Adult-Onset Hypothyroidism Enhances Fear Memory and Upregulates Mineralocorticoid and Glucocorticoid Receptors in the Amygdala 英文参考文献.docVIP

Adult-OnsetHypothyroidismEnhancesFearMemoryand UpregulatesMineralocorticoidandGlucocorticoid ReceptorsintheAmygdala AnaMontero-Pedrazuela1,Iva′nFerna′ndez-Lamo1¤a,Mar?′aAlieva1¤b,InmaculadaPereda-Pe′rez2,Ce′sar Venero2*,AnaGuadan?o-Ferraz1* 1DepartmentofNervousSystemandEndocrinePathophysiology,InstitutodeInvestigacionesBiome′dicasAlbertoSols,ConsejoSuperiordeInvestigacionesCient?′ficas- UniversidadAuto′nomadeMadrid,Madrid,Spain,2DepartmentofPsychobiology,UniversidadNacionaldeEducacio′naDistancia,Madrid,Spain Abstract Hypothyroidismisthemostcommonhormonaldiseaseinadults,whichisfrequentlyaccompaniedbylearningandmemory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memoryarepoorlyunderstoodandoftenunderestimated.Toevaluatetheconsequencesofhypothyroidismonemotional 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,memoryextinctionwasdelayedandspontaneousrecoveryoffearmemorywasexacerbatedinhypothyroidrats. 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 basolateralnucleioftheamygdala,nucleithatarecriticallyinvolvedinthecircuitryoffearmemory.Ourresultsdemonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotionalmemories.Furthermore,ourfindingssuggestthatenhancedcorticosteronesignalingintheamygdalaisinvolved 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 abnormallevelsofthyroidhormones,