Aryl Hydrocarbon Receptor in Post-Mortem Hippocampus and in Serum from Young, Elder, and Alzheimer’s Patients

Abstract

One of the characteristics of the cerebral aging process is the presence of chronic inflammation through glial cells, which is particularly significant in neurodegeneration. On the other hand, it has been demonstrated that the aryl hydrocarbon receptor (AHR) participates in the inflammatory response. Currently, evidence in animal models shows that the hallmarks of aging are associated with changes in the AHR levels. However, there is no information concerning the behavior and participation of AHR in the human aging brain or in Alzheimer’s disease (AD). We evaluated the expression of AHR in human hippocampal post-mortem tissue and its association with reactive astrocytes by immunohistochemistry. Besides this, we analyzed through ELISA the AHR levels in blood serum from young and elder participants, and from AD patients. The levels of AHR and glial fibrillar acid protein were higher in elder than in young post-mortem brain samples. AHR was localized mainly in the cytosol of astrocytes and displayed a pattern that resembles extracellular vesicles; this latter feature was more conspicuous in AD subjects. We found higher serum levels of AHR in AD patients than in the other participants. These results suggest that AHR participates in the aging process, and probably in the development of neurodegenerative diseases like AD.

Obeticholic Acid Inhibits Anxiety via Alleviating Gut Microbiota-Mediated Microglia Accumulation in the Brain of High-Fat High-Sugar Diet Mice

“…The indole derivatives were potential ligands of aryl hydrocarbon receptor (AhR) [ 14 ], which is a critical node in linking microbial tryptophan metabolites to brain function [ 63 ], and was involved in neuroinflammation [ 64 ]. In agreement with the findings of enhanced AhR activation in neuropsychiatric disorders of cognitive impairment of AD patients [ 65 ] and depression mice [ 66 ], the enriched indole derivatives were found in our HFHS diet-MDs mice and significantly related with the levels of circulating bile acid TCA and anxiety-like behavior.…”

The Aryl Hydrocarbon Receptor: A Mediator and Potential Therapeutic Target for Ocular and Non-Ocular Neurodegenerative Diseases

“…A different relationship has been reported between the AHR and another neurodegenerative disease, Alzheimer's disease (AD). An increase in AHR expression in the astrocytes of aged individuals and AD patients has been observed [92], along with enhanced AHR protein levels in AD patients, while there were no differences between young and old donors. These studies suggest that the AHR is implicated in the aging process of the brain and possibly in the development of AD through its effects on astrocytes.…”

Dietary and environmental factors have opposite AhR-dependent effects on C. elegans healthspan

“…The effect of AHR-1 on aggregation-prone diseases may suggest novel targeted therapeutic options of relevance for different age-associated diseases. Interestingly, prototype AhR activators, such as TCDD and BaP, were shown to contribute to the development and progression of age-associated diseases (reviewed in [ 62 , 63 ]) in different model systems [ 64 ] and a recent study showed increased AhR levels in serum brains of Alzheimer’s disease patients [ 65 ]. On the other hand, reduced α-synuclein levels were observed in the mouse ventral midbrain upon TCDD-induced AhR-dependent Parkin expression [ 66 ].…”