Abstract
Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment.
Highlights
Morphological and functional brain adaptability is the basis for learning and memory
Our results show that euthyroidism is necessary for proper processing of emotional memories, as hypothyroidism enhances fear memory, delays extinction and exacerbates spontaneous recovery of fear memory
To evaluate the effects of adult-onset hypothyroidism on functional alterations on fear memory, we used Pavlovian contextual and auditory delay fear conditioning tests following the experimental design explained in Methods (Experiment 1) and Figure 1A
Summary
Morphological and functional brain adaptability is the basis for learning and memory. The integration of both external and internal signals as hormones modulates this plasticity. A large number of epidemiological and experimental studies have shown that deficiencies in thyroid hormones (TH, triiodothyronine or T3 and thyroxine or T4) during critical periods of development induce irreversible brain damage affecting learning and memory capacities [2,3]. Over the last few decades, a great effort has been made to implement programs for the prevention of neonatal hypothyroidism [4]. Less attention has been paid to adult-onset hypothyroidism and its consequences, as it is a frequent condition in humans with the prevalence increasing with age [5,6]
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