Region-specific alteration of GABAergic markers in the brain of heterozygous reeler mice
Abstract
Heterozygous reeler mice (HRM), haploinsufficient for reelin, have been proposed to be a genetic mouse model of schizophrenia. Beside behavioural similarities, HRM also demonstrate several neuroanatomical traits similar to patients suffering from schizophrenia. In the present study using immunocytochemical procedures, we investigated HRM and wild-type mice (WT) for differences in the numbers and densities of glutamic acid decarboxylase (GAD)67 and parvalbumin (PARV)-immunoreactive (IR) neurons in the hippocampus, tyrosine hydroxylase (TH)-IR neurons in the ventral tegmental area (VTA) and substantia nigra (SN), and serotonin transporter (5-HT-T)-IR neurons of the raphe nuclei. We found that HRM, compared with WT, show a significant decrease of GAD67-IR neurons in hippocampal subregion CA1 [stratum pyramidale (SP)], CA2 [stratum oriens (SO), stratum pyramidale (SP) and stratum radiatum (SR)] and dentate gyrus [granule cell layer (GL)], and also a significant decrease of PARV-containing neurons in CA1 (SO, SP) and CA2 (SP). No morphological differences were found in the SN/VTA or raphe nuclei. In conclusion, these results support a hippocampal γ-aminobutyric acid (GABA)ergic dysfunction in HRM as previously described by other authors, and may be based on a downregulation of GAD67 and PARV expressions. In summary, the reelin haploinsufficient mouse may provide a useful model for studying the interaction between reelin and hippocampal GABAergic system, its effect on dendritic spine maturation and plasticity related to schizophrenia.
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Reeler heterozygous mice with reduced reelin show decreased GAD67 and fewer GABAA and GABAB receptors in whole brain and hippocampus.
“Reeler heterozygous mice, which are haploinsufficient for reelin, exhibit decreased GAD 67 [138] and reduced GABAA and GABAB receptors in the whole brain and hippocampus, respectively [139].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [138]
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- Authors
- Nullmeier, S., Panther, P., Dobrowolny, H., Frotscher, M., Zhao, S., Schwegler, H., & Wolf, R.
- Affiliations
- Otto-von-Guericke-Universität Magdeburg (DE)
- University of Freiburg (DE)
- Ruhr University Bochum (DE)
- Corresponding author
- Nullmeier, S.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2011-01-13
- Volume
- 33
- Issue
- 4
- Pages
- 689-698
- ISSN
- 0953-816X (ISSN-L)
- OpenAlex
- W1582016951
- Cited by
- 43
- References
- 68
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 5 · 2013: 2 · 2012: 6
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (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, GABAergic neurons, GAD67, parvalbumin, hippocampus, CA1, dentate gyrus, ventral tegmental area, substantia nigra, raphe nuclei, tyrosine hydroxylase, serotonin transporter, dendritic spine maturation, dendritic plasticity
- MeSH terms
- Reelin Protein, Animals, Brain, Female, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Humans, Male, Mice, Neurologic Mutants, Nerve Tissue Proteins, Neurons, Schizophrenia, Serine Endopeptidases, Tyrosine 3-Monooxygenase, Biomarkers, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Mice
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