Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204-5515, USA.
Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
Mol Neurobiol. 2020 Apr;57(4):1930-1937. doi: 10.1007/s12035-019-01865-6. Epub 2020 Jan 3.
Molecular, cellular, and behavioral studies have shown that hypothyroidism impairs hippocampus-dependent learning and memory in adult rats. In these studies, spatial learning and memory were tested in the radial arm water maze (RAWM), which involved locating a hidden platform. In the present study, we investigated the effects of nicotine and hypothyroidism on the CaMKII pathway during learning and memory processes in both spatial and non-spatial memory forms. We used nicotine as a neuroprotective agent. Hypothyroidism was induced by thyroidectomy in adult rats. Rats were trained on the hidden platform (the RAWM for spatial learning and memory) and compared with age-matched rats that were trained on a clearly visible platform system (2 cm above water with no radial arms for non-spatial learning and memory). Nicotine (1 mg/kg twice/day) was administered subcutaneously for 4 weeks. Immediately after training, the protein levels of memory-related signaling molecules were determined in hippocampal area CA1. Western blot analysis revealed a significant increase in calcineurin levels and decreases in P-CaMKII, PKCγ, and calmodulin protein levels in area CA1 of the hippocampi of hypothyroid rats trained on both the visible and hidden platforms. Nicotine treatment normalizes these levels in hypothyroid rats trained on both the visible and hidden platforms. The results suggest that chronic nicotine treatment prevents hypothyroidism-induced suppression of the CaMKII pathway after spatial and non-spatial learning and memory.
分子、细胞和行为研究表明，甲状腺功能减退症会损害成年大鼠海马体依赖的学习和记忆能力。在这些研究中，空间学习和记忆通过放射臂水迷宫（RAWM）进行测试，其中包括定位隐藏平台。在本研究中，我们研究了在空间和非空间记忆形式的学习和记忆过程中，尼古丁和甲状腺功能减退症对 CaMKII 途径的影响。我们使用尼古丁作为神经保护剂。通过甲状腺切除术在成年大鼠中诱导甲状腺功能减退症。大鼠在隐藏平台（用于空间学习和记忆的 RAWM）上接受训练，并与在明显可见平台系统（水面以上 2 厘米，无放射臂，用于非空间学习和记忆）上接受训练的同龄大鼠进行比较。尼古丁（1mg/kg，每日两次）经皮给药 4 周。训练后立即测定海马 CA1 区与记忆相关的信号分子的蛋白水平。Western blot 分析显示，在接受可见和隐藏平台训练的甲状腺功能减退症大鼠的海马 CA1 区，钙调神经磷酸酶水平显著升高，而 P-CaMKII、PKCγ 和钙调蛋白的蛋白水平降低。尼古丁处理可使接受可见和隐藏平台训练的甲状腺功能减退症大鼠的这些水平正常化。结果表明，慢性尼古丁处理可预防空间和非空间学习和记忆后甲状腺功能减退症引起的 CaMKII 途径抑制。
