Developmental Hypothyroidism Influences the Development of the Entorhinal-Dentate Gyrus Pathway of Rat Offspring.
Developmental Hypothyroidism Influences the Development of the Entorhinal-Dentate Gyrus Pathway of Rat Offspring.
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DOI：
10.3803/enm.2021.1343
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发表时间：
2022-04
影响因子：
3.4
通讯作者：
Teng, Xiaochun
中科院分区：
文献类型：
--
作者：
Jin, Ting;Wang, Ranran;Peng, Shiqiao;Liu, Xin;Zhang, Hanyi;He, Xue;Teng, Weiping;Teng, Xiaochun
发育性甲状腺功能减退会损害后代的学习和记忆，而学习和记忆依赖于内嗅皮层、海马和新皮层中广泛的神经元回路。内嗅-齿状回通路是记忆回路的主要入口。我们调查是否发育性甲状腺功能减退症损害形态发育的内鼻齿状回通路。我们研究了2-巯基-1-甲基咪唑诱导的发育性甲状腺功能减退反应中内鼻齿状回通路的结构和功能。1，1 ′-双十八烷基-3，3，3 ′，3 ′-四甲基吲哚羰花青高氯酸盐束示踪表明，在甲状腺功能减退的条件下，出生后第2天和第4天，内嗅轴突在到达齿状回外分子层时表现出延迟的生长。在出生后第4天，甲状腺功能减退组的外分子层中的纤维比例显著小于甲状腺功能正常组。在出生后第10天，该通路在外分子层中显示出层特异性分布，类似于甲状腺功能正常组。甲状腺功能低下组内嗅神经轴突投射面积小于甲状腺功能正常组。电生理检查表明，甲状腺功能减退症损害的长时程增强的穿孔和角ammonis 3-角ammonis 1途径。许多排斥性轴突导向分子参与了内鼻齿状回通路的形成。甲状腺功能减退组的促红细胞生成素肝细胞配体A3和脑信号蛋白3A水平高于甲状腺功能正常组。我们证明，发育性甲状腺功能减退症可能会影响内鼻齿状回通路的发展，有助于受损的长时程增强。这些发现提高了我们对记忆功能神经机制的理解。
Developmental hypothyroidism impairs learning and memory in offspring, which depend on extensive neuronal circuits in the entorhinal cortex, together with the hippocampus and neocortex. The entorhinal-dentate gyrus pathway is the main entrance of memory circuits. We investigated whether developmental hypothyroidism impaired the morphological development of the entorhinal-dentate gyrus pathway. We examined the structure and function of the entorhinal-dentate gyrus pathway in response to developmental hypothyroidism induced using 2-mercapto-1-methylimidazole. 1,1´-Dioctadecyl-3,3,3´,3´-tetramethylindocarbocyanine perchlorate tract tracing indicated that entorhinal axons showed delayed growth in reaching the outer molecular layer of the dentate gyrus at postnatal days 2 and 4 in hypothyroid conditions. The proportion of fibers in the outer molecular layer was significantly smaller in the hypothyroid group than in the euthyroid group at postnatal day 4. At postnatal day 10, the pathway showed a layer-specific distribution in the outer molecular layer, similar to the euthyroid group. However, the projected area of entorhinal axons was smaller in the hypothyroid group than in the euthyroid group. An electrophysiological examination showed that hypothyroidism impaired the long-term potentiation of the perforant and the cornu ammonis 3–cornu ammonis 1 pathways. Many repulsive axon guidance molecules were involved in the formation of the entorhinaldentate gyrus pathway. The hypothyroid group had higher levels of erythropoietin-producing hepatocyte ligand A3 and semaphorin 3A than the euthyroid group. We demonstrated that developmental hypothyroidism might influence the development of the entorhinal-dentate gyrus pathway, contributing to impaired long-term potentiation. These findings improve our understanding of neural mechanisms for memory function.