Avaliação do efeito do hipotireoidismo na memória de roedores de acordo com o sexo e fase do dia

Abstract

Hypothyroidism is a common endocrine metabolic disorder diagnosed by high levels of Thyroid Stimulating Hormone (TSH) and low levels of thyroxine (T4) and triiodothyronine (T3), with higher prevalence in woman and elderly. Among the wide variety of symptoms, hypothyroid patients often complain about the memory’s impairment. Moreover, there is an association between thyroid disorders and circadian clock disruption, which in turn, is linked with memory deficiency. Thus, the present study aimed to investigate the effects of hypothyroidism on object recognition memory (MRO) in male and female C57BL/6J mice during active and rest phases. The animals were divided into Control (C) and Hypothyroid (H) groups. Hypothyroidism was induced by methimazole (0.01%) and perchlorate (0.1%) treatment in the drinking waterfor 21 days. MRO was evaluated at ZTs 2-4 (rest phase) and ZT14-16 (active phase), before and after hypothyroidism induction. After that, the animals were euthanized every 4h for 24h. Heart weight and tibia length were measured. The anterior pituitary and the brain were collected and immediately frozen. Subsequently, RNA extraction and RT-qPCR were performed to evaluate the expression of the transcripts that encode Tshb in anterior pituitary and the core clock components (Bmal1, Per2, Nr1d1 and Cry1) in the dorsal hippocampus by RT- qPCR.The treatment’s effectiveness was confirmed by the increased Tshb mRNA expression in anterior pituitary gland and the reduced heart weight / tibia length ratio. The results showed that under Control conditions, male and female mice recognize the familiar object in a time-independent way, showing no differences in task performance. After the hypothyroidism induction, animals of both sexes were not able to perform the task in the rest phase (ZTs 2-4). In the active phase (ZTs 14-16), the femalesshowed a loss in ORM, while the males performed the task and recognized the familiar object, however, they presented a slower execution of the task, suggesting a lower performance. Moreover, the daily oscillation pattern of dorsal hipocampus circadian clock gene expression showed significant changes for time (ZT), treatment and/or sex main factors. Thus, we conclude that hypothyroidism differentially impairs the memory of miceaccording to sex and time- of- day. Furthermore, our results suggest a functional role of thyroid hormones, including signaling to the biological clock of brain areas related to mnemonic processes.