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

Authors

Bartosz Kula, Del Monte Institute for Neuroscience, Department of Neuroscience, University of Rochester, School of Medicine and Dentistry, Rochester, USA.
Botond Antal, Department of Biomedical Engineering, Stony Brook University, Stony Brook, USA.
Corey Weistuch, Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Florian Gackiere, Neuroservices Alliance, Les Jardins de l'Entreprise, Quartier de le Confrerie, Le Puy Ste Reparade, France.
Alexander Barre, Neuroservices Alliance, Les Jardins de l'Entreprise, Quartier de le Confrerie, Le Puy Ste Reparade, France.
Victor Velado, Center for Neuroscience Research, Children's National Research Institute, Children's National Hospital, Washington D.C., USA.
Jeffrey M. Hubbard, Neuroservices Alliance, Les Jardins de l'Entreprise, Quartier de le Confrerie, Le Puy Ste Reparade, France.
Maria Kukley, Achucarro Basque Center for Neuroscience, Leioa, Spain.
Lilianne R. Mujica-Parodi, Department of Biomedical Engineering, Stony Brook University, Stony Brook, USA.
Nathan A. Smith, Del Monte Institute for Neuroscience, Department of Neuroscience, University of Rochester, School of Medicine and Dentistry, Rochester, USA.

Document Type

Journal Article

Publication Date

1-12-2024

Journal

bioRxiv : the preprint server for biology

DOI

10.1101/2023.08.23.554428

Keywords

GLUT4; beta-hydroxybutyrate; hippocampus; insulin resistance; ketone bodies

Abstract

1.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-P-hydroxybutyrate (D-βHb) on mouse brain metabolism during acute insulin resistance (AIR). We found that both AIR and D-βHb had distinct impacts across neuronal compartments: AIR decreased synaptic activity and long-term potentiation (LTP) and impaired axonal conduction, synchronization, and action potential (AP) properties, while D- PHb rescued neuronal functions associated with axonal conduction, synchronization and LTP.

APA Citation

Kula, Bartosz; Antal, Botond; Weistuch, Corey; Gackiere, Florian; Barre, Alexander; Velado, Victor; Hubbard, Jeffrey M.; Kukley, Maria; Mujica-Parodi, Lilianne R.; and Smith, Nathan A., "D-β-hydroxybutyrate stabilizes hippocampal CA3-CA1 circuit during acute insulin resistance" (2024). GW Authored Works. Paper 4185.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4185

Department

Pediatrics