Department of Endocrinology and Metabolism, Institute of Endocrinology, National Health Commission Key Laboratory of Thyroid Diseases, The First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Endocrinol Metab (Seoul). 2022 Apr;37(2):290-302. doi: 10.3803/EnM.2021.1343. Epub 2022 Apr 8.
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.
发育性甲状腺功能减退症可损害后代的学习和记忆能力，这依赖于内嗅皮层与海马和新皮层之间广泛的神经元回路。内嗅-齿状回通路是记忆回路的主要入口。我们研究了发育性甲状腺功能减退症是否会损害内嗅-齿状回通路的形态发育。
我们使用 2-巯基-1-甲基咪唑来诱导发育性甲状腺功能减退症，以检查内嗅-齿状回通路的结构和功能。
1,1´-二辛基-3,3,3´,3´-四甲基吲哚羰花青-perchlorate 示踪显示，在甲状腺功能减退条件下，内嗅轴突在出生后第 2 天和第 4 天到达齿状回外分子层的生长延迟。在外分子层中，纤维的比例在甲状腺功能减退组明显小于甲状腺功能正常组。在出生后第 10 天，该通路在外分子层表现出层特异性分布，与甲状腺功能正常组相似。然而，内嗅轴突的投射面积在甲状腺功能减退组明显小于甲状腺功能正常组。电生理检查显示，甲状腺功能减退症损害了穿通和角回 3-角回 1 通路的长时程增强。许多排斥性轴突导向分子参与了内嗅-齿状回通路的形成。甲状腺功能减退组的红细胞生成素产生肝细胞配体 A3 和神经纤毛蛋白 3A 的水平高于甲状腺功能正常组。
我们证明了发育性甲状腺功能减退症可能会影响内嗅-齿状回通路的发育，导致长时程增强受损。这些发现增进了我们对记忆功能的神经机制的理解。
