Abstract
Thyroid hormone (TH) perturbation is a common medical problem. Because of substantial public health impact, prior researchers have studied hyper- and hypothyroidism in animal models. Although most prior research focused on in utero and/or developmental effects, changes in circulating TH levels are commonly seen in elderly individuals: approximately 20% of persons older than 80 years have clinically impactful hypothyroidism and up to 5% have clinical hyperthyroidism, with women being more often affected than men. TH disease model methodology in mice have varied but usually focus on a single sex, and the impact(s) of TH perturbation on the adult brain are not well understood. We administered thyroxine to middle-aged (13 to 14 months) male and female mice to model hyperthyroidism and TH-lowering drugs propylthiouracil (PTU) and methimazole, to induce hypothyroidism. These pharmacological agents are used commonly in adult humans. Circulating TH-level changes were observed when thyroxine was dosed at 20 µg/mL in drinking water for two weeks. By contrast, PTU and methimazole did not elicit a consistent reproducible effect until two months of treatment. No substantial changes in TH levels were detected in brain tissues of treated animals; however, pronounced changes in gene expression, specifically for TH-processing transcripts, were observed following the treatment with thyroxine. Our study indicated a robust compensatory mechanism by which the brain tissue/cells minimize the TH fluctuation in CNS by altering gene expression. Neurobehavioral changes were related to the TH perturbation and suggested potential associations between cognitive status and hyper- and hypothyroidism.
Highlights
Academic Editor: Noriyuki Koibuchi yroid hormone (TH) perturbation is a common medical problem
Most prior research focused on in utero and/or developmental effects, changes in circulating TH levels are commonly seen in elderly individuals: approximately 20% of persons older than 80 years have clinically impactful hypothyroidism and up to 5% have clinical hyperthyroidism, with women being more often affected than men
No substantial changes in TH levels were detected in brain tissues of treated animals; pronounced changes in gene expression, for TH-processing transcripts, were observed following the treatment with thyroxine
Summary
Academic Editor: Noriyuki Koibuchi yroid hormone (TH) perturbation is a common medical problem. Most prior research focused on in utero and/or developmental effects, changes in circulating TH levels are commonly seen in elderly individuals: approximately 20% of persons older than 80 years have clinically impactful hypothyroidism and up to 5% have clinical hyperthyroidism, with women being more often affected than men. No substantial changes in TH levels were detected in brain tissues of treated animals; pronounced changes in gene expression, for TH-processing transcripts, were observed following the treatment with thyroxine. Hypothyroidism in humans is associated with weight gain, fatigue, muscle weakness, and impaired memory Both conditions have proven treatments, the symptom can be subtle, and diagnosis may occur years after disease onset [7,8,9]. CSF and brain TH concentrations have been correlated with age-related neurodegenerative diseases, such as LATE (Limbic-predominant age-related TDP-43 encephalopathy) and cerebrovascular disease [16,17,18,19], suggesting long-term consequences to perturbations in these pathways
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