Altered Hippocampal Muscarinic M4, but Not M1, Receptor Expression from Subjects with Schizophrenia
Abstract
Background Having shown a decrease in [3H]pirenzepine binding in the hippocampus from subjects with schizophrenia, we wished to determine whether such a change in radioligand binding was associated with changes in hippocampal mRNA for the muscarinic1 (M1) and muscarinic4 (M4) receptors in tissue from different cohorts of subjects.Method The [3H]pirenzepine binding using autoradiography and in situ hybridization with oligonucleotides specific for muscarinic M1 and M4 receptors were completed using hippocampal tissue obtained postmortem from 20 control subjects and 20 subjects with schizophrenia.Results The [3H]pirenzepine binding was decreased in the dentate gyrus (p < .05), CA3 (p < .01), CA2 (p < .05), and CA1 (p < .01) regions of the hippocampus from subjects with schizophrenia. Levels of M4 mRNA varied with the diagnosis of schizophrenia (p = .01), but significant region-specific changes were not apparent. Changes in levels of mRNA for the muscarinic M1 receptor were not detected with diagnosis.Conclusions This study suggests that decreases in hippocampal [3H]pirenzepine binding in subjects with schizophrenia are most likely associated with widespread changes in expression levels of the M4 receptor. These data further implicate the hippocampal formation in the pathology of schizophrenia.
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CHRM4 has been associated with schizophrenia and implicated in cognitive flexibility and dopamine release.
“the muscarinic acetylcholine M4 receptor (CHRM4) has been associated with schizophrenia22 and implicated in cognitive flexibility23 and dopamine release24.”
From Oxytocin pathway gene networks in the human brain (2019) · cites this paper as [22]
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- Authors
- Scarr, E., Sundram, S., Keriakous, D., & Dean, B.
- Affiliations
- Mental Health Research Institute (AU)
- The University of Melbourne (AU)
- Corresponding author
- Scarr, Elizabeth
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 61
- Issue
- 10
- Pages
- 1161-1170
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W1976834251
- Cited by
- 108
- References
- 48
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 2 · 2020: 6 · 2019: 10 · 2018: 5 · 2017: 2 · 2016: 4 · 2015: 7 · 2014: 2 · 2013: 7 · 2012: 5
- FWCI
- 5.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council (209046, 400016)
- Rebecca L. Cooper Medical Research Foundation
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- schizophrenia, M4 muscarinic receptor, M1 muscarinic receptor, hippocampus, receptor mRNA expression, dentate gyrus, postmortem brain, cholinergic receptors
- MeSH terms
- Adult, Aged, Autoradiography, Female, Hippocampus, Humans, Male, Middle Aged, Pirenzepine, Radioligand Assay, RNA, Messenger, Schizophrenia, Tritium, Cohort Studies, Receptor, Muscarinic M4, Receptor, Muscarinic M1
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