain studies that suggest abnormalities in the metabolism of

several amino acids, which are closely linked to myelination, Glutamatergic and

GABAergic neurotransmission based on parallel metabolic and transcriptomics

METHODS: 

HPLC methods were employed to measure and compare the concentrations of NAA,

Glu, Asp, Arg, Gly, Cit, Tau, and GABA. Microarrays and Q-PCR were used to

examine expression levels of enzymes associated with the metabolites that showed

RESULTS: 

We have identified differences for the following metabolites: NAA, Asp, and Arg

were up-regulated, GABA was down-regulated.  Microarray and quantitative PCR

revealed abnormalities at the mRNA level for several key enzymes involved in the

CONCLUSIONS:  Our results suggest multiple abnormalities in the amino acid

metabolism in schizophrenia resulting in changes in metabolite concentrations. 

This was associated with the transcriptional dysregulations of key enzymes