Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lorena, Fernanda B., Sato, Juliana M., Coviello, Beatriz Martin, Arnold, Alexandre J. T., Batistuzzo, Alice, Yamanouchi, Laís M., Dias Junior, Eduardo, do Nascimento, Bruna P. P., Fonseca, Tatiana de L., Bianco, Antonio C., Ribeiro, Miriam O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319877/
https://www.ncbi.nlm.nih.gov/pubmed/35888752
http://dx.doi.org/10.3390/metabo12070629
_version_ 1784755657475358720
author Lorena, Fernanda B.
Sato, Juliana M.
Coviello, Beatriz Martin
Arnold, Alexandre J. T.
Batistuzzo, Alice
Yamanouchi, Laís M.
Dias Junior, Eduardo
do Nascimento, Bruna P. P.
Fonseca, Tatiana de L.
Bianco, Antonio C.
Ribeiro, Miriam O.
author_facet Lorena, Fernanda B.
Sato, Juliana M.
Coviello, Beatriz Martin
Arnold, Alexandre J. T.
Batistuzzo, Alice
Yamanouchi, Laís M.
Dias Junior, Eduardo
do Nascimento, Bruna P. P.
Fonseca, Tatiana de L.
Bianco, Antonio C.
Ribeiro, Miriam O.
author_sort Lorena, Fernanda B.
collection PubMed
description 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 polymorphism. 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.
format Online
Article
Text
id pubmed-9319877
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-93198772022-07-27 Age Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism Lorena, Fernanda B. Sato, Juliana M. Coviello, Beatriz Martin Arnold, Alexandre J. T. Batistuzzo, Alice Yamanouchi, Laís M. Dias Junior, Eduardo do Nascimento, Bruna P. P. Fonseca, Tatiana de L. Bianco, Antonio C. Ribeiro, Miriam O. Metabolites Article 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 polymorphism. 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. MDPI 2022-07-08 /pmc/articles/PMC9319877/ /pubmed/35888752 http://dx.doi.org/10.3390/metabo12070629 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lorena, Fernanda B.
Sato, Juliana M.
Coviello, Beatriz Martin
Arnold, Alexandre J. T.
Batistuzzo, Alice
Yamanouchi, Laís M.
Dias Junior, Eduardo
do Nascimento, Bruna P. P.
Fonseca, Tatiana de L.
Bianco, Antonio C.
Ribeiro, Miriam O.
Age Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism
title Age Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism
title_full Age Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism
title_fullStr Age Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism
title_full_unstemmed Age Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism
title_short Age Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism
title_sort age worsens the cognitive phenotype in mice carrying the thr92ala-dio2 polymorphism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319877/
https://www.ncbi.nlm.nih.gov/pubmed/35888752
http://dx.doi.org/10.3390/metabo12070629
work_keys_str_mv AT lorenafernandab ageworsensthecognitivephenotypeinmicecarryingthethr92aladio2polymorphism
AT satojulianam ageworsensthecognitivephenotypeinmicecarryingthethr92aladio2polymorphism
AT coviellobeatrizmartin ageworsensthecognitivephenotypeinmicecarryingthethr92aladio2polymorphism
AT arnoldalexandrejt ageworsensthecognitivephenotypeinmicecarryingthethr92aladio2polymorphism
AT batistuzzoalice ageworsensthecognitivephenotypeinmicecarryingthethr92aladio2polymorphism
AT yamanouchilaism ageworsensthecognitivephenotypeinmicecarryingthethr92aladio2polymorphism
AT diasjunioreduardo ageworsensthecognitivephenotypeinmicecarryingthethr92aladio2polymorphism
AT donascimentobrunapp ageworsensthecognitivephenotypeinmicecarryingthethr92aladio2polymorphism
AT fonsecatatianadel ageworsensthecognitivephenotypeinmicecarryingthethr92aladio2polymorphism
AT biancoantonioc ageworsensthecognitivephenotypeinmicecarryingthethr92aladio2polymorphism
AT ribeiromiriamo ageworsensthecognitivephenotypeinmicecarryingthethr92aladio2polymorphism