Genetic Ablation of PLA2G6 in Mice Leads to Cerebellar Atrophy Characterized by Purkinje Cell Loss and Glial Cell Activation

Hdl Handle:
http://hdl.handle.net/10675.2/681
Title:
Genetic Ablation of PLA2G6 in Mice Leads to Cerebellar Atrophy Characterized by Purkinje Cell Loss and Glial Cell Activation
Authors:
Zhao, Zhengshan; Wang, Jing; Zhao, Chunying; Bi, Weina; Yue, Zhenyu; Ma, Zhongmin Alex
Abstract:
Infantile neuroaxonal dystrophy (INAD) is a progressive, autosomal recessive neurodegenerative disease characterized by axonal dystrophy, abnormal iron deposition and cerebellar atrophy. This disease was recently mapped to PLA2G6, which encodes group VI Ca2+-independent phospholipase A2 (iPLA2 or iPLA2b). Here we show that genetic ablation of PLA2G6 in mice (iPLA2b-/-) leads to the development of cerebellar atrophy by the age of 13 months. Atrophied cerebella exhibited significant loss of Purkinje cells, as well as reactive astrogliosis, the activation of microglial cells, and the pronounced upregulation of the pro-inflammatory cytokines tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b). Moreover, glial cell activation and the elevation in TNF-a and IL-1b expression occurred before apparent cerebellar atrophy. Our findings indicate that the absence of PLA2G6 causes neuroinflammation and Purkinje cell loss and ultimately leads to cerebellar atrophy. Our study suggests that iPLA2b-/- mice are a valuable model for cerebellar atrophy in INAD and that early antiinflammatory therapy may help slow the progression of cerebellar atrophy in this deadly neurodegenerative disease.
Editors:
Mei, Lin
Citation:
PLoS One. 2011 Oct 28; 6(10):e26991
Issue Date:
28-Oct-2011
URI:
http://hdl.handle.net/10675.2/681
DOI:
10.1371/journal.pone.0026991
PubMed ID:
22046428
PubMed Central ID:
PMC3203935
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Neurology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorZhao, Zhengshanen_US
dc.contributor.authorWang, Jingen_US
dc.contributor.authorZhao, Chunyingen_US
dc.contributor.authorBi, Weinaen_US
dc.contributor.authorYue, Zhenyuen_US
dc.contributor.authorMa, Zhongmin Alexen_US
dc.contributor.editorMei, Lin-
dc.date.accessioned2012-10-26T16:29:32Z-
dc.date.available2012-10-26T16:29:32Z-
dc.date.issued2011-10-28en_US
dc.identifier.citationPLoS One. 2011 Oct 28; 6(10):e26991en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid22046428en_US
dc.identifier.doi10.1371/journal.pone.0026991en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/681-
dc.description.abstractInfantile neuroaxonal dystrophy (INAD) is a progressive, autosomal recessive neurodegenerative disease characterized by axonal dystrophy, abnormal iron deposition and cerebellar atrophy. This disease was recently mapped to PLA2G6, which encodes group VI Ca2+-independent phospholipase A2 (iPLA2 or iPLA2b). Here we show that genetic ablation of PLA2G6 in mice (iPLA2b-/-) leads to the development of cerebellar atrophy by the age of 13 months. Atrophied cerebella exhibited significant loss of Purkinje cells, as well as reactive astrogliosis, the activation of microglial cells, and the pronounced upregulation of the pro-inflammatory cytokines tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b). Moreover, glial cell activation and the elevation in TNF-a and IL-1b expression occurred before apparent cerebellar atrophy. Our findings indicate that the absence of PLA2G6 causes neuroinflammation and Purkinje cell loss and ultimately leads to cerebellar atrophy. Our study suggests that iPLA2b-/- mice are a valuable model for cerebellar atrophy in INAD and that early antiinflammatory therapy may help slow the progression of cerebellar atrophy in this deadly neurodegenerative disease.en_US
dc.rightsZhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectModel Organismsen_US
dc.subjectAnimal Modelsen_US
dc.subjectMouseen_US
dc.subjectNeuroscienceen_US
dc.subjectDevelopmental Neuroscienceen_US
dc.subjectMolecular Neuroscienceen_US
dc.subjectMedicineen_US
dc.subjectClinical Geneticsen_US
dc.subjectAutosomal Recessiveen_US
dc.subjectClinical Immunologyen_US
dc.subjectImmune Systemen_US
dc.subjectCytokinesen_US
dc.subjectDiagnostic Medicineen_US
dc.subjectPathologyen_US
dc.subjectAnatomical Pathologyen_US
dc.subjectNeuropathologyen_US
dc.subjectNeurologyen_US
dc.subjectCerebellar Disordersen_US
dc.subjectNeurodegenerative Diseasesen_US
dc.subjectPediatricsen_US
dc.subjectDevelopmental and Pediatric Neurologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAtrophyen_US
dc.subject.meshCerebellar Diseasesen_US
dc.subject.meshGroup VI Phospholipases A2en_US
dc.subject.meshInterleukin-1betaen_US
dc.subject.meshMiceen_US
dc.subject.meshMicrogliaen_US
dc.subject.meshNeuroaxonal Dystrophiesen_US
dc.subject.meshNeurogliaen_US
dc.subject.meshPurkinje Cellsen_US
dc.subject.meshTumor Necrosis Factor-alphaen_US
dc.titleGenetic Ablation of PLA2G6 in Mice Leads to Cerebellar Atrophy Characterized by Purkinje Cell Loss and Glial Cell Activationen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3203935en_US
dc.contributor.corporatenameDepartment of Neurology-

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