Effects of acute and chronic administration of GIP analogues on cognition, synaptic plasticity and neurogenesis in mice

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Effects of acute and chronic administration of GIP analogues on cognition, synaptic plasticity and neurogenesis in mice. / Faivre, Emilie; Hamilton, Alison; Hölscher, Christian.
In: European Journal of Pharmacology, Vol. 674, No. 2-3, 15.01.2012, p. 294-306.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Bibtex

@article{fdf0d7ea31f94d55b0d1797c1328a6eb,

title = "Effects of acute and chronic administration of GIP analogues on cognition, synaptic plasticity and neurogenesis in mice",

abstract = "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 250 nmol/kg i.p.). In memory tests, no change was observed, whilst (Pro3)GIP at 25 nmol/kg i.p. impaired memory formation. In a chronic study over 4 weeks, mice injected with D-Ala2GIP (2.5 or 25 nmol/kg i.p.) and (Pro3)GIP (25 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.",

keywords = "Animals, CA1 Region, Hippocampal, Cell Proliferation, Cognition, Dentate Gyrus, Exploratory Behavior, Gastric Inhibitory Polypeptide, Long-Term Potentiation, Male, Memory, Mice, Mice, Inbred C57BL, Motor Activity, Neural Stem Cells, Neurogenesis, Neuronal Plasticity, Receptors, Gastrointestinal Hormone, Synapses, Time Factors",

author = "Emilie Faivre and Alison Hamilton and Christian H{\"o}lscher",

year = "2012",

month = jan,

day = "15",

doi = "10.1016/j.ejphar.2011.11.007",

language = "English",

volume = "674",

pages = "294--306",

journal = "European Journal of Pharmacology",

issn = "0014-2999",

publisher = "Elsevier",

number = "2-3",

}

RIS

TY - JOUR

T1 - Effects of acute and chronic administration of GIP analogues on cognition, synaptic plasticity and neurogenesis in mice

AU - Faivre, Emilie

AU - Hamilton, Alison

AU - Hölscher, Christian

PY - 2012/1/15

Y1 - 2012/1/15

N2 - 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 250 nmol/kg i.p.). In memory tests, no change was observed, whilst (Pro3)GIP at 25 nmol/kg i.p. impaired memory formation. In a chronic study over 4 weeks, mice injected with D-Ala2GIP (2.5 or 25 nmol/kg i.p.) and (Pro3)GIP (25 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.

AB - 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 250 nmol/kg i.p.). In memory tests, no change was observed, whilst (Pro3)GIP at 25 nmol/kg i.p. impaired memory formation. In a chronic study over 4 weeks, mice injected with D-Ala2GIP (2.5 or 25 nmol/kg i.p.) and (Pro3)GIP (25 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.

KW - Animals

KW - CA1 Region, Hippocampal

KW - Cell Proliferation

KW - Cognition

KW - Dentate Gyrus

KW - Exploratory Behavior

KW - Gastric Inhibitory Polypeptide

KW - Long-Term Potentiation

KW - Male

KW - Memory

KW - Mice

KW - Mice, Inbred C57BL

KW - Motor Activity

KW - Neural Stem Cells

KW - Neurogenesis

KW - Neuronal Plasticity

KW - Receptors, Gastrointestinal Hormone

KW - Synapses

KW - Time Factors

U2 - 10.1016/j.ejphar.2011.11.007

DO - 10.1016/j.ejphar.2011.11.007

M3 - Journal article

C2 - 22115896

VL - 674

SP - 294

EP - 306

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 2-3

ER -

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