Effect of the thyroid hormone receptor beta (TRbeta)-selective thyromimetic GC-1 on brain of 3xTg-AD mice

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder clinically characterized by gradual loss of memory and deterioration of other cognitive functions. Alzheimer's is the most common form of dementia among older adults. Both thyroid dysfunctions and dementia are conditions that become more prevalent with age and several studies have demonstrated a possible association between these conditions. It is possible that the thyroid hormone (TH) be involved in changes in the processing of amyloid precursor protein (APP), one of the main pathways involved with the onset of AD. However, although the study of therapeutic approaches involving TH be of great relevance, its use brings unwanted side effects such as hypermetabolism and loss of bone and muscle mass, which makes the use of selective analogues of extreme importance. In this regard, recently, the thyroid hormone receptor beta (TRbeta)-selective thyromimetic, GC-1, had its structure modified which resulted in its activation only in the Central Nervous System (CNS). Thus, the aim of the present study is to investigate the effects of GC-1 on the development of neuropathological changes and cognitive function characteristics of AD in 3xTg-AD transgenic mice. For that, we will analyze the cognitive performance of GC-1 treated 3xTg-AD mice through behavioral tests, as well as the presence of senile plaques (SPs), neurofibrillary tangles (NFTs), and neuronal density through histological studies, and the expression of genes related to the neuropathology of AD and related to cognition and memory on brain by RT-qPCR. (AU)