Melatonin inhibits neuronal dysfunction-associated with neuroinflammation by atopic psychological stress in NC/Nga...

Atopic dermatitis (AD), also known as atopic eczema, is chronic pruritic skin disease. AD can increase psychological stress as well, increasing glucocorticoid release and exacerbating the associated symptoms. Chronic glucocorticoid elevation disturbs neuroendocrine signaling and can induce neuroinflammation, neurotoxicity, and cognitive impairment; however, it is unclear whether AD-related psychological stress elevates glucocorticoids enough to cause neuronal damage. Therefore, we assessed the effects of AD-induced stress in a mouse AD model. AD-related psychological stress increased astroglial and microglial activation, neuroinflammatory cytokine expression, and markers of neuronal loss. Notably, melatonin administration inhibited the development of skin lesions, scratching behavior, and serum IgE levels in the model mice, and additionally caused a significant reduction in corticotropin-releasing hormone responsiveness, and a significant reduction in neuronal damage. Finally, we produced similar results in a corticosterone-induced AD-like skin model. This is the first study to demonstrate that AD-related psychological stress increases neuroendocrine dysfunction, exacerbates neuroinflammation, and potentially accelerates other neurodegenerative disease states.