Experimentally Induced Hyperthyroidism Disrupts Hippocampal Long-Term Potentiation in Adult Rats

Abstract

Background: Manipulating thyroid hormones has been shown to influence learning and memory. Although a large body of literature is available on the effects of thyroid hormone deficiency on learning and memory functions during developmental or adult-onset hypothyroidism, electrophysiological findings are limited. This limitation is especially notable with respect to thyroxine administration in adult, normothyroid animals. Methods: Experiments were carried out on 12 adult male Wistar rats, each 9–10 months of age. Rats were randomly divided into hyperthyroid (0.2 mg/kg/day intraperitoneal thyroxine injection, for 21 days) and control groups (n = 6 animals in each group). Following spatial learning performance tests on hyperthyroid and control groups, rats were anesthetized with urethane and placed in a stereotaxic frame. A bipolar, tungsten electrode was used to stimulate the medial perforant path. A glass micropipette was inserted within the granule cell layer of the ipsilateral dentate gyrus to record field excitatory postsynaptic potentials (fEPSP). Following a 15-min baseline recording of fEPSPs, long-term potentiation (LTP) was induced by four sets of tetanic pulse trains. Results: Thyroxine-treated rats showed significantly worse performance in the spatial memory task and attenuated input-output relationships in the electrophysiological analyses. Treated rats also showed a lower efficacy of LTP induction when compared with controls. Conclusion: The present study provides clear in vivo evidence for the action of L-thyroxine in the impairment of synaptic plasticity and in inducing spatial memory task deficits in adult rats. These findings may explain the complaints of cognitive function reductions in hyperthyroid patients.

Low-frequency stimulation induces a durable long-term depression in young adult hyperthyroid rats

“…LTD is necessary to prevent strengthening synapses from ultimately reaching a ceiling level of efficiency, which would inhibit the encoding of new information [24]. We have shown previously that L-thyroxine-treated adult rats show a lower efficacy of LTP induction compared with controls [18]. The present results, in combination with our previous findings, suggest that hyperthyroidism alters the direction of plasticity and promotes LTD over LTP.…”

“…An impairment in LTP [18,20] has been reported previously in hyperthyroidism during the early and late stages of development. This study provides the first characterization of LTD in adult hyperthyroid rats and shows that LFS-induced LTD plasticity is more durable under conditions of increasing levels of free L-thyroxine.…”

“…All rats were administered a 1 ml intraperitoneal injection of either L-thyroxine (0.2 mg/kg body mass) or vehicle for 21 days [17]. We previously reported that this treatment regime produced a marked increase in total T4 [18]. In the present study, we measured the free levels of THs.…”

“…The details of the electrophysiology experiments have been described elsewhere [8,18]. Briefly, extracellular field potentials were recorded from the dentate gyrus (DG) [from the bregma (mm): AP: -3.5, ML: 2.15] in response to the stimulation of the perforant pathway (PP) [from the bregma (mm): AP: -6.5, ML: 4.2] in 2-monthold rats (n = 8 for each group) under urethane anesthesia.…”

Hipertiroidili sıçanlarda uzamsal öğrenme performansına cinsiyetin etkisi

“…Hipotiroidili sıçanlarda da öğrenme ve UDG'de bozulma olduğu bildirilmiştir (32)ve bu hipotiroidili sıçanlar tiroid hormonu ile tedavi edildiğinde UDG'deki bu bozukluğun düzeldiği gözlenmiştir. Yapmış olduğumuz daha önceki bir çalışmada, erişkin hipertiroidili sıçanlarda dentat girus nöronlarının plastisitesinde değişiklik olduğunu, hipertiroidili sıçanların elektrofizyolojik analizlerinde zayıflamış girdi-çıktı ilişkileri olduğunu ve hipertiroidili sıçanların uzamsal olarak daha kötü performans gösterdiğini bildirdik (33). Graves hastalığı oluşturulan bir çalışmada sağlık-lı gruplarla karşılaştırıldığında, bellek ve yürütücü işlev-lerde önemli bozukluklar kaydedilmiş, graves hastalığı olan hasta grubunda, depresyon belirtilerinin yanında ayrıca hastaların bilişsel işlev bozuklukları saptanmıştır (34).…”