Neonatal hyperthyroidism disrupts hippocampal LTP and spatial learning

Pavlides, Constantine; Westlind‐Danielsson, Anita; Nyborg, Helmuth; McEwen, Bruce S.

doi:10.1007/bf00231740

Cited by 52 publications

(28 citation statements)

References 27 publications

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“…In parallel with our findings, it was reported that the efficacy of LTP induction was significantly attenuated in T3-treated rats, indicating that neonatal hyperthyroidism disturbs LTP in the DG of the hippocampal formation [36]. Furthermore, local T4 microinjection in the DG in normothyroid and propylthiouracil-treated rats produced an immediate and long-lasting decrease in the PS amplitude recorded from the DG following stimulation of the medial perforant pathway [51].…”

Section: Discussionsupporting

confidence: 71%

“…It would be expected from the observed impairment of PTP and LTP in hyperthyroidism that hyperthyroid rats would perform worse on spatial tasks than control rats, as seen in the present study. In accordance with our findings, it was reported that T3-treated rats were significantly impaired in their performance on a spatial task (Y-maze) and showed attenuated LTP induction when compared with their matched controls [36]. These findings do not agree with the study of Smith et al [55], however, who reported that the group receiving the highest dose of T4 (5 mg) showed improved performances on day 4 [55].…”

Section: Discussioncontrasting

confidence: 41%

“…Spatial learning and memory deficits have been described in the genetically hypothyroid hyt/hyt mouse [32] and in congenitally hypothyroid animals [33,34,35]. It is surprising that even T3-treated rats showed impaired performance on a spatial task when compared to their matched controls [36], a finding that may be explained by the nongenomic effects of thyroid hormones. Several groups have shown that thyroid hormones inhibit L -[ 3 H]glutamate binding [37], regulate N-methyl- D -aspartate (NMDA) receptor subunit expression in the hippocampus [38], and decrease NMDA-evoked currents in rat hippocampal cultures [39].…”

Section: Introductionmentioning

confidence: 99%

“…LTP in hippocampal synapses has been shown to be impaired in both hypothyroid adult rats [41,42,43,44] and in T3-treated, hyperthyroid neonatal rats [36]. The observed impairment in plasticity when animals are in a hypothyroid state may result from changes in hippocampal neurogenesis, resulting in impaired synaptic plasticity and deficits in spatial memory tasks [27].…”

Section: Introductionmentioning

confidence: 99%

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

Taşkın

Artis²,

Bitiktas³

et al. 2011

Neuroendocrinology

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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.

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Section: Discussionsupporting

confidence: 71%

Section: Discussioncontrasting

confidence: 41%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Taşkın

Artis²,

Bitiktas³

et al. 2011

Neuroendocrinology

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“…Neonatal gelişim aşamala-rında aşırı tiroid hormonunun sıçan hipokampal oluşu-munda belirgin nörokimyasal ve morfolojik değişiklikler oluşturduğu gösterilmiştir. Bu değişikliklerin fonksiyonel önemini anlamak için, uzamsal öğrenme ve uzun dönemli güçlenme (UDG) çalışmasında, T3 verilen hayvanlarda UDG yanıtlarının azaldığı ve neonatal hipertiroidizmde hipokampal UDG'nin bozulduğu gösterilmiştir (31). 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.…”

