Abstract
Insulin-like growth factor I (IGF-I), a 70 aminoacid-long polypeptide with several metabolic and proliferative actions, is expressed in the rat brain during development and after acute injury [1–3]. The neuroprotective effect of IGF-I has been recently demonstrated in vitro using differentiated PC 12 cells undergoing apoptosis [4], cerebellar granules cultured in the presence of low K+ concentrations [5], and primary rat hippocampal neurons [6]. Moreover, there is a growing body of evidence showing that IGF-I injected intracerebroventricularly (icv) is neuroprotective in several experimental models of acute neuronal injury [7–8]. This suggests a possible therapeutic use for this trophic factor in peripheral or central nerve injuries. Some of the biological effects of IGF-I are probably mediated by des(1–3)IGF-I, an IGF-I derivative lacking the N-terminal tripeptide glycine-proline-glutamate (GPE). Des(1–3)IGF-I has been detected in the human brain (among other tissues) and is generally more potent than IGF-I in several in vitro assays [9–12]. The recent observation of Guan et al. that des(l-3)IGF-I is less effective then recombinant human IGF-I (rhIGF-I) as a neuronal rescue agent suggests that the central effects of this growth factor might be partially mediated by the N-terminal tripeptide GPE [13]. GPE (10-5 M) exhibits in vitro mitogenic properties on glial cells [14], modifies gonadotropin releasing hormone in response to N-methyl-d-aspartate (NMDA) receptor agonists [15–16] and potentiates K+-induced dopamine release from rat striatal slices [17]. All these effects probably involve NMDA receptor-mediated events, since they can be reverted by specific NMDA receptor antagonists.
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© 1998 Springer-Verlag Italia, Milano
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Curatolo, L., Raimondi, G.L., Caccia, C., Wong, E., Gatti, S., Post, C. (1998). Neuroprotective Effect of GPE Pretreatment on Rat Hippocampal Organotypic Cultures Exposed to NMDA. In: Müller, E.E. (eds) IGFs in the Nervous System. Springer, Milano. https://doi.org/10.1007/978-88-470-2246-1_13
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DOI: https://doi.org/10.1007/978-88-470-2246-1_13
Publisher Name: Springer, Milano
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