Our findings thus demonstrate neuronal SR association with DISC1 and its agglomerates, which can be modulated by d-Serine, thereby validating a novel neuronal SR-DISC1 complex responsive to NMDAR activation and providing a molecular mechanism by which pathways implicated in schizophrenia converge.
The disrupted-in-schizophrenia 1 (DISC1) protein has been implicated in a range of biological mechanisms underlying chronic mental disorders such as schizophrenia.
We found two SNPs (rs11122324 and rs2793091) of DISC1 may be specifically associated with multiplex schizophrenia patients with deficient sustained attention.
Altered DISC1 distribution or function caused by aberrant intermolecular interactions may contribute to information processing characteristics in schizophrenia.
As with other genetic variants that present an increased risk for disease, mutations of the DISC1 gene have been implicated in the molecular intersection of schizophrenia and numerous other major psychiatric illnesses.
Using isogenic cell lines in which the DISC1 mutation is either introduced in the control cell line, or rescued in the schizophrenia cell line, we ascribe most of these changes to a direct effect of the presence of the DISC1 mutation.
In addition, the DISC1 interactome in iPSC-derived neural progenitor cells associates in a connected network containing proteins found to harbor de novo mutations in patients affected by schizophrenia and contains a subset of novel interactions that are known to harbor syndromic mutations in neurodevelopmental disorders.
Besides specific phenotypes such as DISC1 protein pathology, abnormal dopamine homeostasis, and changes in neuroanatomy and behavior, this animal model also shows subtle disturbances in overarching signaling pathways relevant for schizophrenia.
We found increased lactate in the dorsolateral prefrontal cortex (p = 0.043, n = 16/group) in schizophrenia, as well as in frontal cortical neurons differentiated from a subject with schizophrenia with the DISC1 mutation (p = 0.032).
Disrupted-in-schizophrenia 1 (DISC1) is a key protein involved in behavioral processes and various mental disorders, including schizophrenia and major depression.
The discovery of a mutation in the disrupted in schizophrenia 1 (DISC1) gene in the 129 mouse strain suggests that these mice may be exploited as a 'naturally occurring' model of schizophrenia.
A balanced chromosomal translocation disrupting DISC1 (Disrupted in Schizophrenia 1) gene has been linked to psychiatric diseases, such as major depression, bipolar disorder and schizophrenia.
Consistent with findings in hDISC1 mice, several hindbrain OLG markers (PRX, LAMA1, and MPZ) were significantly upregulated in the superior temporal cortex of persons with SZ.
This meta-analysis indicated that rs3737597 of DISC1 was significantly associated with schizophrenia in Europeans, and it can be suggested as an ethnic-specific risk genetic factor.
The molecular defects of disrupted-in-schizophrenia-1 (DISC1), P53, brain-derived neurotrophic factor (BDNF) and C-X-C chemokine receptors type 4 (CXCR4) involved in schizophrenia pathogenesis might play opposite roles in glioma development.
Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to determine the correlation between DISC1 gene polymorphisms and SCZ susceptibility.
The neuromodulatory gene DISC1 is disrupted by a t(1;11) translocation that is highly penetrant for schizophrenia and affective disorders, but how this translocation affects DISC1 function is incompletely understood.