The Role of Steroid Hormones in the Modulation of Neuroinflammation by Dietary Interventions

Abstract

Steroid hormones, such as sex hormones and glucocorticoids, have been demonstrated to play a role in different cellular processes in the central nervous system, ranging from neurodevelopment to neurodegeneration. Environmental factors, such as calorie intake or fasting frequency, may also impact on such processes, indicating the importance of external factors in the development and preservation of a healthy brain. The hypothalamic–pituitary–adrenal axis and glucocorticoid activity play a role in neurodegenerative processes, including in disorders such as in Alzheimer’s and Parkinson’s diseases. Sex hormones have also been shown to modulate cognitive functioning. Inflammation is a common feature in neurodegenerative disorders, and sex hormones/glucocorticoids can act to regulate inflammatory processes. Intermittent fasting can protect the brain against cognitive decline that is induced by an inflammatory stimulus. On the other hand, obesity increases susceptibility to inflammation, while metabolic syndromes, such as diabetes, are associated with neurodegeneration. Consequently, given that gonadal and/or adrenal steroids may significantly impact the pathophysiology of neurodegeneration, via their effect on inflammatory processes, this review focuses on how environmental factors, such as calorie intake and intermittent fasting, acting through their modulation of steroid hormones, impact on inflammation that contributes to cognitive and neurodegenerative processes.

Cytokines and Cytokine Receptors Involved in the Pathogenesis of Alzheimers Disease

“…Neuroinflammation is triggered by chronic stress in a GC receptor (GR)-dependent manner, and the reduced expression of hippocampal GRs is associated with an exaggerated response to chronic stress. These data confirm the negative feedback inhibition of hippocampal projections on the hypothalamic-pituitary-adrenocortical axis and the consequent elevation and damaging effects of circulating GCs [97,102]. …”

“…Although under physiological stress GCs generally exert anti-inflammatory effects in the CNS, the chronically elevated GC levels under stressful stimuli can potentiate neuroinflammation and increase the expression of proinflammatory cytokines, such as IL-1β and TNFα, which in turn activate many signaling pathways, including nuclear factor kappa-B (NF-κB), and microglia function [97,98]. As a result, GCs increase the vulnerability of neurons to numerous chronic stressful events, including metabolic, ischemic, excitotoxic, oxidative, and infectious insults.…”

“…Hippocampal changes arising from chronic stress via the long-term elevation of GC signaling are also evident in AD-associated processes, including aging [8,97]. Indeed, aging human subjects exhibit higher mean diurnal values of GCs, and some subjects with higher GCs later develop AD.…”

Steroids, stress and the gut microbiome‐brain axis

“…Indeed, in this context, it is important to highlight that neuroactive steroids represent important physiological regulators of the nervous system and that their levels are differentially affected in the two sexes by nervous pathologies, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, traumatic brain injury, spinal cord injury, stroke, diabetic encephalopathy, autism, anxiety and depression . Moreover, neuroactive steroids play an important role in neuroinflammatory processes in the brain, which in turn modulate behavioural states . Because these neuroinflammatory processes are responsive to peripheral immune activation, eg, by gut dysbiosis, these molecules may play an important integrative role in the gut microbiome‐brain axis.…”

“…115,116 Moreover, neuroactive steroids play an important role in neuroinflammatory processes in the brain, which in turn modulate behavioural states. [117][118][119] Because these neuroinflammatory processes are responsive to peripheral immune activation, eg, by gut dysbiosis, these molecules may play an important integrative role in the gut microbiome-brain axis.…”