High-Salt Diet Increases Suprachiasmatic Neuronal Excitability Through Endothelin Receptor Type B Signaling

Area of Science:

• Neuroscience
• Chronobiology
• Physiology

Background:

• Circadian rhythms regulate daily biological processes, including blood pressure and sodium excretion.
• The Endothelin B (ETB) receptor is implicated in peripheral circadian clock function and sodium regulation, particularly with high-salt diets.
• The role of ETB receptors in the suprachiasmatic nucleus (SCN), the brain's master circadian pacemaker, remains largely unexplored, despite their presence in SCN astrocytes.

Purpose of the Study:

• To investigate the impact of a high-salt diet on the circadian system via the ETB receptor.
• To examine behavioral, molecular, and physiological effects of high-salt intake on circadian rhythms in mice.
• To elucidate the role of ETB signaling in the SCN's response to dietary sodium.

Main Methods:

• C57BL/6 mice were fed a high-salt diet (4.0% NaCl) for two weeks.
• Wheel-running activity was monitored to assess behavioral changes.
• Fluorescence in situ hybridization and loose-patch electrophysiology were used to analyze SCN ETB mRNA expression and neuronal excitability.
• Ex vivo experiments involved applying ETB antagonists and endothelin-3, with and without NMDA receptor antagonists.

Main Results:

• High-salt diet altered nighttime wheel-running activity patterns.
• SCN ETB mRNA expression and neuronal excitability increased at night in mice on a high-salt diet.
• ETB receptor antagonism ameliorated high-salt diet-induced SCN hyperactivity, while endothelin-3 mimicked these effects.
• Endothelin-3's excitatory effects were blocked by an NMDA receptor antagonist, indicating glutamate mediation.

Conclusions:

• Functional ETB receptors are present in SCN astrocytes.
• Endothelin signaling plays a novel role in mediating the SCN's neuronal response to dietary sodium intake.
• Dietary salt intake can influence circadian rhythmicity through the ETB receptor pathway in the SCN.