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Derivation of Glial Restricted Precursors from E13 mice
Published on: June 20, 2012
Mouse brains deficient in neuronal PDGF receptor-beta develop normally but are vulnerable to injury
Yoko Ishii1, Takeshi Oya, Lianshun Zheng
1Department of Pathology, Faculty of Medicine, University of Toyama, Toyama, Japan.
Abstract:
Platelet-derived growth factors (PDGFs) and PDGF receptors (PDGFRs) are widely expressed in the mammalian CNS, though their functional significance remains unclear. The corresponding null-knockout mutations are lethal. Here, we developed novel mutant mice in which the gene encoding the beta subunit of PDGFR (PDGFR-beta) was genetically deleted in CNS neurons to elucidate the role of PDGFR-beta, particularly in the post-natal stage. Our mutant mice reached adulthood without apparent anatomical defects. In the mutant brain, immunohistochemical analyses showed that PDGFR-beta detected in neurons and in the cells in the subventricular zone of the lateral ventricle in wild-type mice was depleted, but PDGFR-beta detected in blood vessels remained unaffected. The cerebral damage after cryogenic injury was severely exacerbated in the mutants compared with controls. Furthermore, TdT-mediated dUTP-biotin nick end labeling (TUNEL)-positive neuronal cell death and lesion formation in the cerebral hemisphere were extensively exacerbated in our mutant mice after direct injection of NMDA without altered NMDA receptor expression. Our results clearly demonstrate that PDGFR-beta expressed in neurons protects them from cryogenic injury and NMDA-induced excitotoxicity.
Insights
Platelet-derived growth factor receptor-beta (PDGFR-beta) in neurons protects the brain from injury. Deleting PDGFR-beta in CNS neurons exacerbates damage from cryogenic injury and NMDA excitotoxicity.
Area of Science:
- Neuroscience
- Cell Biology
- Genetics
Background:
- Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) are present in the central nervous system (CNS), but their roles are not fully understood.
- Complete gene knockouts for PDGFRs are lethal, limiting research into their specific functions.
Purpose of the Study:
- To investigate the function of Platelet-derived growth factor receptor-beta (PDGFR-beta) in CNS neurons, particularly during the post-natal developmental stage.
- To elucidate the neuroprotective role of PDGFR-beta against brain injury.
Main Methods:
- Development of novel mutant mice with genetic deletion of PDGFR-beta specifically in CNS neurons.
- Immunohistochemical analysis to assess PDGFR-beta distribution in wild-type and mutant brains.
- Evaluation of cerebral damage following cryogenic injury and NMDA injection in mutant and control mice.
- TUNEL staining to quantify neuronal cell death.
Main Results:
- Mutant mice lacking neuronal PDGFR-beta survived to adulthood with no apparent anatomical defects.
- PDGFR-beta was significantly depleted in neurons and subventricular zone cells of mutant brains, while vascular PDGFR-beta remained unchanged.
- Mutant mice exhibited exacerbated cerebral damage after cryogenic injury and NMDA-induced excitotoxicity, with increased neuronal cell death and lesion formation.
- NMDA receptor expression levels were not altered in the mutant mice.
Conclusions:
- Neuronal PDGFR-beta plays a critical role in protecting CNS neurons from cryogenic injury.
- PDGFR-beta expressed in neurons confers protection against NMDA-induced excitotoxicity.
- Targeting neuronal PDGFR-beta may offer therapeutic potential for neuroprotection.
