PTU‐induced hypothyroidism in rats leads to several early neuropathological signs of Alzheimer's disease in the hippocampus and spatial memory impairments

Abstract

The multifactorial causes impacting the risk of developing sporadic forms of Alzheimer's disease (AD) remain to date poorly understood. Epidemiologic studies in humans and research in rodents have suggested that hypothyroidism could participate in the etiology of AD. Recently, we reported that adult-onset hypothyroidism in rats favors β-amyloid peptide production in the hippocampus. Here, using the same hypothyroidism model with the antithyroid molecule propythiouracyl (PTU), we further explored AD-related features, dysfunctional cell-signaling mechanisms and hippocampal-dependent learning and memory. In vivo MRI revealed a progressive decrease in cerebral volume of PTU-treated rats. In the hippocampus, hypothyroidism resulted in tau hyperphosphorylation and increases in several proinflammatory cytokines. These modifications were associated with impaired spatial memory and reduced hippocampal expression of signaling molecules important for synaptic plasticity and memory, including neurogranin, CaMKII, ERK, GSK3β, CREB, and expression of the transcription factor EGR1/Zif268. These data strengthen the idea that hypothyroidism represents an important factor influencing the risk of developing sporadic forms of AD.

Protective effects of GM-CSF in experimental neonatal hypothyroidism

“…Similar to previous findings, the fall in THs associated with elevated TSH, GH and IGF-II [47,48]. The elevated TNF-ɑ level indicated an increase in proinflammatory cytokine release in hypothyroidism [49].…”

Acute Treatment with T-Type Calcium Channel Enhancer SAK3 Reduces Cognitive Impairments Caused by Methimazole-Induced Hypothyroidism Via Activation of Cholinergic Signaling

“…A recent study in rats indicated that adult hypothyroidism might be a risk factor for the development of dementia and Alzheimer's disease [48]. TH insufficiency, even for a short period, might cause irreversible brain damage [49] and extensively elicits OE degeneration in rodents [39,50].…”

The WOMED model of benign thyroid disease: Acquired magnesium deficiency due to physical and psychological stressors relates to dysfunction of oxidative phosphorylation

“…This last action is related (again) to changes in the hippocampus [164] . These experimental findings are of interest to our research because they correlate with the effects of thyroid function on the hippocampus [165] , [166] , [167] , [168] as well as to psychological stress due to trauma [46] , [134] , [169] , [170] . As a corollary of these data we propose that magnesium deficiency could be involved in altered cognition development, an issue that has been seen almost exclusively to be related to thyroid function.…”