Molecular Profiles of Pyramidal Neurons in the Superior Temporal Cortex in Schizophrenia
Open accessAbstract
Disrupted synchronized oscillatory firing of pyramidal neuronal networks in the cerebral cortex in the gamma frequency band (i.e., 30-100 Hz) mediates many of the cognitive deficits and symptoms of schizophrenia. In fact, the density of dendritic spines and the average somal area of pyramidal neurons in layer 3 of the cerebral cortex, which mediate both long-range (associational) and local (intrinsic) corticocortical connections, are decreased in subjects with this illness. To explore the molecular pathophysiology of pyramidal neuronal dysfunction, we extracted ribonucleic acid (RNA) from laser-captured pyramidal neurons from layer 3 of Brodmann's area 42 of the superior temporal gyrus (STG) from postmortem brains from schizophrenia and normal control subjects. We then profiled the messenger RNA (mRNA) expression of these neurons, using microarray technology. We identified 1331 mRNAs that were differentially expressed in schizophrenia, including genes that belong to the transforming growth factor beta (TGF-β) and the bone morphogenetic proteins (BMPs) signaling pathways. Disturbances of these signaling mechanisms may in part contribute to the altered expression of other genes found to be differentially expressed in this study, such as those that regulate extracellular matrix (ECM), apoptosis, and cytoskeletal and synaptic plasticity. In addition, we identified 10 microRNAs (miRNAs) that were differentially expressed in schizophrenia; enrichment analysis of their predicted gene targets revealed signaling pathways and gene networks that were found by microarray to be dysregulated, raising an interesting possibility that dysfunction of pyramidal neurons in schizophrenia may in part be mediated by a concerted dysregulation of gene network functions as a result of the altered expression of a relatively small number of miRNAs. Taken together, findings of this study provide a neurobiological framework within which specific hypotheses about the molecular mechanisms of pyramidal cell dysfunction in schizophrenia can be formulated.
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Expression of several enzymes involved in extracellular matrix degradation is increased in the temporal cortex in schizophrenia.
“Interestingly, the expression of several enzymes involved in extracellular matrix (ECM) degradation is increased in the temporal cortex in schizophrenia (Pietersen et al, 2014).”
From Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia (2016) · cites this paper as Pietersen et al, 2014
In schizophrenia subjects, superior temporal gyrus gene expression profiling showed altered mRNA levels of MMPs and ADAMTSs, including MMP16.
“Consistent with this hypothesis, a recent gene expression profiling study of the superior temporal gyrus in subjects with SZ showed altered mRNA expression of MMPs and ADAMTSs, including MMP16 (Pietersen et al., 2014).”
From Losing the sugar coating: Potential impact of perineuronal net abnormalities on interneurons in schizophrenia (2015) · cites this paper as Pietersen et al., 2014
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Cerebellar Deficits and Hyperactivity in Mice Lacking Smad4
Zhou, Y.-X., Zhao, M., Li, D., Shimazu, K., Sakata, K., Deng, C., & Lu, B. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308287200 · Cited by 68 · see citing works
OP-1 Enhances Dendritic Growth from Cerebral Cortical Neurons in Vitro
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Regulation of the Postsynaptic Cytoskeleton: Roles in Development, Plasticity, and Disorders
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Cyclic AMP enhances Smad-mediated BMP signaling through PKA-CREB pathway
Ohta, Y., Nakagawa, K., Imai, Y., Katagiri, T., Koike, T., & Takaoka, K. (2008) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-008-0850-8 · Cited by 47 · see citing works
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Obtaining High Quality RNA from Single Cell Populations in Human Postmortem Brain Tissue
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Regulation of cell cycle and DNA repair in post-mitotic GABA neurons in psychotic disorders
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Association study in the 5q31-32 linkage region for schizophrenia using pooled DNA genotyping
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Neuronal Type-Specific Gene Expression Profiling and Laser-Capture Microdissection
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Flagged first, then by citations
Research works printed but not linked: 1
- [26]Derynck R. Miyazono K. o (2008) The TGF-[beta] family Cold Spring Harbor, NY Cold Spring Harbor Laboratory Press PMC4852809 27141051
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Clusterin in Alzheimer’s Disease: Mechanisms, Genetics, and Lessons From Other Pathologies
Foster, E. M., Dangla-Valls, A., Lovestone, S., Ribe, E. M., & Buckley, N. J. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00164 · Cited by 381 · see citing works
Enwright, J. F., Sanapala, S., Foglio, A., Berry, R., Fish, K. N., & Lewis, D. A. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.24 · Cited by 223 · see citing works
Smigielski, L., Jagannath, V., Rössler, W., Walitza, S., & Grünblatt, E. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0601-3 · Cited by 168 · see citing works
Berretta, S., Pantazopoulos, H., Markota, M., Brown, C., & Batzianouli, E. T. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2014.12.040 · Cited by 152 · see citing works
Perineuronal nets and schizophrenia: The importance of neuronal coatings
Bitanihirwe, B. K. Y., & Woo, T.-U. W. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.03.018 · Cited by 95 · see citing works
Self-citation
- Authors
- Pietersen, C. Y., Mauney, S. A., Kim, S. S., Lim, M. P., Rooney, R. J., Goldstein, J. M., Petryshen, T. L., Seidman, L. J., Shenton, M. E., McCarley, R. W., Sonntag, K.-C., & Woo, T.-U. W.
- Affiliations
- Harvard University (US)
- McLean Hospital (US)
- Genome Explorations Inc.
- Brigham and Women's Hospital (US)
- Massachusetts General Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Woo, Tsung-Ung W.
- ORCID
- Venue
- Journal of Neurogenetics
- Publisher
- Informa UK Limited
- Published
- 2014-04-10
- Volume
- 28
- Issue
- 1-2
- Pages
- 53-69
- ISSN
- 0167-7063 (ISSN-L)
- 1563-5260
- PMC
- PMC4196521
- OpenAlex
- W1975668251
- Cited by
- 87
- References
- 114
- Citations by year
- 2026: 5 · 2024: 6 · 2023: 12 · 2022: 2 · 2021: 5 · 2020: 13 · 2019: 8 · 2018: 6 · 2017: 3 · 2016: 13 · 2015: 10 · 2014: 4
- FWCI
- 7.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurogenetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Figshare (cc-by)
- Funders
- National Institute of Mental Health (P50MH080272, R01MH076060)
- National Center for Research Resources (P51RR000168)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- schizophrenia, pyramidal neurons, superior temporal gyrus, layer 3, mRNA expression profiling, microRNA, TGF-beta signaling, bone morphogenetic proteins, extracellular matrix, apoptosis, synaptic plasticity, gene networks, postmortem brain
- MeSH terms
- Adult, Aged, Aged, 80 and over, Cytoskeleton, Extracellular Matrix, Female, Humans, Male, Middle Aged, Schizophrenia, Temporal Lobe, Signal Transduction, Transforming Growth Factor beta, Apoptosis, Pyramidal Cells, Bone Morphogenetic Proteins, Gene Expression Profiling, MicroRNAs, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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