Related Experiment Videos
Changes in relative levels of specific brain mRNA species associated with schizophrenia and depression
C W Perrett1, S A Whatley, I N Ferrier
1Department of Biochemistry, Institute of Psychiatry, London, U.K.
Abstract:
Total cellular polyadenylated RNA (poly(A)+ RNA, mRNA) was prepared after guanidinium thiocyanate extraction of frozen brain tissue from age-matched controls and patients suffering from schizophrenia and unipolar depression. These mRNA populations were analysed by in vitro translation followed by two-dimensional gel analysis. Data were obtained from fluorograms derived from 10 different schizophrenic patients, 10 different controls and 5 different depressive patients. The relative concentrations of mRNA species coding for 4 translation products (33 kDa, pI 5.8; 26 kDa, pI 5.8; 35 kDa, pI 7.1; 23 kDa, pI 6.1) were significantly reduced in schizophrenia compared to controls when determined by computerised image analysis of the fluorograms. In the case of depression, the relative concentrations of mRNA species coding for 6 translation products were significantly altered, 4 being increased (38 kDa, pI 6.2, 17 kDa, pI 5.7, 35 kDa, pI 7.1; 23 kDa, pI 6.1) and two decreased (34 kDa, pI 6.2; 33 kDa, pI 5.8). Three translation products were altered in both schizophrenia and depression, one (33 kDa, pI 5.8) being altered according to the same trend, a decrease relative to controls, but two (35 kDa, pI 7.1; 23 kDa, pI 6.1) being altered differently in schizophrenia (reduced) and depression (increased). The effects of post mortem delay, mode of death and drug treatment on mRNA composition were also examined and found not to affect the levels of these translation products significantly. The significance of these changes will be discussed in relation to their relevance of biological mechanisms in the psychoses.
Insights
Messenger RNA (mRNA) levels for specific proteins are altered in the brains of individuals with schizophrenia and depression. These changes may offer insights into the biological mechanisms underlying psychosis.
Area of Science:
- Neuroscience
- Molecular Biology
- Psychiatry
Background:
- Schizophrenia and unipolar depression are complex psychiatric disorders with unclear biological underpinnings.
- Gene expression alterations in brain tissue are potential contributors to these conditions.
Purpose of the Study:
- To investigate differences in messenger RNA (mRNA) populations between control subjects and patients with schizophrenia and unipolar depression.
- To identify specific mRNA species whose translation products are altered in these psychiatric conditions.
Main Methods:
- Extraction of polyadenylated RNA (poly(A)+ RNA, mRNA) from frozen brain tissue.
- Analysis of mRNA populations using in vitro translation followed by two-dimensional gel electrophoresis.
- Quantification of translation product concentrations via computerized image analysis of fluorograms.
Main Results:
- Significant reductions in mRNA species coding for four translation products were observed in schizophrenia patients compared to controls.
- In depression, mRNA species for six translation products were altered, with four increased and two decreased.
- Three translation products showed altered expression in both conditions, with distinct patterns for two of them.
Conclusions:
- Specific mRNA expression changes are associated with schizophrenia and unipolar depression.
- These findings contribute to understanding the molecular pathology of psychoses.
- Post mortem factors did not significantly influence the observed mRNA alterations.