The synthetic thyroid hormone, levothyroxine, protects cholinergic neurons in the hippocampus of naturally aged mice

Abstract

The thyroid hormones, triiodothyronine and thyroxine, play important roles in cognitive function during the mammalian lifespan. However, thyroid hormones have not yet been used as a therapeutic agent for normal age-related cognitive deficits. In this study, CD-1 mice (aged 24 months) were intraperitoneally injected with levothyroxine (L-T4; 1.6 μg/kg per day) for 3 consecutive months. Our findings revealed a significant improvement in hippocampal cytoskeletal rearrangement of actin and an increase in serum hormone levels of L-T4-treated aged mice. Furthermore, the survival rate of these mice was dramatically increased from 60% to 93.3%. The Morris water maze task indicated that L-T4 restored impaired spatial memory in aged mice. Furthermore, level of choline acetyltransferase, acetylcholine, and superoxide dismutase were increased in these mice, thus suggesting that a possible mechanism by which L-T4 reversed cognitive impairment was caused by increased activity of these markers. Overall, supplement of low-dosage L-T4 may be a potential therapeutic strategy for normal age-related cognitive deficits.

The Synergistic Enhancing-Memory Effect of Donepezil and S 38093 (a Histamine H3 Antagonist) Is Mediated by Increased Neural Activity in the Septo-hippocampal Circuitry in Middle-Aged Mice

“…Such correlation has also been observed in aged rodents (Fu et al, 2014; Lim et al, 2015). The first clinical approach has thus consisted in inhibiting the decrease of acetylcholine (ACh) by blocking its degradation by acetylcholinesterase (AChE) in the synaptic cleft (Marighetto et al, 2008).…”

Comparative approaches to understanding thyroid hormone regulation of neurogenesis

“…Returning to the rodent models, Fu et al showed that the administration of L-T 4 to aged mice can significantly improve their learning and memory capacities, through increases of both serum and 16 brain concentrations of free T 3 and T 4 (Fu et al, 2014). Similar treatments also can counteract depression in rats and humans (Bauer et al, 2005;Ge et al, 2016;Uhl et al, 2014).…”

Morris Water Maze Training in Mice Elevates Hippocampal Levels of Transcription Factors Nuclear Factor (Erythroid-derived 2)-like 2 and Nuclear Factor Kappa B p65

“…Pharmalogical inhibition of actin polymerization within the hippocampus impairs object placement memory formation in female rats in a dose-dependent fashion (Nelson et al, 2012 ). Further, interventions that induce actin rearrangement improve MWM performance in mice (Fu et al, 2014 ) without increasing total actin, confirming actin-induced activity-dependent synaptic remodeling in a manner independent of protein synthesis. Enlargement of the actin cytoskeleton and subsequent stabilization, however, may be considered a critical determinant of memory consolidation (Rudy, 2015 ).…”