Insulin-like growth factor I (IGF-I) is a critical trophic factor for developing cerebellar granule cells.
In this study we showed that insulin-like growth factor I (IGF-I) directly increased cell survival in pure cerebellar granule cell cultures established from postnatal day 7 (P7) mice. The maximal survival-promoting effect could be obtained at low IGF-I concentrations (3-5 ng/ml). Withdrawal of IGF-I from differentiated granule neurons resulted in neuronal death which suggests that IGF-I has a survival-promoting effect on differentiated granule neurons. Furthermore, the survival-promoting effect of IGF-I was not attenuated by the addition of K252a, a selective blocker of Trk signaling, indicating that the survival-promoting effect of IGF-I did not require or was not mediated by endogenously produced neurotrophins, such as BDNF and NT3. Further experiments also suggest that IGF-I stimulates proliferation of granule cell precursors and allows terminal granule neuron differentiation to occur, as indicated by the expression of terminal differentiation markers MEF2A and GABA(A) alpha6. Thus, IGF-I could potentially function as both a mitogen and a trophic factor for developing granule cells. This dual action of IGF-I may be important in regulating granule neuron number.
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Department of Pharmacology, University of Maryland School of Medicine, Baltimore 21201, USA.
Bulleit
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D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D003102:Colloids; D053938:DNA Fragmentation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D064326:MEF2 Transcription Factors; D051379:Mice; D008815:Mice, Inbred Strains; D018006:Myogenic Regulatory Factors; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D011205:Povidone; D012333:RNA, Messenger / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics; D012822:Silicon Dioxide; D013936:Thymidine / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics; D014316:Tritium
D015415:Biomarkers; D003102:Colloids; D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; C578036:Mef2a protein, mouse; D018006:Myogenic Regulatory Factors; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D014157:Transcription Factors; D014316:Tritium; C016039:Percoll; D007334:Insulin-Like Growth Factor I; D012822:Silicon Dioxide; D011205:Povidone; D013936:Thymidine