Dataset Information

Enzymes in the glutamate-glutamine cycle in the anterior cingulate cortex in postmortem brain of subjects with autism.

ABSTRACT:

Background

Accumulating evidence suggests that dysfunction in the glutamatergic system may underlie the pathophysiology of autism. The anterior cingulate cortex (ACC) has been implicated in autism as well as in glutamatergic neurotransmission. We hypothesized that alterations in the glutamate-glutamine cycle in the ACC might play a role in the pathophysiology of autism.

Methods

We performed Western blot analyses for the protein expression levels of enzymes in the glutamate-glutamine cycle, including glutamine synthetase, kidney-type glutaminase, liver-type glutaminase, and glutamate dehydrogenases 1 and 2, in the ACC of postmortem brain of individuals with autism (n?=?7) and control subjects (n?=?13).

Results

We found that the protein levels of kidney-type glutaminase, but not those of the other enzymes measured, in the ACC were significantly lower in subjects with autism than in controls.

Conclusion

The results suggest that reduced expression of kidney-type glutaminase may account for putative alterations in glutamatergic neurotransmission in the ACC in autism.

SUBMITTER: Shimmura C

PROVIDER: S-EPMC3621600 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Publications

Enzymes in the glutamate-glutamine cycle in the anterior cingulate cortex in postmortem brain of subjects with autism.

Shimmura Chie C Suzuki Katsuaki K Iwata Yasuhide Y Tsuchiya Kenji J KJ Ohno Koji K Matsuzaki Hideo H Iwata Keiko K Kameno Yosuke Y Takahashi Taro T Wakuda Tomoyasu T Nakamura Kazuhiko K Hashimoto Kenji K Mori Norio N

Molecular autism 20130326 1

<h4>Background</h4>Accumulating evidence suggests that dysfunction in the glutamatergic system may underlie the pathophysiology of autism. The anterior cingulate cortex (ACC) has been implicated in autism as well as in glutamatergic neurotransmission. We hypothesized that alterations in the glutamate-glutamine cycle in the ACC might play a role in the pathophysiology of autism.<h4>Methods</h4>We performed Western blot analyses for the protein expression levels of enzymes in the glutamate-glutami ...[more]

PMID: 23531457

Similar Datasets

Project description:Human connectome studies have provided abundant data consistent with the hypothesis that functional dysconnectivity is predominant in psychosis spectrum disorders. Converging lines of evidence also suggest an interaction between dorsal anterior cingulate cortex (dACC) cortical glutamate with higher-order functional brain networks (FC) such as the default mode (DMN), dorsal attention (DAN), and executive control networks (ECN) in healthy controls (HC) and this mechanism may be impaired in psychosis. Data from 70 antipsychotic-medication naïve first-episode psychosis (FEP) and 52 HC were analyzed. 3T Proton magnetic resonance spectroscopy (1H-MRS) data were acquired from a voxel in the dACC and assessed correlations (positive FC) and anticorrelations (negative FC) of the DMN, DAN, and ECN. We then performed regressions to assess associations between glutamate + glutamine (Glx) with positive and negative FC of these same networks and compared them between groups. We found alterations in positive and negative FC in all networks (HC > FEP). A relationship between dACC Glx and positive and negative FC was found in both groups, but when comparing these relationships between groups, we found contrasting associations between these variables in FEP patients compared to HC. We demonstrated that both positive and negative FC in three higher-order resting state networks are already altered in antipsychotic-naïve FEP, underscoring the importance of also considering anticorrelations for optimal characterization of large-scale functional brain networks as these represent biological processes as well. Our data also adds to the growing body of evidence supporting the role of dACC cortical Glx as a mechanism underlying alterations in functional brain network connectivity. Overall, the implications for these findings are imperative as this particular mechanism may differ in untreated or chronic psychotic patients; therefore, understanding this mechanism prior to treatment could better inform clinicians.Clinical trial registration: Trajectories of Treatment Response as Window into the Heterogeneity of Psychosis: A Longitudinal Multimodal Imaging Study, NCT03442101 . Glutamate, Brain Connectivity and Duration of Untreated Psychosis (DUP), NCT02034253 .

Dataset Information

Enzymes in the glutamate-glutamine cycle in the anterior cingulate cortex in postmortem brain of subjects with autism.

Background

Methods

Results

Conclusion

Publications

Enzymes in the glutamate-glutamine cycle in the anterior cingulate cortex in postmortem brain of subjects with autism.

Similar Datasets

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