Hydrocortisone Mitigates Alzheimer’s-Related Cognitive Decline through Modulating Oxidative Stress and Neuroinflammation

Abstract

Alzheimer’s disease (AD), an age-related degenerative disorder, is characterized by β-amyloid deposition, abnormal phosphorylation of tau proteins, synaptic dysfunction, neuroinflammation, and oxidative stress. Despite extensive research, there are no medications or therapeutic interventions to completely treat and reverse AD. Herein, we explore the potential of hydrocortisone (HC), a natural and endogenous glucocorticoid known to have potent anti-inflammatory properties, in an Aβ1–42-induced AD mouse model. Our investigation highlights the beneficial effects of HC administration on cognitive impairment, synaptic function enhancement, and neuronal protection in Aβ1–42-induced AD mice. Notably, HC treatment effectively suppresses the hyperactivation of microglia and astrocytes, leading to a reduction in proinflammatory factors and alleviation of neuroinflammation. Furthermore, HC intervention demonstrates the capacity to mitigate the generation of ROS and oxidative stress. These compelling findings underscore the potential therapeutic application of HC in AD and present promising opportunities for its utilization in AD prevention and treatment. The implications drawn from our findings indicate that hydrocortisone holds promise as a viable candidate for adjunctive use with other anti-AD drugs for the clinical management of patients presenting with moderate to severe AD.

Peripheral inflammation as a potential mechanism and preventive strategy for perioperative neurocognitive disorder under general anesthesia and surgery

“…Additionally, Hydrocortisone can also modulate the release of neuropeptides and the speed of neuronal transmission, exerting positive effects on the processes of learning and memory ( Flanigan et al, 2020 ). Research has also shown that hydrocortisone can reduce the levels of inflammatory mediators in the brain, alleviate neuroinflammation, and subsequently relieve memory impairment and depressive symptoms, an especially important consideration for elderly and other individuals affected by cognitive impairments ( Li et al, 2023 ). Meanwhile, androgenic steroids are a class of hormones that exist in both male and female bodies, of which testosterone is the most typical.…”