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灵长类动物模型(普通狨猴)中碘缺乏对胎儿大脑发育的影响

Fetal brain development in response to iodine deficiency in a primate model (Callithrix jacchus jacchus).

作者信息

Mano M T, Potter B J, Belling G B, Chavadej J, Hetzel B S

出版信息

J Neurol Sci. 1987 Jul;79(3):287-300. doi: 10.1016/0022-510x(87)90236-x.

Abstract

The common cotton-eared marmoset (Callithrix jacchus jacchus) has been used for the first time as a primate model to study the effects of dietary iodine deficiency on fetal brain development. Paired male and female marmosets were fed a low-iodine diet of maize, peas, meat meal, Torula yeast, maize oil and added vitamins, minerals and amino acids for 6 months before mating. Offspring from first and second pregnancies were compared with offspring from control marmosets fed the same diet but supplemented with iodine. Severe iodine deficiency in the fetus at birth was evident by reduced plasma thyroxine levels, increased plasma thyroid stimulating hormone levels, increased thyroid weight and reduced thyroid iodine content. Thyroid histology revealed hyperplasia, hypertrophy and absence of colloid material in the follicles. Iodine deficiency caused a reduction in the weight of the fetal brain and in particular the cerebellum. Brain cell number was reduced in the cerebellum and brainstem but cell size was reduced in the cerebral hemispheres. Histology of the brain revealed morphological changes in the cerebellum and cerebral hemispheres. In the-cerebellum there was: an increase in the thickness of the external germinal layer indicative of impaired cell acquisition; a decrease in total area; a decrease in molecular layer area; and an increase in Purkinje cell (Pc) linear density due to a reduction in the length of the Pc line. The decrease in molecular layer area and increase in Pc linear density imply diminished ascending and lateral extension of Pc dendrites. Changes in the cerebral hemispheres consisted of an increase in the density of neuronal cell bodies in the granular band and a decrease in synaptic counts in the layer between the pia mater and supragranular band of the visual cortex. Offspring from second pregnancies compared to those from first pregnancies were more severely affected and associated with lower plasma levels of maternal and fetal thyroxine. These findings indicate the importance of maternal and fetal thyroid function in relation to fetal brain development in the primate.

摘要

普通棉耳狨猴(Callithrix jacchus jacchus)首次被用作灵长类动物模型,以研究膳食碘缺乏对胎儿大脑发育的影响。在交配前,将成对的雄性和雌性狨猴喂食低碘饮食,该饮食由玉米、豌豆、肉粉、产朊假丝酵母、玉米油以及添加的维生素、矿物质和氨基酸组成,持续6个月。将第一胎和第二胎的后代与喂食相同饮食但补充了碘的对照狨猴的后代进行比较。出生时胎儿严重碘缺乏表现为血浆甲状腺素水平降低、血浆促甲状腺激素水平升高、甲状腺重量增加和甲状腺碘含量降低。甲状腺组织学显示滤泡增生、肥大且无胶质物质。碘缺乏导致胎儿大脑重量尤其是小脑重量减轻。小脑和脑干中的脑细胞数量减少,但大脑半球中的细胞大小减小。大脑组织学显示小脑和大脑半球有形态变化。在小脑中:外生发层厚度增加,表明细胞获取受损;总面积减小;分子层面积减小;由于浦肯野细胞(Pc)线长度缩短,Pc线密度增加。分子层面积减小和Pc线密度增加意味着Pc树突的上升和侧向延伸减少。大脑半球的变化包括颗粒带中神经元细胞体密度增加以及视觉皮层软脑膜和颗粒上层之间层中的突触计数减少。与第一胎相比,第二胎的后代受影响更严重,且与母体和胎儿甲状腺素的血浆水平较低有关。这些发现表明母体和胎儿甲状腺功能对灵长类动物胎儿大脑发育的重要性。

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