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. 2008 Sep;104(1-3):108-20.
doi: 10.1016/j.schres.2008.06.012. Epub 2008 Aug 3.

Abnormal expression of glutamate transporter and transporter interacting molecules in prefrontal cortex in elderly patients with schizophrenia

Deborah Bauer  1 , Daya Gupta, Vahram Harotunian, James H Meador-Woodruff, Robert E McCullumsmith
Affiliations

Abnormal expression of glutamate transporter and transporter interacting molecules in prefrontal cortex in elderly patients with schizophrenia

Deborah Bauer et al. Schizophr Res. 2008 Sep.

Abstract

Glutamate cycling is critically important for neurotransmission, and may be altered in schizophrenia. The excitatory amino acid transporters (EAATs) facilitate the reuptake of glutamate from the synaptic cleft and have a key role in glutamate cycling. We hypothesized that expression of the EAATs and the EAAT regulating proteins ARHGEF11, JWA, G-protein suppressor pathway 1 (GPS1), and KIAA0302 are altered in the brain in schizophrenia. To test this, we measured expression of EAAT1, EAAT2, EAAT3, and EAAT interacting proteins in postmortem tissue from the dorsolateral prefrontal and anterior cingulate cortex of patients with schizophrenia and a comparison group using in situ hybridization and Western blot analysis. We found increased EAAT1 transcripts and decreased protein expression, increased EAAT3 transcripts and protein, and elevated protein expression of both GPS1 and KIAA0302 protein. We did not find any changes in expression of EAAT2. These data indicate that proteins involved in glutamate reuptake and cycling are altered in the cortex in schizophrenia, and may provide potential _targets for future treatment strategies.

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Figures

Figure 1
Figure 1. EAAT transcript expression
In situ hybridization analysis of EAAT1-3 mRNA expression in the anterior cingulate cortex and dorsolateral prefrontal cortex from control and schizophrenia subjects. Nissl stained sections are shown for comparison. Roman numerals indicate cortical layers. Data expressed as means +/− standard error of the mean. Asterisks indicate a significant difference between control and schizophrenia (p < 0.05). Abbreviations: Optical density (OD), control (C), schizophrenia (S), anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), excitatory amino acid transporter (EAAT), layer I (I), white matter (WM).
Figure 2
Figure 2. EAAT interacting partner transcript expression
In situ hybridization analysis of ARHGEF11, GPS1, JWA, and KIAA0302 mRNA expression in the anterior cingulate cortex and dorsolateral prefrontal cortex from control and schizophrenia subjects. Data expressed as means +/− standard error of the mean. Abbreviations: Optical density (OD), control (C), schizophrenia (S), anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), ARHGEF11 (ARH), G-protein suppressor pathway 1 (GPS1), KIAA0302 (KIAA), layer I (I), white matter (WM).
Figure 3
Figure 3. Probe specificity of KIAA0302 and GPS1
In situ hybridization analysis of KIAA0302 and GPS1 mRNA expression using sense and antisense probes in anterior cingulate cortex. Abbreviations: KIAA0302 (KIAA).
Figure 4
Figure 4. Cellular expression pattern of EAAT2
Emulsion dipped in situ hybridization of EAAT2 mRNA in nissl stained tissue from the vicinity of layer V of anterior cingulate cortex. Large circle indicates large cell, small circles indicate small cells.
Figure 5
Figure 5. Protein expression profiles
Western blot analysis of all proteins studied. Numbers on left indicate molecular weight in kDa. Abbreviations: KIAA0302 (KIAA).
Figure 6
Figure 6. EAAT and EAAT interacting partner protein expression
Western blot analysis in the anterior cingulate cortex and dorsolateral prefrontal cortex from control and schizophrenia subjects for EAAT1–3, GPS1, and KIAA0302. Values are normalized to tubulin. Asterisks indicate a significant difference between control and schizophrenia (p < 0.05). Data expressed as means +/− standard error of the mean. Abbreviations: Optical density (OD), control (CTL), schizophrenia (SCZ), anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), excitatory amino acid transporter (EAAT).
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