Disruption of PLC-$beta;1-Mediated Signal Transduction in Mutant Mice Causes Age-Dependent Hippocampal Mossy Fiber Sprouting and Neurodegeneration
Abstract
Aberrant reorganization of hippocampal mossy fibers occurs in human temporal lobe epilepsy and rodent epilepsy models. We generated a mouse model showing massive late-onset aberrant mossy fiber sprouting in the adult hippocampus. The mutation in this mouse model derives from an intronic insertion of transgene DNA in the mouse PLC-beta1 gene (PLC-beta 1(-/-)(TC) mutation) leading to a splice mutation of the PLC-beta 1 gene and a complete loss of downstream PLC-beta 1 expression. PLC-beta 1(-/-)(TC) mutants develop a loss of NMDA-receptors in the stratum oriens of region CA1, apoptotic neuronal death, and reduced hippocampal PKC activity. The phenotype of these mice further consists of a late-onset epileptiform hyperexcitability, behavioral modifications in a radial maze and in an open field, female nurturing defect, and male infertility. In the present study, we provide evidence that the arising of the behavioral phenotype in PLC-beta 1(-/-)(TC) mice correlates in time with the development of the aberrant mossy fiber projections and that the disruption of the PLC-beta 1-mediated signal transduction pathway may lead to a functional cholinergic denervation, which could cause hippocampal remodeling and, in consequence, epileptiform hyperexcitability.
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PLCβ1 has been implicated in control of neuronal function and enhancement of glucose-stimulated insulin secretion in pancreatic β-cells downstream of specific GPCRs.
“Among many roles, ubiquitously expressed PLCβ1 enzyme has been implicated in control of neuronal function and the enhancement of glucose-stimulated insulin secretion in pancreatic β-cells downstream of specific GPCRs in these different cell types [36–40].”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [38]
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References 89 · Cited by 50
- Authors
- BOHM, D.
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2002-12
- Volume
- 21
- Issue
- 4
- Pages
- 584-601
- ISSN
- 1044-7431 (ISSN-L)
- OpenAlex
- W1980702456
- Cited by
- 50
- References
- 89
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 4 · 2022: 6 · 2021: 2 · 2020: 4 · 2019: 2 · 2017: 1 · 2016: 2 · 2014: 1 · 2013: 4 · 2012: 4
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- GRO (submittedVersion)
- Funders
- Ministerul Cercetării, Inovării şi Digitalizării
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- PLCB1, mossy fiber sprouting, hippocampus, temporal lobe epilepsy, neuronal apoptosis, cholinergic denervation, neurodegeneration, mouse mutants, infertility, maternal behavior
- MeSH terms
- Aging, Animals, Carbachol, Chromosome Mapping, Disease Models, Animal, Epilepsy, Temporal Lobe, Female, Isoenzymes, Male, Mice, Neurologic Mutants, Mutation, Nerve Degeneration, Neuronal Plasticity, Type C Phospholipases, Protein Kinase C, Recombinant Fusion Proteins, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Alternative Splicing, Mice, Knockout, Transgenes, Mossy Fibers, Hippocampal, Growth Cones, Mice, Phospholipase C beta
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