Altered expression of apoptotic factors and synaptic markers in postmortem brain from bipolar disorder patients.
Bipolar disorder (BD) is a progressive psychiatric disorder characterized by recurrent changes of mood and is associated with cognitive decline. There is evidence of excitotoxicity, neuroinflammation, upregulated arachidonic acid (AA) cascade signaling and brain atrophy in BD patients. These observations suggest that BD pathology may be associated with apoptosis as well as with disturbed synaptic function. To test this hypothesis, we measured mRNA and protein levels of the pro-apoptotic (Bax, BAD, caspase-9 and caspase-3) and anti-apoptotic factors (BDNF and Bcl-2) and of pre- and post-synaptic markers (synaptophysin and drebrin), in postmortem prefrontal cortex (Brodmann area 9) from 10 BD patients and 10 age-matched controls. Consistent with the hypothesis, BD brains showed significant increases in protein and mRNA levels of the pro-apoptotic factors and significant decreases of levels of the anti-apoptotic factors and the synaptic markers, synaptophysin and drebrin. These differences may contribute to brain atrophy and progressive cognitive changes in BD.
Kim
Hyung-Wook
HW
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Rapoport
Stanley I
SI
Rao
Jagadeesh S
JS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D001284:Atrophy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D018450:Disease Progression; D015536:Down-Regulation / Q000502:physiology; D004660:Encephalitis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D016708:Synaptophysin; C053386:drebrins; D016718:Arachidonic Acid