Thyroid hormones regulate anxiety in the male mouse

Area of Science:

• Neuroendocrinology
• Behavioral Neuroscience
• Molecular Endocrinology

Background:

• Thyroid hormones influence mood disorders, but mechanisms in adults are unclear.
• Rodent models often focus on perinatal thyroid dysfunction, not adult onset.
• Thyroid hormone receptors (TRs) modulate gene expression through liganded and unliganded actions in the limbic system.

Purpose of the Study:

• Investigate the behavioral consequences of adult-onset hypothyroidism in mice.
• Differentiate the roles of unliganded versus liganded thyroid hormone receptor actions.
• Examine the effects of tri-iodothyronine (T3) and thyroxine (T4) supplementation on anxiety behaviors.

Main Methods:

• Induced adult-onset hypothyroidism in male mice.
• Administered tri-iodothyronine (T3) or thyroxine (T4) for supplementation.
• Assessed anxiety-like behaviors using open field and light-dark transition tests.
• Quantified spine density in the hippocampus (CA1) and amygdala.

Main Results:

• Adult-onset hypothyroidism induced mild anxiety-like behaviors in male mice.
• This anxiogenic effect may stem from unliganded thyroid hormone receptor activity.
• T3 or T4 supplementation normalized anxiety behaviors.
• T3 supplementation, but not T4, reduced spine density in the CA1 hippocampus and central amygdala.

Conclusions:

• Adult-onset hypothyroidism in male mice can lead to anxiety, possibly through unliganded TR actions.
• Thyroid hormone replacement therapy (T3/T4) can reverse these anxiety phenotypes.
• T3-mediated anxiety reduction may involve decreased neuronal excitability in limbic circuits, indicated by altered spine density.