Neuroprotective Effect of GPE Pretreatment on Rat Hippocampal Organotypic Cultures Exposed to NMDA

  • L. Curatolo
  • G. L. Raimondi
  • C. Caccia
  • E. Wong
  • S. Gatti
  • C. Post


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.


Neuroprotective Effect Organotypic Culture Hippocampal Organotypic Culture Induce Dopamine Release Acute Neuronal Injury 
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Copyright information

© Springer-Verlag Italia, Milano 1998

Authors and Affiliations

  • L. Curatolo
    • 1
  • G. L. Raimondi
    • 1
  • C. Caccia
    • 1
  • E. Wong
    • 1
  • S. Gatti
    • 1
  • C. Post
    • 1
  1. 1.CNS Research BiologyPharmacia & UpjohnNerviano (MI)Italy

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