Thyroid dysfunction and Alzheimer’s disease
Dates:18 September 2017 - 29 June 2018
Date limite de candidature:29 June 2018
~ Sept-Dec 2017 (to be discussed)
~ Jan-March 2018
~ April-June 2018
Factors impacting the risk of developing sporadic forms of Alzheimer’s disease (AD), which accounts for over 99% of the cases, remain poorly understood. Thyroid dysfunction is a risk factor for Alzheimer’s disease (AD) [Davis et al, 2008 Curr Aging Sci 1:175–81]. We showed that hypothyroidism in rats leads to early brain changes reminiscent of AD, notably hippocampal A and proinflammatory cytokine production, Tau phosphorylation associated with memory deficits [Ghenimi et al, 2010 J Neuroendocrinol 22:951; Chaalal et al, 2014 Hippocampus 24:1381]. Our recent findings indicate that thyroid hormone (TH) supplementation rescues most of these alterations. Our general objective is now to achieve new insights into the relationships between localized hypothyroidism and AD-related pathological hallmarks.Recent evidence suggests a detrimental impact of hypothyroidism on (1) synaptic transmission and memory, (2) neuronal and astrocytes survival [Cortes et al, 2012 Thyroid 22:9]. TH is also considered as an important signaling factor that affects glial changes [Noda, 2015 Front Cell Neurosci 9:194]. Changes of microglia and astrocytes functions may contribute to the early inflammatory response and modulate the level of Aβ peptide and Tau phosphorylation [Morales et al, 2015 Front Cell Neurosci 8:112]. The project will be directed at characterizing the inflammatory response and determining its potential role in the sequence of events that leads to a favorable environment for the development of AD pathology under conditions of hypothyroidism.
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