Neuroinflammation Contributes to High Salt Intake-Augmented Neuronal Activation and Active Coping Responses to Acute Stress

• Published in: The international journal of neuropsychopharmacology Vol. 22; no. 2; pp. 137 - 142
• Main Authors: Gilman, T Lee, Mitchell, Nathan C, Daws, Lynette C, Toney, Glenn M
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.02.2019
• Subjects: Adaptation, Psychological - drug effects; Animals; Anti-Inflammatory Agents - pharmacology; Basolateral Nuclear Complex - drug effects; Basolateral Nuclear Complex - immunology; Basolateral Nuclear Complex - metabolism; Behavior, Animal - drug effects; Brain - drug effects; Brain - immunology; Brain - physiopathology; Disease Models, Animal; Inflammation - complications; Inflammation - drug therapy; Male; Mice; Mice, Inbred C57BL; Microglia - drug effects; Microglia - immunology; Minocycline - pharmacology; Paraventricular Hypothalamic Nucleus - drug effects; Paraventricular Hypothalamic Nucleus - immunology; Paraventricular Hypothalamic Nucleus - metabolism; Rapid Communication; Sodium Chloride, Dietary - adverse effects; Stress, Psychological - drug therapy; Stress, Psychological - immunology; Stress, Psychological - physiopathology
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1093/ijnp/pyy099

High dietary salt intake increases risk of stress-related neuropsychiatric disorders. Here, we explored the contribution of high dietary salt intake-induced neuroinflammation in key stress-responsive brain regions, the hypothalamic paraventricular nucleus and basolateral amygdala, in promoting exaggerated neuronal activation and coping behaviors in response to acute psychogenic stress. Mice that underwent high dietary salt intake exhibited increased active stress coping behaviors during and after an acute swim stress, and these were reduced by concurrent administration of minocycline, an inhibitor of microglial activation, without affecting body fluid hyperosmolality caused by high dietary salt intake. Moreover, minocycline attenuated high dietary salt intake-induced increases of paraventricular nucleus tumor necrosis factor-α, activated microglia (ionized calcium-binding adaptor molecule 1), and acute swim stress-induced neuronal activation (c-Fos). In the basolateral amygdala, similar effects were observed on ionized calcium-binding adaptor molecule 1+ and c-Fos+ counts, but not tumor necrosis factor-α levels. These data indicate that high dietary salt intake promotes neuroinflammation, increasing recruitment of neurons in key stress-associated brain regions and augmenting behavioral hyper-responsivity to acute psychological stress.