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Decreased mRNA expression of netrin-G1 and netrin-G2 in the temporal lobe in schizophrenia and bipolar disorder.

ABSTRACT: The membrane-bound axon guidance molecules netrin-G1 (NTNG1) and netrin-G2 (NTNG2) play a role in synaptic formation and maintenance. Non-coding single nucleotide polymorphisms (SNPs) in both genes have been reported to be associated with schizophrenia. The main aim of this study was to determine if NTNG1 and NTNG2 mRNA expression is altered in schizophrenia or bipolar disorder, and/or influenced by disease-associated SNPs. NTNG1 and NTNG2 mRNAs were examined in the medial and inferior temporal lobe using in situ hybridization and RT-PCR in the Stanley Medical Research Institute array collection, and in rat hippocampus during development and after antipsychotic administration. NTNG1 mRNA isoforms were also examined during human brain development. For NTNG1, the G1c isoform was reduced in bipolar disorder and with a similar trend in schizophrenia; expression of four other NTNG1 isoforms was unchanged. In both schizophrenia and bipolar disorder, NTNG2 mRNA was reduced in CA3, with reductions also found in CA4 and perirhinal cortex in bipolar disorder. The SNPs did not affect NTNG1 or NTNG2 mRNA expression. Both NTNG1 and NTNG2 mRNAs were developmentally regulated, and were unaltered by haloperidol, but NTNG2 mRNA was modestly increased by clozapine. These data implicate NTNG1 and NTNG2 in the pathophysiology of schizophrenia and bipolar disorder, but do not support the hypothesis that altered mRNA expression is the mechanism by which genetic variation of NTNG1 or NTNG2 may confer disease susceptibility.

SUBMITTER: Eastwood SL

PROVIDER: S-EPMC2629613 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Decreased mRNA expression of netrin-G1 and netrin-G2 in the temporal lobe in schizophrenia and bipolar disorder.

Eastwood Sharon L SL Harrison Paul J PJ

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20070516 4

The membrane-bound axon guidance molecules netrin-G1 (NTNG1) and netrin-G2 (NTNG2) play a role in synaptic formation and maintenance. Non-coding single nucleotide polymorphisms (SNPs) in both genes have been reported to be associated with schizophrenia. The main aim of this study was to determine if NTNG1 and NTNG2 mRNA expression is altered in schizophrenia or bipolar disorder, and/or influenced by disease-associated SNPs. NTNG1 and NTNG2 mRNAs were examined in the medial and inferior temporal ...[more]

PMID: 17507910

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Project description:Purpose:Modern neuroimaging techniques allow investigating brain structures and substances involved in the pathophysiology of mental disorders, trying to find new markers of these disorders. To better understanding of the pathophysiology and differential diagnosis of schizophrenia and bipolar disorder, this study was conducted to assess the neurochemical alterations in the frontal and temporal lobes in hospitalized patients with schizophrenia and bipolar disorder. Methods:Twenty-one subjects with schizophrenia (paranoid and differentiated types), 16 subjects with bipolar I disorder (manic, depressive, and mixed episode), and 20 healthy subjects were studied. Magnetic resonance (MR) imaging and proton resonance magnetic spectroscopy (1H MRS) were performed on a 1.5?T scanner. Voxels of 8?cm3 were positioned in the left frontal and left temporal lobes. Results:Glx/H2O (GABA, glutamine, and glutamate/nonsuppressed water signal) ratios were significantly increased in the left temporal lobe in schizophrenia, but not in bipolar disorder, compared with controls. Cho/H2O (choline/nonsuppressed water signal) ratios in the left frontal lobe had a tendency to increase in bipolar disorder and schizophrenia, relative to controls. A lower temporal lobe NAA/H2O ratio in mixed than in manic and depressive episode of bipolar patients was also found. No other significant differences were found among three studied groups as regards NAA, Cr, and mI ratios. Conclusions:Our results partially confirm the role of a glutamatergic system in schizophrenia, however, only in a temporal lobe. We also point to the importance of the choline-containing compounds (marker of cellular density) in the frontal lobe of patients suffering from bipolar disorder and schizophrenia. We also found the deleterious effect of mixed bipolar episode on the integrity and functioning of the temporal lobe. Glutamatergic left temporal spectroscopic changes may potentially help in differential diagnosis of schizophrenia from bipolar disorder.

Dataset Information

Decreased mRNA expression of netrin-G1 and netrin-G2 in the temporal lobe in schizophrenia and bipolar disorder.

Publications

Decreased mRNA expression of netrin-G1 and netrin-G2 in the temporal lobe in schizophrenia and bipolar disorder.

Similar Datasets

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