Levels of mRNAs encoding synaptic vesicle and synaptic plasma membrane proteins in the temporal cortex of elderly schizophrenic patients.
BACKGROUND
Electron microscopy and biochemical studies indicate that developmental abnormalities in synaptic organization may be present in brains of schizophrenic patients. This study determined whether these synaptic abnormalities are reflected in differential or uniform alterations in the expression of various synaptic protein genes in the left superior temporal gyrus of schizophrenic patients.


METHODS
Levels of mRNAs encoding four synaptic vesicle proteins (synaptotagmin I [p65], rab3a, synaptobrevin 1, and synaptobrevin 2) and two synaptic plasma membrane proteins (syntaxin 1A and SNAP-25) were measured postmortem in the left superior temporal gyrus from elderly (58-95 years) schizophrenic patients (n = 14) and age-matched control subjects (n = 9).


RESULTS
There were significant negative correlations between age and levels of synaptotagmin I (p65), rab3a, synaptobrevin 1, SNAP-25, and syntaxin 1A mRNAs in schizophrenic patients (-.692 < r < -.517,.003 < p <.030) but not in control subjects. Levels of all six synaptic mRNAs studied were increased in the younger (58-79 years) subgroup of schizophrenic patients compared to control subjects and older (80-95 years) subgroup of schizophrenic patients.


CONCLUSIONS
That similar abnormalities were found for mRNAs encoding different synaptic vesicle and synaptic plasma membrane proteins suggests that they reflect overall neurodevelopmental abnormalities in synaptic connectivity in the temporal cortex of schizophrenic patients rather than changes in the number of synaptic vesicles per synapse or abnormalities in a specific synaptic function.
Molecular Neurobiology Branch, National Institute on Drug Abuse, National Institutes of Health, (BPS), Baltimore, MD 21224, USA.
B P
BP
Sokolov
A A
AA
Tcherepanov
V
V
Haroutunian
K L
KL
Davis
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics; D002135:Calcium-Binding Proteins; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism* / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D050863:Synaptotagmin I; D050857:Synaptotagmins; D050827:Syntaxin 1; D013702:Temporal Lobe / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D017931:DNA Primers; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D012333:RNA, Messenger; C494212:STX1A protein, human; C494310:SYT1 protein, human; D050863:Synaptotagmin I; D050827:Syntaxin 1; D050857:Synaptotagmins