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Phospholipase C beta 1 expression in the dorsolateral prefrontal cortex from patients with schizophrenia at different
Madhara Udawela1, Elizabeth Scarr, Anthony J Hannan
1Rebecca L. Cooper Research Laboratories, Mental Health Research Institute, Parkville, Victoria, Australia. m.udawela@mhri.edu.au
Objective:
Our recent microarray study detected decreases in the expression of phospholipase C beta 1 mRNA in the dorsolateral prefrontal cortex from subjects with schizophrenia at different stages of illness. Thus we aimed to validate and extend these findings.
Method:
We measured levels of mRNA and protein for phospholipase C beta 1 variant a and b using real-time PCR and western blot analysis, respectively, in the dorsolateral prefrontal cortex from subjects with schizophrenia, who had a short (< 7 years) or long (> 22 years) duration of illness.
Results:
Compared to age/sex matched controls, levels of phospholipase C beta 1 variant a and b mRNAs were decreased (-33% and -50%, respectively) in short duration schizophrenia. By contrast, only variant a mRNA was decreased (-24%) in long duration schizophrenia. There was no significant difference in the protein levels of either phospholipase C beta 1 variant in schizophrenia, irrespective of duration of illness (variant a; P = 0.84, variant b; P = 0.73).
Conclusion:
Our data confirm that phospholipase C beta 1 transcript levels are decreased in the dorsolateral prefrontal cortex from subjects with schizophrenia. However, the changes in levels of mRNA do not translate into a change at the level of protein. It is possible protein expression is regulated independently of mRNA and it remains to be determined whether there is a functional consequence of this change in mRNA relating to the pathophysiology of schizophrenia.
Insights
Schizophrenia is linked to lower phospholipase C beta 1 mRNA in the brain, but protein levels remain unchanged. This suggests independent regulation and an unknown functional impact on schizophrenia pathophysiology.
Area of Science:
- Neuroscience
- Molecular Psychiatry
- Genetics
Background:
- Previous microarray studies indicated reduced phospholipase C beta 1 (PLCβ1) mRNA in schizophrenia.
- PLCβ1 is crucial for neuronal function and implicated in various brain disorders.
Purpose of the Study:
- To validate and extend findings on PLCβ1 mRNA expression in schizophrenia.
- To investigate PLCβ1 protein levels in relation to illness duration.
Main Methods:
- Real-time PCR and Western blot were used to quantify PLCβ1 mRNA and protein variants a and b.
- Samples were from the dorsolateral prefrontal cortex of schizophrenia patients (short/long duration) and controls.
Main Results:
- PLCβ1 mRNA variants a and b were significantly decreased in short-duration schizophrenia.
- Only variant a mRNA showed a decrease in long-duration schizophrenia.
- No significant differences in PLCβ1 protein levels were observed between patients and controls.
Conclusions:
- Confirms decreased PLCβ1 mRNA in schizophrenia dorsolateral prefrontal cortex.
- mRNA changes do not correlate with protein levels, suggesting post-transcriptional regulation.
- The functional significance of altered PLCβ1 mRNA in schizophrenia remains to be elucidated.
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