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• W3034602289 abstract "Visual Abstract Export Background Uremic toxicity may play a role in the elevated risk of developing cognitive impairment found among patients with CKD. Some uremic toxins, like indoxyl sulfate, are agonists of the transcription factor aryl hydrocarbon receptor (AhR), which is widely expressed in the central nervous system and which we previously identified as the receptor of indoxyl sulfate in endothelial cells. Methods To characterize involvement of uremic toxins in cerebral and neurobehavioral abnormalities in three rat models of CKD, we induced CKD in rats by an adenine-rich diet or by 5/6 nephrectomy; we also used AhR−/− knockout mice overloaded with indoxyl sulfate in drinking water. We assessed neurologic deficits by neurobehavioral tests and blood-brain barrier disruption by SPECT/CT imaging after injection of 99mTc-DTPA, an imaging marker of blood-brain barrier permeability. Results In CKD rats, we found cognitive impairment in the novel object recognition test, the object location task, and social memory tests and an increase of blood-brain barrier permeability associated with renal dysfunction. We found a significant correlation between 99mTc-DTPA content in brain and both the discrimination index in the novel object recognition test and indoxyl sulfate concentrations in serum. When we added indoxyl sulfate to the drinking water of rats fed an adenine-rich diet, we found an increase in indoxyl sulfate concentrations in serum associated with a stronger impairment in cognition and a higher permeability of the blood-brain barrier. In addition, non-CKD AhR−/− knockout mice were protected against indoxyl sulfate–induced blood-brain barrier disruption and cognitive impairment. Conclusions AhR activation by indoxyl sulfate, a uremic toxin, leads to blood-brain barrier disruption associated with cognitive impairment in animal models of CKD." @default.
• W3034602289 created "2020-06-19" @default.
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• W3034602289 date "2020-06-10" @default.
• W3034602289 modified "2023-10-17" @default.
• W3034602289 title "Uremic Toxic Blood-Brain Barrier Disruption Mediated by AhR Activation Leads to Cognitive Impairment during Experimental Renal Dysfunction" @default.
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• W3034602289 doi "https://doi.org/10.1681/asn.2019070728" @default.
• W3034602289 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7350986" @default.
• W3034602289 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32527975" @default.
• W3034602289 hasPublicationYear "2020" @default.
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