D-êµ-hydroxybutyrate stabilizes hippocampal CA3-CA1 circuit during acute insulin resistance.
PNAS Nexus
; 3(5): pgae196, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38818236
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-êµ-hydroxybutyrate (D-êµHb) on mouse brain metabolism during acute insulin resistance (AIR). We found that both AIR and D-êµHb 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-êµHb rescued neuronal functions associated with axonal conduction, synchronization, and LTP.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
PNAS Nexus
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos