D-ꞵ-hydroxybutyrate stabilizes hippocampal CA3-CA1 circuit during acute insulin resistance

Author:

Kula Bartosz1ORCID,Antal Botond23,Weistuch Corey4ORCID,Gackière Florian5ORCID,Barre Alexander5,Velado Victor6,Hubbard Jeffrey M5ORCID,Kukley Maria78,Mujica-Parodi Lilianne R239ORCID,Smith Nathan A1610ORCID

Affiliation:

1. Del Monte Institute for Neuroscience, Department of Neuroscience, University of Rochester, School of Medicine and Dentistry , Rochester, NY 14642 , USA

2. Department of Biomedical Engineering, Stony Brook University , Stony Brook, NY 11794 , USA

3. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02129 , USA

4. Department of Medical Physics, Memorial Sloan Kettering Cancer Center , New York, NY 10065 , USA

5. Neuroservices Alliance, Les Jardins de l’Entreprise , Quartier de le Confrérie, 13610 Le Puy-Sainte-Réparade , France

6. Center for Neuroscience Research, Children’s National Research Institute, Children’s National Hospital , Washington, DC 20012 , USA

7. Achucarro Basque Center for Neuroscience , 48940 Leioa, Bizkaia , Spain

8. Ikerbasque—Basque Foundation for Science , 48009 Bilbao , Spain

9. Laufer Center for Physical and Quantitative Biology, Stony Brook University , Stony Brook, NY 11794 , USA

10. School of Medicine and Health Sciences, George Washington University , Washington, DC 20052 , USA

Abstract

Abstract The brain primarily relies on glycolysis for mitochondrial respiration but switches to alternative fuels such as ketone bodies (KBs) when less glucose is available. Neuronal KB uptake, which does not rely on glucose transporter 4 (GLUT4) or insulin, has shown promising clinical applicability in alleviating the neurological and cognitive effects of disorders with hypometabolic components. However, the specific mechanisms by which such interventions affect neuronal functions are poorly understood. In this study, we pharmacologically blocked GLUT4 to investigate the effects of exogenous KB D-ꞵ-hydroxybutyrate (D-ꞵHb) on mouse brain metabolism during acute insulin resistance (AIR). We found that both AIR and D-ꞵHb had distinct impacts across neuronal compartments: AIR decreased synaptic activity and long-term potentiation (LTP) and impaired axonal conduction, synchronization, and action potential properties, while D-ꞵHb rescued neuronal functions associated with axonal conduction, synchronization, and LTP.

Funder

National Institutes of Health

National Science Foundation

Department of Defense

Publisher

Oxford University Press (OUP)

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3