Ferreira A A, Pereira M J S, Manhães A C, Barradas P C
Depto. Farmacologia e Psicobiologia, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, 20551-030 Rio de Janeiro, Brazil.
Int J Dev Neurosci. 2007 Apr;25(2):87-94. doi: 10.1016/j.ijdevneu.2006.12.007. Epub 2007 Jan 7.
Thyroid hormone (T3) deficiency impairs the development of the CNS, particularly myelination. We have previously described an increase in the frequency of morphological abnormalities in the central myelin sheath in a hypothyroidism model, which reinforced the hypothesis of a role for T3 in myelin compaction. However, there are no data concerning the cellular distribution of myelin proteins in hypothyroid animals. In the present work, we describe the distribution of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), myelin basic protein (MBP) and proteolipid protein (PLP) throughout the central myelin sheath of a hypothyroidism model. We used euthyroid and hypothyroid adult rats at 90 days of age. In order to induce hypothyroid status, animals received 0.02% methimazol from the 19th gestation day onwards. After perfusion with a fixative mixture, small pieces of corpus callosum were obtained, dehydrated and embedded in LR White resin. Ultrathin sections were immunoreacted, using specific antibodies revealed by a secondary antibody coupled to colloidal gold particles of 10nm. Gold particle density per region of myelin sheath for each one of these proteins was obtained. In normal animals, CNPase, PLP and MBP were identified in sites that had already been described in previous studies. In hypothyroid animals, CNPase was identified in the region corresponding to compact lamellae, which normally does not contain this protein, while, in this same region, PLP and MBP immunolabeling were decreased. These results suggest that thyroid hormone deficiency impairs the distribution of the major oligodendrocyte/myelin markers. This effect may justify the reduction in myelin sheath compaction previously demonstrated in a similar model of hypothyroidism.
甲状腺激素(T3)缺乏会损害中枢神经系统的发育,尤其是髓鞘形成。我们之前曾描述过,在甲状腺功能减退模型中,中枢髓鞘的形态异常频率增加,这强化了T3在髓鞘压实中起作用的假说。然而,关于甲状腺功能减退动物中髓鞘蛋白的细胞分布尚无数据。在本研究中,我们描述了2',3'-环核苷酸3'-磷酸二酯酶(CNPase)、髓鞘碱性蛋白(MBP)和蛋白脂蛋白(PLP)在甲状腺功能减退模型中枢髓鞘中的分布情况。我们使用了90日龄的成年甲状腺功能正常和甲状腺功能减退大鼠。为了诱导甲状腺功能减退状态,从妊娠第19天起,给动物喂食0.02%的甲巯咪唑。用固定剂混合物灌注后,获取小块胼胝体,脱水并包埋在LR White树脂中。超薄切片进行免疫反应,使用与10nm胶体金颗粒偶联的二抗所识别的特异性抗体。获得了这些蛋白质在髓鞘每个区域的金颗粒密度。在正常动物中,CNPase、PLP和MBP在先前研究中已描述的部位被识别。在甲状腺功能减退动物中,在通常不含该蛋白的致密板层区域识别到了CNPase,而在同一区域,PLP和MBP的免疫标记减少。这些结果表明,甲状腺激素缺乏会损害主要少突胶质细胞/髓鞘标志物的分布。这种效应可能解释了先前在类似甲状腺功能减退模型中所证明的髓鞘压实减少的现象。