- Thyroid
- Developmental Hypothyroidism Influences the Development of the Entorhinal-Dentate Gyrus Pathway of Rat Offspring
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Ting Jin, Ranran Wang, Shiqiao Peng, Xin Liu, Hanyi Zhang, Xue He, Weiping Teng, Xiaochun Teng
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Endocrinol Metab. 2022;37(2):290-302. Published online April 8, 2022
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DOI: https://doi.org/10.3803/EnM.2021.1343
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 Abstract
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- Background
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.
Methods
We examined the structure and function of the entorhinal-dentate gyrus pathway in response to developmental hypothyroidism induced using 2-mercapto-1-methylimidazole.
Results
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.
Conclusion
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.
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Citations
Citations to this article as recorded by  - Semaphorin 3A Increases in the Plasma of Women with Diminished Ovarian Reserve Who Respond Better to Controlled Ovarian Stimulation
Michela Palese, Gabriella Ferretti, Giuseppe Perruolo, Sara Serafini, Rossana Sirabella, Vincenzo Marrone, Martina De Rosa, Laura Sarno, Ida Strina, Carmela Matrone, Maurizio Guida
Life.2024; 14(3): 358. CrossRef
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