Altered Vesicular Glutamate Transporter Expression in the Anterior Cingulate Cortex in Schizophrenia
| Autor: | Vahram Haroutunian, James H. Meador-Woodruff, Akin Oni-Orisan, Lars V. Kristiansen, Robert E. McCullumsmith |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Cingulate cortex medicine.medical_specialty Psychosis Transcription Genetic Synaptic cleft Blotting Western Gene Expression Prefrontal Cortex Neurotransmission Biology Vesicular Glutamate Transport Protein 2 Gyrus Cinguli behavioral disciplines and activities Article Rats Sprague-Dawley Reference Values Internal medicine mental disorders medicine Animals Humans RNA Messenger Dominance Cerebral In Situ Hybridization Biological Psychiatry Anterior cingulate cortex Aged Aged 80 and over Glutamate receptor medicine.disease Rats Dorsolateral prefrontal cortex Endocrinology medicine.anatomical_structure Vesicular Glutamate Transport Protein 1 Schizophrenia Haloperidol Female Neuroscience Antipsychotic Agents |
| Zdroj: | Biological Psychiatry. 63:766-775 |
| ISSN: | 0006-3223 |
| DOI: | 10.1016/j.biopsych.2007.10.020 |
| Popis: | Background Schizophrenia is a chronic, severe mental illness with profound emotional and economic burdens for those afflicted and their families. An increasing number of studies have found that schizophrenia is marked by dysregulation of glutamatergic neurotransmission. While numerous studies have found alterations of postsynaptic molecules in schizophrenia, a growing body of evidence implicates presynaptic factors. Vesicular glutamate transporters (VGLUTs) have been identified and are known to package glutamate into vesicles in the presynaptic terminal for subsequent release into the synaptic cleft. Recent studies have shown that VGLUTs regulate synaptic activity via the amount of glutamate released. Accordingly, we hypothesized that VGLUTs are altered in schizophrenia, contributing to dysfunction of presynaptic activity. Methods Using in situ hybridization and Western blot analysis, we investigated alterations in VGLUT1 and VGLUT2 transcript and protein expression in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia and a comparison group. Results We found increased VGLUT1 transcript and reduced VGLUT1 protein expression in the ACC, but not DLPFC, in schizophrenia. Vesicular glutamate transporter 2 was unchanged at both levels of gene expression. We did not find changes in VGLUT1 messenger RNA (mRNA) or protein levels following 28-day treatment of rats with haloperidol (2 mg/kg/day), suggesting that our findings in schizophrenia are not due to an effect of antipsychotic treatment. Conclusions Overall, our data suggest decreased glutamate release in the ACC, as well as discordant regulation of VGLUT1 expression at different levels of gene expression. |
| Databáze: | OpenAIRE |
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