Abstract | 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: 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.
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Authors | Akin Oni-Orisan, Lars V Kristiansen, Vahram Haroutunian, James H Meador-Woodruff, Robert E McCullumsmith |
Journal | Biological psychiatry
(Biol Psychiatry)
Vol. 63
Issue 8
Pg. 766-75
(Apr 15 2008)
ISSN: 1873-2402 [Electronic] United States |
PMID | 18155679
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Antipsychotic Agents
- RNA, Messenger
- SLC17A6 protein, human
- SLC17A7 protein, human
- Vesicular Glutamate Transport Protein 1
- Vesicular Glutamate Transport Protein 2
- Haloperidol
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Topics |
- Aged
- Aged, 80 and over
- Animals
- Antipsychotic Agents
(pharmacology)
- Blotting, Western
- Dominance, Cerebral
(physiology)
- Female
- Gene Expression
(genetics)
- Gyrus Cinguli
(drug effects, pathology)
- Haloperidol
(pharmacology)
- Humans
- In Situ Hybridization
- Male
- Prefrontal Cortex
(drug effects, pathology)
- RNA, Messenger
(genetics)
- Rats
- Rats, Sprague-Dawley
- Reference Values
- Schizophrenia
(genetics, pathology)
- Transcription, Genetic
(drug effects, genetics)
- Vesicular Glutamate Transport Protein 1
(genetics)
- Vesicular Glutamate Transport Protein 2
(genetics)
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