Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In searching for genes dysregulated in schizophrenia, we measured the expression of the two splice variants of calcium/calmodulin-dependent protein kinase II (CaMKIIalpha and CaMKIIbeta) in postmortem frontal cerebral cortex tissues from patients who had died with schizophrenia, bipolar disorder, or severe depression. The mRNA levels of expression of these two splice variants were measured by real-time Quantitative PCR, using an Mx4000 instrument. The values for the expression of CaMKIIalpha and CaMKIIbeta were normalized by the expression of beta-glucuronidase in the tissues. The expression of CaMKIIalpha was significantly elevated in the depression tissues by 29%. The expression of CaMKIIbeta was significantly elevated in the schizophrenia tissues by 27%, and in the depression tissues by 36%. Because CaMKIIbeta influences the expression of many neuroreceptors and influences neural outgrowth and pruning, its altered expression in the cerebral cortex in schizophrenia or depression may contribute to these diseases.
 ...
PMID:Increased expression of calcium/calmodulin-dependent protein kinase IIbeta in frontal cortex in schizophrenia and depression. 1624 65

It is known that RGS9-2 gene knockout mice show supersensitivity to DA and have a marked elevation in the proportion of DA D2 receptors in the high-affinity state for DA (D2(High) receptors). As this is a similar profile to that observed in the CNS from subjects with schizophrenia, we examined whether postmortem CNS tissue from subjects with the disorder and brain striata from an animal model of psychosis or schizophrenia (the amphetamine-sensitized rat) had altered levels of RGS9-2. The mRNA for RGS9-2 in 29 control hippocampi was 0.185 +/- 0.015 fg per fg of beta-glucuronidase mRNA (average +/- SE), while that in 29 schizophrenia hippocampi was 0.145 +/- 0.015 fg per fg of beta-glucuronidase mRNA (average +/- SE), a reduction of 22%. Of the many receptor-regulating genes related to G proteins, and of 11 RGS genes, RGS9-2 was the most reduced in the amphetamine-sensitized rat striatum. The reduced levels of RGS9-2 expression in both an animal model of schizophrenia and a postmortem schizophrenia brain provide further evidence implicating RGS9-2 as a candidate gene in schizophrenia.
 ...
PMID:Consistent with dopamine supersensitivity, RGS9 expression is diminished in the amphetamine-treated animal model of schizophrenia and in postmortem schizophrenia brain. 1731 83

Recent studies have shown that the elevation in calcium/calmodulin-dependent protein kinase II (CaMKII) may play an important role in amphetamine-induced dopamine release, as well as in the increase of dopamine D2 receptor high-affinitystates in psychosis. Because amphetamine sensitization is a widely used animal model of psychosis or schizophrenia, we investigated whether amphetamine sensitization results in an overall increase in the alpha and beta subunits of CaMKII. To answer this question, we measured CaMKII alpha and beta subunit mRNA expression using Real-Time Quantitative PCR in amphetamine-sensitized rat striata, compared to saline-treated controls. The results were then standardized to beta-glucuronidase, a housekeeping gene. Our results showed a statistically significant increase in the CaMKII beta subunit, and an increase in the alpha subunit which did not reach statistical significance. Because the levels of both CaMKIIbeta and CaMKIIalpha play a role in neuronal function and synapse formation, the present finding of an elevated level of CaMKII beta and alpha subunit mRNA in the amphetamine-sensitized model of psychosis points to the possibility of dysregulated levels of CaMKII subunits in human psychosis.
 ...
PMID:Amphetamine sensitization elevates CaMKIIbeta mRNA. 1760 7