Age Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism

dc.contributor.authorLorena F.B.
dc.contributor.authorSato J.M.
dc.contributor.authorCoviello B.M.
dc.contributor.authorArnold A.J.T.
dc.contributor.authorBatistuzzo A.
dc.contributor.authorYamanouchi L.M.
dc.contributor.authorDias Junior E.
dc.contributor.authorDo Nascimento B.P.P.
dc.contributor.authorFonseca T.L.
dc.contributor.authorBianco A.C.
dc.contributor.authorRibeiro M.O.
dc.date.accessioned2024-03-12T19:14:36Z
dc.date.available2024-03-12T19:14:36Z
dc.date.issued2022
dc.description.abstract© 2022 by the authors. Licensee MDPI, Basel, Switzerland.The Thr92Ala-Dio2 polymorphism has been associated with reduced cognition in 2-month-old male mice and increased risk for cognitive impairment and Alzheimer’s disease in African Americans. This has been attributed to reduced thyroid hormone (TH) signaling and endoplasmic reticulum (ER) stress in the brain. Here we studied the Thr92Ala-Dio2 mouse model and saw that older male mice (7–8-month-old) exhibited a more severe cognition impairment, which extended to different aspects of declarative and working memories. A similar phenotype was observed in 4–5-month-old female mice. There were no structural alterations in the prefrontal cortex (PFC) and hippocampus of the Thr92Ala-Dio2 mouse. Nonetheless, in both male and female PFC, there was an enrichment in genes associated with TH-dependent processes, ER stress, and Golgi apparatus, while in the hippocampus there was additional enrichment in genes associated with inflammation and apoptosis. Reduced TH signaling remains a key mechanism of disease given that short-term treatment with L-T3 rescued the cognitive phenotype observed in males and females. We conclude that in mice, age is an additional risk factor for cognitive impairment associated with the Thr92Ala-Dio2 poly-morphism. In addition to reduced TH signaling, ER-stress, and involvement of the Golgi apparatus, hippocampal inflammation and apoptosis were identified as potentially important mechanisms of a disease.
dc.description.issuenumber7
dc.description.volume12
dc.identifier.doi10.3390/metabo12070629
dc.identifier.issn2218-1989
dc.identifier.urihttps://dspace.mackenzie.br/handle/10899/34343
dc.relation.ispartofMetabolites
dc.rightsAcesso Aberto
dc.subject.otherlanguagecognition
dc.subject.otherlanguagethyroid hormone
dc.subject.otherlanguagetype 2 deiodinase
dc.titleAge Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism
dc.typeArtigo
local.scopus.citations3
local.scopus.eid2-s2.0-85134496771
local.scopus.updated2024-12-01
local.scopus.urlhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85134496771&origin=inward
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