Section: Tartışma Ve Sonuçunclassified

Hipertiroidili sıçanlarda uzamsal öğrenme performansına cinsiyetin etkisi

Tan¹,

Babur²,

Örnek³

et al. 2018

GenelTipDer

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Genel Tıp Derg 2018;28(2):69-75 69 Öz Amaç: Gelişimsel dönemdeki hipotiroidi ve hipertiroidi gibi tiroid hormon seviyesi bozukluklarında, beyinde yapısal ve fonksiyonel değişikliklerin olduğu deneysel çalışmalarda gösterilmiştir. Bu değişikliklerin, hipokampüsün önemli rol oynadığı öğrenme ve bellek gibi bilişsel süreçlerde bozulmalara ve nörolojik bozukluklara neden olduğu bilinmektedir. Bu amaçla hipertiroidili erkek ve dişi sıçanlar arasında uzamsal öğrenme performansının araştırılması amaçlanmıştır. Gereç ve Yöntem:Hipertiroidi oluşturmak için erkek ve dişi sıçanlara 21 gün süreyle 0,2 mg/kg dozda L-Tiroksin İp olarak uygulanmıştır. Öğrenme ve bellek performansını değerlendirmek için Morris su tankı testi (MST) kullanılmıştır. Bulgular:Tekrarlayan ölçümlerle ANOVA testi yapıldığında cinsiyet faktörü platforma olan ortalama uzaklığı anlamlı (p<0,001) derecede etkilemiştir. İlerleyen gün ve triallerde dişi sıçanların platforma olan ortalama uzaklıkları erkek sıçanlara göre daha fazladır. Bu veri dişi sıçanların platforma daha uzak mesafede yüzdüklerini ve platformu daha geç sürede bulduklarını ifade etmektedir. Cinsiyet faktörünün bu etkisi hipertiroidi durumundan etkilenmemiştir. Bellek performansı bakımından hipertiroidi grubu sıçanlar kontrol grubuna göre anlamlı derecede (p=0,023) bir azalma göstermiştir. Ayrıca cinsiyet farklılığının hipertirodi durumundaki bu azalmayı arttırdığı (p=0,020) gözlenmiştir. Dişi hipertiroidili sıçanların hedef kadranda bulunma oranlarının daha az olduğu gözlenmiştir.Sonuç: Sonuç olarak hipertiroidili sıçanlarda uzamsal öğrenme ve bellek performansı cinsiyete bağlı olarak farklılık göstermektedir.Anahtar Kelimeler: Hipertiroidizm; öğrenme ve bellek; hipokampüs; morris su tankı Abstract Objective: In thyroid hormone level disorders such as hypothyroidism and hyperthyroidism in developmental period, experimental studies have shown that structural and functional changes in the brain. These changes are known to cause neurological disorders and impairments in cognitive processes, such as learning and memory, in which the hippocampus plays an important role. For this purpose, it is aimed to investigate spatial learning performance between hyperthyroidized male and female rats. Materials and Methods:Male and female rats were administered with L-thyroxine intraperitoneally at a dose of 0.2 mg/kg for 21 days to induce hyperthyroidism. Morris water maze (MWM) was used to assess learning and memory performance.Results: When repeated ANOVA tests were performed, the gender factor significantly affected the mean distance to the platform (p <0.001). In the following days and trials, the average distance of female rats to the platform is greater than male rats. This data suggest that female rats were swum longer distance to the platform and found the platform later. This effect of the gender factor was not affected by hyperthyroidism. In terms of memory performance, hyperthyroid group rats showed a significant decrease compared to the control group (p=0,023). It was also observed that gend...

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Selective vulnerability of the hippocampal pyramidal neurons to hypothyroidism in male and female rats

Madeira¹,

Sousa²,

Lima-Andrade³

et al. 1992

J of Comparative Neurology

122

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Thyroid hormone deficiency has long been considered to affect profoundly such cognitive functions as learning and memory, which are known to depend on the structural integrity of the hippocampal formation. Since we previously found that the number of granule cells of the dentate gyrus is reduced in hypothyroid animals, we decided to extend our observations to the pyramidal cells of the hippocampus in order to gain further insight into the effects of hypothyroidism upon the other neuronal links of the hippocampal trisynaptic circuitry, inasmuch as CA1 neurons are known to be particularly vulnerable to aggressive agents. Groups of 6 male and 6 female rats aged 30 and 180 days were analysed separately after being treated as follows: (1) hypothyroid from day 0 until day 30 (30-day-old hypothyroid group); (2) respective 30-day-old control; (3) hypothyroid from day 0 until day 180 (180-day-old hypothyroid group); (4) hypothyroid until day 30 and thenceforth maintained euthyroid (recovery group); (5) hypothyroid since day 30 (adult hypothyroid group); and (6) respective 180-day-old control. The volume of the pyramidal cell layer of the CA1 and CA3 regions and the numerical density of the respective neurons were evaluated, thereby allowing us to estimate the total number of pyramidal cells in each hippocampal region. The areal density and the mean nuclear volume of CA1 and CA3 pyramidal cells were also estimated. In the CA3 region, we found that hypothyroidism, whatever its duration and time of onset, induces a reduction in the volume of the pyramidal cell layer and a parallel increase in the numerical density of its neurons, without interfering with the total number of pyramidal cells. Conversely, in the CA1 region, thyroid hormone deficiency started either neonatally or during maturity was found to lead to a decrease in the total number of pyramidal cells. Reductions ranging between 14.2 and 22.5% were found in 30 and 180-day-old hypothyroid groups. The reestablishment of a euthyroid state did not ameliorate the referred neuronal loss. The present results support the view that hypothyroidism induces small alterations in the structural organization of the hippocampal CA3 region, contrary to what happens in CA1 in which neuronal death occurs. Furthermore, the data presented herein demonstrate that the total number of CA1 pyramidal cells displays sexual dimorphism that is not affected by thyroid hormone manipulations.(ABSTRACT TRUNCATED AT 400 WORDS)

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Neonatal hyperthyroidism disrupts hippocampal LTP and spatial learning

Cited by 52 publications

References 27 publications

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

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

Hipertiroidili sıçanlarda uzamsal öğrenme performansına cinsiyetin etkisi

Selective vulnerability of the hippocampal pyramidal neurons to hypothyroidism in male and female rats

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