GSK-3ß inhibitor, AR-A014418 attenuates insulin resistance induced cognitive deficit in mice

Abstract

Event Abstract Back to Event GSK-3ß inhibitor, AR-A014418 attenuates insulin resistance induced cognitive deficit in mice Sorabh Sharma1* and Rajeev Taliyan1 1 Birla Institute of Technology and Science, Pilani, Department of Pharmacy, India Numerous epidemiological studies have demonstrated that insulin resistance contributes to Alzheimer’s disease (AD) pathogenesis. However the molecular mechanisms of association between these still remain elusive. Among the various possible mechanisms, the GSK-3ß activity has been reported to be elevated in insulin-resistance, type 2 diabetes and AD. Thus, the present study was designed to explore the neuroprotective role of GSK-3ß inhibitor, AR-A014418 in insulin resistance induced cognitive impairment. Further, we have explored the possible molecular mechanisms involved in cognitive impairment associated with insulin resistance. The mice subjected to high fat diet (HFD) exhibited characteristic features of insulin resistance viz. increased serum glucose, triglycerides, cholesterol, insulin levels and impaired spatial learning and memory ability along with elevated oxidative stress and neuro-inflammatory markers. The observed changes occurred concurrently with reduced brain derived neurotrophic factor (BDNF). In contrast, the mice treated with AR-A014418 showed a significant reduction in plasma glucose, triglycerides, cholesterol, insulin levels and improvement in learning and memory performance. Moreover, AR- A014418 dose dependently augment the BDNF levels in HFD fed mice. Based upon these findings it could be suggested that GSK-3ß inhibition could prove to be beneficial in insulin resistance induced cognitive deficit and this neuroprotection could be the result of enhanced BDNF based synaptic plasticity. Keywords: Cognition, in vivo, Neuroinflammation, GSK-3ß activity, Insulin Resistance Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: O02: Postgraduate Travel Awardees Oral Session 2 Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Sharma S and Taliyan R (2016). GSK-3ß inhibitor, AR-A014418 attenuates insulin resistance induced cognitive deficit in mice. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00083 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Mr. Sorabh Sharma, Birla Institute of Technology and Science, Pilani, Department of Pharmacy, Pilani, Rajasthan, India, sharmasorabh88@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sorabh Sharma Rajeev Taliyan Google Sorabh Sharma Rajeev Taliyan Google Scholar Sorabh Sharma Rajeev Taliyan PubMed Sorabh Sharma Rajeev Taliyan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.