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.
Keywords: Apoptosis, development, gene expression, neuropeptide, neurotrophic effect
Central Nervous System Agents in Medicinal Chemistry
Title: Gastric Inhibitory Polypeptide and its Receptor are Expressed in the Central Nervous System and Support Neuronal Survival
Volume: 11 Issue: 3
Author(s): Sabrina Paratore, Maria Teresa Ciotti, Magali Basille, David Vaudry, Antonietta Gentile, Rosalba Parenti, Pietro Calissano and Sebastiano Cavallaro
Affiliation:
Keywords: Apoptosis, development, gene expression, neuropeptide, neurotrophic effect
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.
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Paratore Sabrina, Teresa Ciotti Maria, Basille Magali, Vaudry David, Gentile Antonietta, Parenti Rosalba, Calissano Pietro and Cavallaro Sebastiano, Gastric Inhibitory Polypeptide and its Receptor are Expressed in the Central Nervous System and Support Neuronal Survival, Central Nervous System Agents in Medicinal Chemistry 2011; 11 (3) . https://dx.doi.org/10.2174/187152411798047771
DOI https://dx.doi.org/10.2174/187152411798047771 |
Print ISSN 1871-5249 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6166 |
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