Central Nervous System Agents in Medicinal Chemistry 2011-09-01

Gastric inhibitory polypeptide and its receptor are expressed in the central nervous system and support neuronal survival.

Sabrina Paratore, Maria Teresa Ciotti, Magali Basille, David Vaudry, Antonietta Gentile, Rosalba Parenti, Pietro Calissano, Sebastiano Cavallaro

Index: Cent. Nerv. Syst. Agents Med. Chem. 11 , 210-222, (2011)

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Abstract

The development of neuronal apoptosis depends on an intrinsic transcriptional program. By DNA microarray technology, we have previously implicated a number of genes in different paradigms of neuronal apoptosis. In the present study, we investigated the spatiotemporal pattern of expression of two of these genes, gastric inhibitory polypeptide (Gip) and its receptor (Gipr) in the rat central nervous system. The levels of their transcripts were measured with real-time quantitative polymerase chain reaction and in situ-hybridization. Widespread expression of Gip and Gipr was found in adult rat brain, whereas during postnatal cerebellum development, they were highly expressed in the external and internal granule layer, and in Purkinje cells. To investigate the possible biological function of Gip we examined its effects in vitro. Addition of Gip to cultured cerebellar granule neurons reduced the extent of apoptotic death induced by switching the growing medium from 25 to 5 mM K+. This neurotrophic effect was mimicked by that of PACAP38 and IGF1. We conclude that Gip acts as an endogenous neurotrophic factor and supports neuronal survival.