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Brain Res Dev Brain Res. 1997 Apr 18;99(2):234-42.

Insulin-like growth factor I (IGF-I) is a critical trophic factor for developing cerebellar granule cells.

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  • 1Department of Pharmacology, University of Maryland School of Medicine, Baltimore 21201, USA.


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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