Abstract
Insulin is known to act in the central nervous system to regulate several physiological and behavioural outcomes, including energy balance, glucose homeostasis and cognitive functioning. However, the neuronal populations through which insulin enhances cognitive performance remain unidentified. Insulin receptors are found in neuropeptide-Y (NPY) expressing neurons, which are abundant in the hypothalamus and hippocampus; regions involved in feeding behaviour and spatial memory, respectively. Here we show that mice with a tissue specific knockout of insulin receptors in NPY expressing neurons (IRlox/lox; NPYCre/+) display an impaired performance in the probe trial of the Morris Water Maze compared with control mice at both the 6 and the 12, but not at the 24 months time point, consistent with a crucial role of insulin and NPY in cognitive functioning. By 24 months of age all groups demonstrated similar reductions in spatial memory performance. Together, these data suggest that the mechanisms through which insulin influences cognitive functioning are, at least in part, via insulin receptor signaling in NPY expressing neurons. These results also highlight that cognitive impairments observed in aging may be due to impaired insulin signaling.
Highlights
Insulin signaling occurs when insulin activates the insulin receptor (IR), this results in glucose uptake by the cell
We examined Phosphorylated Akt (p-Akt) as a measure of insulin signaling in our knockout IRlox/lox;NPYCre/+ mouse model
To support our Morris Water Maze (MWM) data, we identified that IRlox/lox;NPYCre/+ mice exhibit reduced p-Akt in the dentate gyrus of the hippocampus at 6 months of age, suggesting that these mice exhibit downregulated intra-hippocampal IR signaling
Summary
Insulin signaling occurs when insulin activates the insulin receptor (IR), this results in glucose uptake by the cell. When insulin signaling becomes dysregulated, such as in the case of insulin resistance and longterm compensatory elevations of circulating insulin, an increased risk for developing cognitive pathologies occur, such as Alzheimer’s disease [2]. Animals that present with insulin resistance have reduced performance in the MWM [4,5,6,7,8,9,10,11,12]. These deficits can be ameliorated by central insulin infusion, which can increase performance in the memory component of the MWM [13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
