Cited by 433Bipolar Disorder and TreatmentTryptophan and brain disordersNeuroinflammation and Neurodegeneration Mechanisms

Increased excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from bipolar disorder patients

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Rao, J S, Harry, G J, Rapoport, S I, Kim, H W·2010·Molecular Psychiatry

Abstract

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.

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Crossref · 10.1038/mp.2009.47

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  • Evidence of microglial and astroglial activation in several brain regions including frontal cortex, anterior cingulate cortex and thalamus in post-mortem studies of patients with depression has been described.

    “evidence of microglial and astroglial activation in several brain regions including frontal cortex, anterior cingulate cortex (ACC) and thalamus in post-mortem studies of patients with depression have been described57–59,60.”

    From The role of inflammation in depression: from evolutionary imperative to modern treatment target (2016) · cites this paper as [57]

    The Results section reports increased astrocyte and microglial markers in postmortem frontal cortex from patients with bipolar disorder. It does not establish the claim for anterior cingulate cortex or thalamus, or for patients with depression more broadly. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • Prior work has identified differential activation of glial and neural-immune processes in brains of patients with psychiatric disorders.

    “Previous work has identified differential activation of glial and neural-immune processes in brain from patients with psychiatric disorders (16, 52, 57, 66–69)”

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Authors
Rao, J. S., Harry, G. J., Rapoport, S. I., & Kim, H. W.
Affiliations
National Institutes of Health (US)
Corresponding author
Rao, J S
Venue
Molecular Psychiatry
Published
2009-06-02
Volume
15
Issue
4
Pages
384-392
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
OpenAlex
W2014858274
Cited by
432
References
54
Citations by year
2026: 12 · 2025: 10 · 2024: 18 · 2023: 20 · 2022: 23 · 2021: 35 · 2020: 31 · 2019: 26 · 2018: 26 · 2017: 29 · 2016: 38 · 2015: 48 · 2014: 25 · 2013: 25 · 2012: 26
FWCI
13.61
Type
journal article
Language
en
Open access
Locations
  • Molecular Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (Z99 AG999999)
  • National Institute on Aging
  • National Institute of Mental Health (R24MH068855)
  • National Cancer Institute
  • National Institute of Environmental Health Sciences
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
bipolar disorder, excitotoxicity, neuroinflammation, frontal cortex, NMDA receptor, NR1, IL-1β, IL-1 receptor, myeloid differentiation factor 88, NF-κB, microglia, astrocytes, glial fibrillary acidic protein, inducible nitric oxide synthase, c-fos, CD11b, disease progression, postmortem brain
MeSH terms
Adult, Bipolar Disorder, Female, Frontal Lobe, Gene Expression Regulation, Humans, Male, Middle Aged, Nerve Tissue Proteins, Nuclear Proteins, Postmortem Changes, RNA, Messenger, Statistics as Topic, Case-Control Studies, Receptors, N-Methyl-D-Aspartate, Proto-Oncogene Proteins c-fos, Receptors, Interleukin-1, Inflammation Mediators, CD11b Antigen, Interleukin-1beta, Myeloid Differentiation Factor 88

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