CNRS/MNHN UMR 7221-Phyma "Physiologie Moléculaire et Adaptation" Department of "Life Adaptations" Muséum National d'Histoire Naturelle 57, rue Cuvier CP 32, CEDEX 05, 75231 Paris, France.
Institut des Neurosciences Paris-Saclay, Université Paris-Saclay, CNRS, 91400 Saclay, France.
Int J Mol Sci. 2022 Oct 8;23(19):11938. doi: 10.3390/ijms231911938.
Adult-onset hypothyroidism is associated with learning and cognitive dysfunctions, which may be related to alterations in synaptic plasticity. Local reduced levels of thyroid hormones (THs) may impair glia morphology and activity, and promote the increase of pro-inflammatory cytokine levels mainly in the hippocampus. Given that neuroinflammation induces memory impairments, hypothyroidism-related glia dysfunction may participate in brain disorders. Thus, we investigated the mechanisms linking hypothyroidism and neuroinflammation, from a protective perspective. We induced hypothyroidism in adult C57BL/6J and wild-derived WSB/EiJ male mice by a seven-week propylthiouracil (PTU) treatment. We previously showed that WSB/EiJ mice were resistant to high-fat diet (HFD)-induced obesity, showing no neuroinflammatory response through adaptive abilities, unlike C57BL/6J. As PTU and HFD treatments are known to induce comparable inflammatory responses, we hypothesized that WSB/EiJ mice might also be protected against hypothyroidism-induced neuroinflammation. We showed that hypothyroid WSB/EiJ mice depicted no hippocampal neuroinflammatory response and were able to maintain their hippocampal thyroid signalling despite low circulatisng TH levels. In contrast, C57BL/6J mice exhibited disturbed hippocampal TH signalling, accompanied by neuroinflammation and memory impairment. Our results reinforce the preponderance of the hippocampal TH regulatory system over TH circulating levels in the hippocampal glial reactivity.
成人发病型甲状腺功能减退症与学习和认知功能障碍有关，这可能与突触可塑性的改变有关。局部甲状腺激素（THs）水平降低可能会损害神经胶质细胞的形态和活性，并促进主要在海马体中促炎细胞因子水平的增加。鉴于神经炎症会导致记忆障碍，甲状腺功能减退症相关的神经胶质细胞功能障碍可能与大脑疾病有关。因此，我们从保护的角度研究了将甲状腺功能减退症与神经炎症联系起来的机制。我们通过 7 周的丙基硫氧嘧啶（PTU）治疗诱导成年 C57BL/6J 和野生型 WSB/EiJ 雄性小鼠发生甲状腺功能减退症。我们之前表明，WSB/EiJ 小鼠对高脂肪饮食（HFD）诱导的肥胖具有抗性，由于适应能力，它们没有表现出神经炎症反应，与 C57BL/6J 不同。由于已知 PTU 和 HFD 治疗会引起类似的炎症反应，我们假设 WSB/EiJ 小鼠也可能免受甲状腺功能减退症引起的神经炎症的影响。我们表明，甲状腺功能减退症的 WSB/EiJ 小鼠没有海马体神经炎症反应，并且能够维持其海马体甲状腺信号，尽管循环 TH 水平较低。相比之下，C57BL/6J 小鼠表现出海马体 TH 信号紊乱，伴有神经炎症和记忆障碍。我们的研究结果强调了海马体 TH 调节系统相对于循环 TH 水平在海马体神经胶质细胞反应中的优势。
