Functional and molecular evidence of myelin- and neuroprotection by thyroid hormone administration in experimental allergic encephalomyelitis
Functional and molecular evidence of myelin- and neuroprotection by thyroid hormone administration in experimental allergic encephalomyelitis
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DOI：
10.1111/j.1365-2990.2011.01228.x
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发表时间：
2012-08-01
影响因子：
5
通讯作者：
Calza, L.
中科院分区：
文献类型：
--
作者：
Dell'Acqua, M. L.;Lorenzini, L.;Calza, L.
M.L.戴尔‘Acqua，L.Lorenzini，G.D’Intino，S.Sivilia，P.Pasqualetti，V.Panetta，M.Paradisi，M.M.Filippi，C.Baiguera，M.Pizzi，L.Giardino，P.M.Rossini和L.Calza(2012年)实验性变态反应性脑脊髓炎中髓鞘和神经保护的功能和分子证据38,454470甲状腺激素治疗对髓鞘脱髓鞘和神经保护的功能和分子证据目的：在小鼠和大鼠脱髓鞘模型中的最新数据表明，给予甲状腺激素(TH)对脱髓鞘/再髓鞘平衡有积极的效果。由于轴突病理已被认为是多发性硬化症的早期神经病理事件，而重新髓鞘形成被认为是一种卓越的神经保护策略，在本研究中，我们研究了TH是否改善了神经冲动的传播和保护轴突。方法：对三碘甲腺原氨酸(T3)治疗和未治疗的实验性变态反应性脑脊髓炎(EAE)雌性大鼠尾神经电刺激的体感诱发电位(SEP)进行跟踪观察。T3治疗从免疫后第10天开始(DPI)，脉冲给药持续到研究结束(33DPI)。在基线(8DPI)和每次激素/药物注射后的第二天记录SEP。结果：T3治疗可改善患者的临床和神经生理指标。两组的SEPS潜伏期表现不同，在T3处理的动物中，潜伏期更短，更接近控制值(=更快的脉冲传播)。在24天的DPI上效果明显。在同一组动物中，我们还研究了轴突蛋白，结果表明，给予T3可使EAE动物股薄束中的神经细丝免疫反应正常化和腰髓中tau的过度磷酸化。未发现血浆甲状腺功能亢进症的迹象；此外，经T3治疗后，EAE动物脊髓中TH核受体表达的失调得到纠正。结论：在多发性硬化症动物模型中，补充T3可以保护髓鞘，保护神经传导，保护轴突。
M. L. Dell'Acqua, L. Lorenzini, G. D'Intino, S. Sivilia, P. Pasqualetti, V. Panetta, M. Paradisi, M. M. Filippi, C. Baiguera, M. Pizzi, L. Giardino, P. M. Rossini and L. Calza (2012) Neuropathology and Applied Neurobiology38, 454470 Functional and molecular evidence of myelin- and neuroprotection by thyroid hormone administration in experimental allergic encephalomyelitis Aims: Recent data in mouse and rat demyelination models indicate that administration of thyroid hormone (TH) has a positive effect on the demyelination/remyelination balance. As axonal pathology has been recognized as an early neuropathological event in multiple sclerosis, and remyelination is considered a pre-eminent neuroprotective strategy, in this study we investigated whether TH administration improves nerve impulse propagation and protects axons. Methods: We followed up the somatosensory evoked potentials (SEPs) in triiodothyronine (T3)-treated and untreated experimental allergic encephalomyelitis (EAE) Dark-Agouti female rats during the electrical stimulation of the tail nerve. T3 treatment started on the 10th day post immunization (DPI) and a pulse administration was continued until the end of the study (33 DPI). SEPs were recorded at baseline (8 DPI) and the day after each hormone/ vehicle administration. Results: T3 treatment was associated with better outcome of clinical and neurophysiological parameters. SEPs latencies of the two groups behaved differently, being briefer and closer to control values (=faster impulse propagation) in T3-treated animals. The effect was evident on 24 DPI. In the same groups of animals, we also investigated axonal proteins, showing that T3 administration normalizes neurofilament immunoreactivity in the fasciculus gracilis and tau hyperphosphorylation in the lumbar spinal cord of EAE animals. No sign of plasma hyperthyroidism was found; moreover, the dysregulation of TH nuclear receptor expression observed in the spinal cord of EAE animals was corrected by T3 treatment. Conclusions: T3 supplementation results in myelin sheath protection, nerve conduction preservation and axon protection in this animal model of multiple sclerosis.