Mechanisms involved in cognitive impairment in female mice carrying the Dio2, Thr92Ala-D2 polymorphism.

• Grant number: 23/03031-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2023
• End date: March 11, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Miriam Oliveira Ribeiro
• Grantee: Beatriz Martin Coviello
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

A single nucleotide polymorphism in the gene encoding the type 2 (D2) deiodase enzyme, DIO2 (rs225014), results in a single amino acid substitution of threonine (Thr) for alanine (Ala) at position 92 in the D2 protein (Thr92AlaD2) and is present in about 12 to 36% of the population. Studies in young Ala92-D2 female mice showed significant cognitive impairment accompanied by alterations in genes involved in neuroinflammation. Considering that neuroinflammation is associated with depressive and anxiety-like behaviors and that females exhibit a higher prevalence of depression and anxiety disorder, we hypothesized that the presence of the polymorphism is associated with depression and anxiety in Ala92-D2 females. To test our hypothesis, we will characterize the behavior of females at 2 and 4 months of age by a battery of behavioral tests and assess neuroinflammation by labeling glia cells by infusion of the radio drug C-PK11195 and by PET/CT, evaluation of GFAP and Iba-1 expression by immunohistochemistry as a measure of activation of astrocytes and mycroglia. In addition, to confirm activation of the mycroglia or astrocytes, we will evaluate the transcriptome by single cell RNA sequencing.Translated with www.DeepL.com/Translator (free version)