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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain / anatomy & histology
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Brain / drug effects
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Brain / metabolism*
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Cell Survival / physiology*
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Cells, Cultured
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Cyclic AMP / metabolism
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Gastric Inhibitory Polypeptide / genetics
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Gastric Inhibitory Polypeptide / metabolism*
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Gastric Inhibitory Polypeptide / pharmacology
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Gene Expression
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Insulin-Like Growth Factor I / pharmacology
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Male
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Nerve Growth Factors / genetics
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Nerve Growth Factors / metabolism
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Nerve Growth Factors / pharmacology
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Neurons / cytology
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Neurons / drug effects
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Neurons / physiology*
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Neuroprotective Agents / metabolism
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Neuroprotective Agents / pharmacology
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Pituitary Adenylate Cyclase-Activating Polypeptide / pharmacology
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Rats
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Rats, Wistar
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Receptor, IGF Type 1 / genetics
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Receptor, IGF Type 1 / metabolism
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Receptors, Gastrointestinal Hormone / genetics
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Receptors, Gastrointestinal Hormone / metabolism*
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / genetics
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / metabolism
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Receptors, Vasoactive Intestinal Peptide, Type II / genetics
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Receptors, Vasoactive Intestinal Peptide, Type II / metabolism
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Receptors, Vasoactive Intestinal Polypeptide, Type I / genetics
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Receptors, Vasoactive Intestinal Polypeptide, Type I / metabolism
Substances
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Nerve Growth Factors
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Neuroprotective Agents
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Gastrointestinal Hormone
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
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Receptors, Vasoactive Intestinal Peptide, Type II
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Receptors, Vasoactive Intestinal Polypeptide, Type I
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Gastric Inhibitory Polypeptide
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Insulin-Like Growth Factor I
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gastric inhibitory polypeptide receptor
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Cyclic AMP
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Receptor, IGF Type 1