title: Effects of glucose-dependent insulinotropic polypeptide receptor knockout and a high-fat diet on cognitive function and hippocampal gene expression in mice.
abstract: It has been previously demonstrated that compromise of glucose-dependent insulinotropic polypeptide receptor (GIPR) action and chronic consumption of a high-fat diet can independently impair memory and learning ability, however, the underlying pathology remain to be elucidated. The present study investigated the effects of GIPR knockout (KO), alone and in combination with a high-fat diet, on aspects of cognitive function and hippocampal gene expression in mice. In object recognition tests, normal mice exhibited effective memory, preferring to investigate the novel over the familiar object. However, wild-type (WT) mice fed a high-fat diet and GIPR KO mice fed a standard or high-fat diet demonstrated no such discrimination, suggesting the impairment of memory function. This decline in cognitive function was associated with marked changes in the expression levels of hippocampal genes involved in memory and learning. The chronic consumption of a high-fat diet decreased the hippocampal gene expression levels of mammalian target of rapamycin (mTOR), neurotrophic tyrosine kinase receptor type 2 (NTRK2) and synaptophysin. Notably, the GIPR KO mice fed a high-fat diet exhibited no reduction in the hippocampal expression of synaptophysin expression, however, the GIPR KO mice fed a standard rodent maintenance diet exhibited reduced hippocampal expression of mTOR compared with the WT controls. These data highlighted the importance of intact GIPR signalling and dietary composition in modulating memory and learning, and hippocampal pathways involved in the maintenance of synaptic plasticity, including mTOR and NTRK2, appear to be key in this regard.
authors.affiliation: School of Biomedical Sciences, The SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Londonderry BT52 1SA, Northern Ireland, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Lennox
authors.forename: Rachael R
authors.initials: RR
authors.lastname: Lennox
authors.affiliation: School of Biomedical Sciences, The SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Londonderry BT52 1SA, Northern Ireland, UK.
authors.forename: R Charlotte
authors.initials: RC
authors.lastname: Moffett
authors.forename: Charlotte
authors.initials: C
authors.lastname: Moffett
authors.affiliation: School of Biomedical Sciences, The SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Londonderry BT52 1SA, Northern Ireland, UK.
authors.forename: David W
authors.initials: DW
authors.lastname: Porter
authors.affiliation: School of Biomedical Sciences, The SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Londonderry BT52 1SA, Northern Ireland, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Irwin
authors.affiliation: School of Biomedical Sciences, The SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Londonderry BT52 1SA, Northern Ireland, UK.
authors.forename: Victor A
authors.initials: VA
authors.lastname: Gault
authors.affiliation: School of Biomedical Sciences, The SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Londonderry BT52 1SA, Northern Ireland, UK.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
mesh_terms: D000818:Animals; D003071:Cognition / Q000502:physiology*; D059305:Diet, High-Fat; D015870:Gene Expression / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007858:Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
chemical_list: D007328:Insulin; D011964:Receptors, Gastrointestinal Hormone; C041086:gastric inhibitory polypeptide receptor