Changes in relative levels of specific brain mRNA species associated with schizophrenia and depression.
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.
Department of Biochemistry, Institute of Psychiatry, London, U.K.
C W
CW
Perrett
S A
SA
Whatley
I N
IN
Ferrier
R M
RM
Marchbanks
D000368:Aged; D002540:Cerebral Cortex / Q000378:metabolism*; D003643:Death; D003866:Depressive Disorder / Q000235:genetics / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005475:Flupenthixol / Q000494:pharmacology; D006801:Humans; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D011061:Poly A / Q000378:metabolism; D011180:Postmortem Changes; D014176:Protein Biosynthesis; D012313:RNA / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D012156:Reticulocytes / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D005475:Flupenthixol