کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5829862 | 1559007 | 2012 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Effects of acute and chronic administration of GIP analogues on cognition, synaptic plasticity and neurogenesis in mice
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
Type 2 diabetes is a risk factor for Alzheimer's disease. Insulin receptor desensitisation has been found in Alzheimer brains, which may be the underlying link. Glucose-dependent insulinotropic polypeptide (GIP), an incretin hormone, normalises insulin signalling in diabetes. GIP and the GIP receptors are widely expressed in the brain, and GIP has been shown to have growth factor and neuroprotective properties. Here we investigate the potential therapeutic properties of different doses of the protease resistant long-lasting GIP receptor agonist D-Ala2GIP and the antagonist (Pro3)GIP in C57Bl/6 mice. We found that after acute injection, D-Ala2GIP had few effects on general behaviour in the open field at any dose tested (2.5, 25, 100, or 250Â nmol/kg i.p.). In memory tests, no change was observed, whilst (Pro3)GIP at 25Â nmol/kg i.p. impaired memory formation. In a chronic study over 4Â weeks, mice injected with D-Ala2GIP (2.5 or 25Â nmol/kg i.p.) and (Pro3)GIP (25Â nmol/kg i.p.) learned a water maze task and object recognition task without impairment. In LTP recording in area CA1, both (Pro3)GIP as well as D-Ala2GIP enhanced LTP formation. In addition, the proliferation of neuronal progenitor cells in the dentate gyrus was increased both by D-Ala2GIP and (Pro3)GIP. The results show that the antagonist (Pro3)GIP has agonistic effects in chronic use, and both (Pro3)GIP and the agonist D-Ala2GIP are safe to use in wt mice and induces no major behavioural side effects nor impairments in learning whilst enhancing LTP and neuronal progenitor cell proliferation, which may be useful in treating neurodegenerative diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 674, Issues 2â3, 15 January 2012, Pages 294-306
Journal: European Journal of Pharmacology - Volume 674, Issues 2â3, 15 January 2012, Pages 294-306
نویسندگان
Emilie Faivre, Alison Hamilton, Christian Hölscher,