Linked Life Data

20596079

Source:http://linkedlifedata.com/resource/pubmed/id/20596079

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-12-14
pubmed:abstractText
IGF1, an anabolic and neuroprotective factor, promotes neuronal survival by blocking apoptosis. It is released into the bloodstream by the liver, or synthesized locally by muscles and neural cells, acting in an autocrine or paracrine fashion. Intriguingly, genetic studies conducted in invertebrate and murine models also suggest that an excess of IGF1 signaling may trigger neurodegeneration. This emphasizes the importance of gaining a better understanding of the mechanisms controlling IGF1 regulation and gene transcription. In the cerebellum, Igf1 expression is activated just before birth in a subset of Purkinje cells (PCs). Mice carrying a null mutation for HLH transcription factor EBF2 feature PC apoptosis at birth. We show that Igf1 is sharply downregulated in Ebf2 null PCs starting before the onset of PC death. In vitro, EBF2 binds a conserved distal Igf1 promoter region. The pro-survival PI3K signaling pathway is strongly inhibited in mutant cerebella. Finally, Ebf2 null organotypic cultures respond to IGF1 treatment by inhibiting PC apoptosis. Consistently, wild type slices treated with an IGF1 competitor feature a sharp increase in PC death. Our findings reveal that IGF1 is required for PC survival in the neonatal cerebellum, and identify a new mechanism regulating its local production in the CNS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1476-5403
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
48-59
pubmed:meshHeading
pubmed-meshheading:20596079-Animals, pubmed-meshheading:20596079-Animals, Newborn, pubmed-meshheading:20596079-Apoptosis, pubmed-meshheading:20596079-Basic Helix-Loop-Helix Transcription Factors, pubmed-meshheading:20596079-Cell Survival, pubmed-meshheading:20596079-Cells, Cultured, pubmed-meshheading:20596079-Cerebellum, pubmed-meshheading:20596079-Insulin-Like Growth Factor I, pubmed-meshheading:20596079-Male, pubmed-meshheading:20596079-Mice, pubmed-meshheading:20596079-Mice, Inbred C57BL, pubmed-meshheading:20596079-Phosphatidylinositol 3-Kinases, pubmed-meshheading:20596079-Promoter Regions, Genetic, pubmed-meshheading:20596079-Purkinje Cells, pubmed-meshheading:20596079-RNA, Small Interfering, pubmed-meshheading:20596079-RNA Interference, pubmed-meshheading:20596079-Signal Transduction
pubmed:year
2011
pubmed:articleTitle
Local insulin-like growth factor I expression is essential for Purkinje neuron survival at birth.
pubmed:affiliation
Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't