Increased excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from bipolar disorder patients.
Reports of cognitive decline, symptom worsening and brain atrophy in bipolar disorder (BD) suggest that the disease progresses over time. The worsening neuropathology may involve excitotoxicity and neuroinflammation. We determined protein and mRNA levels of excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from 10 BD patients and 10 age-matched controls. The brain tissue was matched for age, postmortem interval and pH. The results indicated statistically significant lower protein and mRNA levels of the N-methyl-D-aspartate receptors, NR-1 and NR-3A, but significantly higher protein and mRNA levels of interleukin (IL)-1beta, the IL-1 receptor (IL-1R), myeloid differentiation factor 88, nuclear factor-kappa B subunits, and astroglial and microglial markers (glial fibrillary acidic protein, inducible nitric oxide synthase, c-fos and CD11b) in postmortem frontal cortex from BD compared with control subjects. There was no significant difference in mRNA levels of tumor necrosis factor alpha or neuronal nitric oxide synthase in the same region. These data show the presence of excitotoxicity and neuroinflammation in BD frontal cortex, with particular activation of the IL-R cascade. The changes may account for reported evidence of disease progression in BD and be a target for future therapy.
Rao
J S
JS
Brain Physiology and Metabolism Section, NIA, NIH Bethesda, Bethesda, MD 20892, USA. jrao@mail.nih.gov
Harry
G J
GJ
Rapoport
S I
SI
Kim
H W
HW
D000328:Adult; D001714:Bipolar Disorder / Q000473:pathology*; D039481:CD11b Antigen / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011180:Postmortem Changes; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D013223:Statistics as Topic
D039481:CD11b Antigen; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D053594:Myeloid Differentiation Factor 88; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D016194:Receptors, N-Methyl-D-Aspartate