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甲状腺激素在嗅觉受体神经元成熟中的重要作用:对发育中大鼠OMP阳性细胞数量和细胞结构的免疫细胞化学研究

Essential role of thyroid hormones in maturation of olfactory receptor neurons: an immunocytochemical study of number and cytoarchitecture of OMP-positive cells in developing rats.

作者信息

Paternostro M A, Meisami E

机构信息

Department of Molecular and Integrative Physiology, University of Illinois, Urbana 61801, USA.

出版信息

Int J Dev Neurosci. 1996 Nov;14(7-8):867-80. doi: 10.1016/s0736-5748(96)00064-0.

Abstract

Neurogenesis and proliferation of olfactory receptor neurons (ORNs) in the olfactory epithelium (OE) are reduced in postnatal hypothyroid rats and upregulated following restoration of thyroid function, leading to compensatory growth and restitution of these deficits [Paternostro M.A. and Meisami E. (1993). Dev. Brain Res. 76, 151-161; Paternostro M.A. and Meisami E. (1994). Dev. Brain Res. 83, 151-162]. To investigate thyroid hormonal role on maturation of ORNs, serial sections of the septal OE from normal newborn, 25- and 90-day-old rats were immunostained for olfactory marker protein (OMP), a marker for mature ORNs, and compared with the same from age-matched hypothyroid rats and those allowed to recover from thyroid deficiency at the time of weaning (day 25). The parameters studied were the localization and distribution of the OMP(+) cells within the OE and their density and total number. Hypothyroidism was induced by adding the reversible goitrogen propylthiouracil (PTU) to the rats' drinking water (1 g/l) from birth to days 25 or 90. Recovery from hypothyroidism was induced by withdrawal of PTU at day 25. The OMP(+) cells occupied a distinct, broad band in the normal rat OE, while in hypothyroid animal, this band was narrow and restricted to OE's apical zones. Recovery resulted in broadening of the OMP(+) cell band and normalized distribution of OMP(+) cells as evident in the 90-day-old recovery animals. In normal control rats, density of OMP(+) cells increased by 2.5- and 1.3-fold during the suckling and post-weaning period (days 25-90), while total numbers of these cells increased by 12- and 3-fold, respectively, during the same age periods. Hypothyroidism decreased the growth in density by 25 and 30%, while total number of OMP(+) neurons were reduced by 40 and 70% in the 25- and 90-day-old animals, respectively. Withdrawal of PTU resulted in marked restoration of these deficits so that, at 90 days, the total number of OMP(+) cells were only 20% less than 90-day-old controls. These results indicate that thyroid hormones are essential for maturation of single ORNs and accretion of new mature ORNs in the OE of suckling and post-weaning rat. Also, the process of maturation and the final number of mature ORNs show remarkable recovery from hypothyroid-induced growth retardation.

摘要

出生后甲状腺功能减退的大鼠,其嗅上皮(OE)中嗅觉受体神经元(ORN)的神经发生和增殖减少,而甲状腺功能恢复后则上调,导致这些缺陷得到代偿性生长和恢复[Paternostro M.A.和Meisami E.(1993年)。《发育脑研究》76卷,第151 - 161页;Paternostro M.A.和Meisami E.(1994年)。《发育脑研究》83卷,第151 - 162页]。为了研究甲状腺激素在ORN成熟过程中的作用,对正常新生大鼠、25日龄和90日龄大鼠的鼻中隔OE连续切片进行免疫染色,以检测嗅觉标记蛋白(OMP),这是成熟ORN的一种标记物,并与年龄匹配的甲状腺功能减退大鼠以及在断奶时(25日龄)从甲状腺功能减退中恢复的大鼠进行比较。研究的参数包括OE内OMP(+)细胞的定位和分布及其密度和总数。通过从出生到25日龄或90日龄在大鼠饮用水中添加可逆性致甲状腺肿物质丙硫氧嘧啶(PTU)(1 g/l)来诱导甲状腺功能减退。在25日龄时停用PTU以诱导从甲状腺功能减退中恢复。OMP(+)细胞在正常大鼠的OE中占据一个独特的宽带,而在甲状腺功能减退的动物中,这个带很窄且局限于OE的顶端区域。恢复导致OMP(+)细胞带变宽,并且OMP(+)细胞分布正常化,这在90日龄的恢复动物中很明显。在正常对照大鼠中,OMP(+)细胞的密度在哺乳和断奶后时期(25 - 90日龄)分别增加了2.5倍和1.3倍,而这些细胞在相同年龄时期的总数分别增加了12倍和3倍。甲状腺功能减退使25日龄和90日龄动物的密度增长分别降低了25%和30%,而OMP(+)神经元的总数分别减少了40%和70%。停用PTU导致这些缺陷明显恢复,以至于在90日龄时,OMP(+)细胞的总数仅比90日龄对照少20%。这些结果表明,甲状腺激素对于哺乳和断奶后大鼠OE中单个ORN的成熟以及新的成熟ORN的增加是必不可少的。此外,成熟过程和成熟ORN的最终数量显示出从甲状腺功能减退引起的生长迟缓中显著恢复。

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