The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Increased excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from bipolar disorder patients
Open accessAbstract
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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“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]
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“Previous work has identified differential activation of glial and neural-immune processes in brain from patients with psychiatric disorders (16, 52, 57, 66–69)”
From Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder (2018) · cites this paper as [69]
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3 retracted
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Self-citationRetractedDecreased GRK3 but not GRK2 expression in frontal cortex from bipolar disorder patients
Rao, J. S., Rapoport, S. I., & Kim, H. (2009) · The International Journal of Neuropsychopharmacology · doi:10.1017/s146114570900025x · Cited by 22
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Cited by
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The role of inflammation in depression: from evolutionary imperative to modern treatment target
Miller, A. H., & Raison, C. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2015.5 · Cited by 3,942
Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder
Gandal, M. J., Zhang, P., Hadjimichael, E., Walker, R. L., Chen, C., Liu, S., Won, H., van Bakel, H., Varghese, M., Wang, Y., et al. (2018) · Science · doi:10.1126/science.aat8127 · Cited by 1,247
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Najjar, S., Pearlman, D. M., Alper, K., Najjar, A., & Devinsky, O. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-43 · Cited by 733
The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders
Réus, G. Z., Fries, G. R., Stertz, L., Badawy, M., Passos, I. C., Barichello, T., Kapczinski, F., & Quevedo, J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.018 · Cited by 594
Metadata
- Authors
- Rao, J. S., Harry, G. J., Rapoport, S. I., & Kim, H. W.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Rao, J S
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2009-06-02
- Volume
- 15
- Issue
- 4
- Pages
- 384-392
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC2844920
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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