RGD Reference Report - Activation of glycogen synthase kinase 3 beta (GSK-3beta) by platelet activating factor mediates migration and cell death in cerebellar granule neurons. - Rat Genome Database

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Activation of glycogen synthase kinase 3 beta (GSK-3beta) by platelet activating factor mediates migration and cell death in cerebellar granule neurons.

Authors: Tong, N  Sanchez, JF  Maggirwar, SB  Ramirez, SH  Guo, H  Dewhurst, S  Gelbard, HA 
Citation: Tong N, etal., Eur J Neurosci. 2001 May;13(10):1913-22.
RGD ID: 10045651
Pubmed: PMID:11403684   (View Abstract at PubMed)

Children with vertically acquired HIV-1 can present with a rapidly progressive encephalopathy and neuronal apoptosis in the first 12-18 months of life. Furthermore, abnormal prenatal platelet activating factor (PAF) signalling may result in lissencephaly, a disorder of neuronal migration. PAF, produced from human immunodeficiency virus type 1 (HIV-1) -infected brain-resident macrophages, induces neuronal apoptosis in cultured cerebellar granule neurons (CGNs) in part by activating glycogen synthase kinase 3 beta (GSK-3beta). However, PAF can also inhibit migration of CGNs that are dispersed and allowed to reaggregate. Therefore, we investigated the biological effects following activation of GSK-3beta by PAF, and whether these effects were dependent on the culture conditions of the CGNs. We show here that activation of neuronal GSK-3beta by PAF is receptor-specific, with similar kinetics of activation in both monolayer cultures of CGNs that have ceased to migrate and reaggregate cultures of CGNs that are actively migrating. However, PAF receptor activation in reaggregated CGNs inhibits neuronal migration and induces approximately half the level of neuronal apoptosis compared with PAF-treated CGN cultures that have ceased to migrate. PAF-mediated inhibition of neuronal migration in reaggregated CGNs or induction of apoptosis in CGNs that have ceased to migrate can be reversed by either PAF receptor antagonists, or the GSK-3beta inhibitors lithium or valproic acid, in a dose-dependent manner. Abnormal PAF signalling that results in GSK-3beta overactivation may represent a common mechanism for pathological defects in neuronal migration in the prenatal period and neuronal apoptosis in the postnatal period.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of neuron migration  IMP 10045651 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gsk3b  (glycogen synthase kinase 3 beta)


Additional Information