title: Adult-onset hypothyroidism enhances fear memory and upregulates mineralocorticoid and glucocorticoid receptors in the amygdala.
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.
authors: Department of Nervous System and Endocrine Pathophysiology, Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
authors: Ana
authors: A
authors: Montero-Pedrazuela
authors: Iván
authors: I
authors: Fernández-Lamo
authors: María
authors: M
authors: Alieva
authors: Inmaculada
authors: I
authors: Pereda-Pérez
authors: César
authors: C
authors: Venero
authors: Ana
authors: A
authors: Guadaño-Ferraz
mesh_terms: D000328:Adult; D017668:Age of Onset; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D005239:Fear; D006801:Humans; D007037:Hypothyroidism / Q000378:metabolism / Q000523:psychology*; D008568:Memory; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*
chemical_list: D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid