Changes in density of calcium‐binding‐protein‐immunoreactive GABAergic neurons in prefrontal cortex in schizophrenia and bipolar disorder
Open accessAbstract
There is evidence that GABAergic neurotransmission is altered in mental disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). The calcium‐binding proteins (CBPs) calbindin (CB), calretinin (CR), and parvalbumin (PV) are used as markers of specific subpopulations of cortical GABAergic interneurons. We examined the postmortem prefrontal cortical region (Brodmann's area 9) of patients with SCZ and BPD, and of age‐matched control subjects, excluding suicide cases. The laminar density of neurons immunoreactive (IR) for three CBPs, namely CB, CR, and PV, was quantified. The densities of CB‐IR neurons in layer 2 and PV‐IR neurons in layer 4 in the SCZ subjects decreased compared with those in the control subjects. When CBP‐IR neurons were classified according to their size, a reduction in the density of medium CB‐IR neurons in layer 2 in SCZ subjects and an increase in the density of large CR‐IR neurons in layer 2 in BPD subjects were observed. These results suggest that alterations in specific GABAergic neurons are present in mental disorders, and that such alterations may reflect the vulnerability toward the disorders.
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Among the top 100 differentially expressed genes were GABRA5 and CALB1, genes previously reported as differentially expressed in cortical tissue from schizophrenia patients, suggesting GABAergic interneuron dysfunction.
“Also included among the top 100 differentially expressed genes are the alpha 5 subunit of the GABA A receptor (GABRA5) and calbindin (CALB1), genes previously reported as differentially expressed in cortical tissue from schizophrenia patients, suggesting GABAergic interneuron dysfunction45.”
From Gene expression elucidates functional impact of polygenic risk for schizophrenia (2016) · cites this paper as [45]
The top 100 differentially expressed genes include GABRA5 and CALB1, genes previously reported as differentially expressed in cortical tissue from schizophrenia patients, suggesting GABAergic interneuron dysfunction.
“Also included among the top 100 differentially expressed genes are the alpha 5 subunit of the GABA A receptor (GABRA5) and calbindin (CALB1), genes previously reported as differentially expressed in cortical tissue from schizophrenia patients, suggesting GABAergic interneuron dysfunction45.”
From Gene expression elucidates functional impact of polygenic risk for schizophrenia (2016) · cites this paper as [45]
PVI circuits are altered in schizophrenia and autism spectrum disorder despite heterogeneity in etiology.
“Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders.”
From Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia (2017) · cites this paper as [8]
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- Authors
- Sakai, T., Oshima, A., Nozaki, Y., Ida, I., Haga, C., Akiyama, H., Nakazato, Y., & Mikuni, M.
- Affiliations
- Gunma University (JP)
- National Hospital Organization Takasaki General Medical Center (JP)
- Tokyo Institute of Psychiatry (JP)
- Corresponding author
- Sakai, Tsutomu
- ORCID
- Akiyama, Haruhiko
- Venue
- Neuropathology
- Publisher
- Wiley
- Published
- 2007-12-07
- Volume
- 28
- Issue
- 2
- Pages
- 143-150
- ISSN
- 0919-6544 (ISSN-L)
- 1440-1789
- OpenAlex
- W1975924674
- Cited by
- 118
- References
- 42
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 9 · 2019: 3 · 2018: 9 · 2017: 3 · 2016: 8 · 2015: 8 · 2014: 9 · 2013: 10 · 2012: 6
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuropathology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, bipolar disorder, GABAergic interneurons, calcium-binding proteins, calbindin, calretinin, parvalbumin, prefrontal cortex, Brodmann area 9, neuronal density, cortical layers, postmortem brain, GABAergic neurotransmission
- MeSH terms
- Bipolar Disorder, Calcium-Binding Proteins, Female, gamma-Aminobutyric Acid, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Male, Middle Aged, Neurons, Schizophrenia, Prefrontal Cortex
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