Bortolotto Vandreza Cardoso, Dahleh Mustafa Munir Mustafa, Marques Luiza Souza, Borstmann Stífani Machado Araujo, Viana Cristini Escobar, Pinheiro Franciane Cabral, Balok Franciéle Romero Machado, Meichtry Luana Barreto, Boeira Silvana Peterini, Guerra Gustavo Petri, Nogueira Cristina Wayne, Prigol Marina
Laboratory of Synthesis, Reactivity, Pharmacological and Toxicological Evaluation of Organochalcogen Compounds, Department of Biochemistry and Molecular Biology, Center of Natural and Exact Sciences - Federal University of Santa Maria, Santa Maria, RS, 97105-900, Brazil; Laboratory of Pharmacological and Toxicological Evaluations Applied to Bioactive Molecules (LaftamBio), Department of Nutrition - Federal University of Pampa, Itaqui, RS, 97650-000, Brazil.
Laboratory of Pharmacological and Toxicological Evaluations Applied to Bioactive Molecules (LaftamBio), Department of Nutrition - Federal University of Pampa, Itaqui, RS, 97650-000, Brazil.
Neuroscience. 2025 Feb 6;566:28-38. doi: 10.1016/j.neuroscience.2024.12.032. Epub 2024 Dec 19.
Hypothyroidism is known to affect memory consolidation, and our prior research highlighted the potential of chrysin as a therapeutic agent to restore cognitive function. The present study aimed to investigate the action mechanism of chrysin on memory deficits in hypothyroid in C57BL/6 female mice. We assessed cognitive flexibility, declarative, working, and aversive memories while analyzing the BDNF/TrkB/AKT/Creb neuroplasticity signaling pathway and synaptic function in the hippocampus and prefrontal cortex. To induce hypothyroidism, mice were exposed to 0.1 % methimazole (MTZ) in the drinking water for 31 days. After confirming low thyroid hormones levels, the mice received either vehicle or chrysin (20 mg/kg) intragastrically once a day for 28 consecutive days. Memory tests were conducted in two separate experiments (experiment 1: Y-maze and reverse Morris water maze; experiment 2: object recognition task and step-down latency), ensuring no memories overlap. Following the tests, the brain samples were collected to analyses ex vivo. Hypothyroid mice exhibited deficits in cognitive flexibility and various memory types, along with altered protein expression related to the BDNF/TrkB/Creb signaling pathway and increased AKT levels in hippocampus and prefrontal cortex. Chrysin treatment effectively reversed these memory deficits, restored cognitive flexibility, and improved protein levels. Our findings suggest that hypothyroidism impairs cognitive flexibility and memory through the BDNF/TrkB/AKT/Creb pathway, which chrysin modulates, operating as a neuroprotector in hypothyroidism. This research sheds light on the potential therapeutic benefits of chrysin for memory-related issues in hypothyroidism.
已知甲状腺功能减退会影响记忆巩固，我们之前的研究强调了白杨素作为一种恢复认知功能的治疗剂的潜力。本研究旨在探讨白杨素对C57BL/6雌性小鼠甲状腺功能减退所致记忆缺陷的作用机制。我们评估了认知灵活性、陈述性记忆、工作记忆和厌恶记忆，同时分析了海马体和前额叶皮质中的BDNF/TrkB/AKT/Creb神经可塑性信号通路和突触功能。为诱导甲状腺功能减退，将小鼠置于含0.1%甲巯咪唑（MTZ）的饮用水中31天。在确认甲状腺激素水平较低后，小鼠连续28天每天一次接受灌胃给予载体或白杨素（20 mg/kg）。在两个独立的实验中进行记忆测试（实验1：Y迷宫和反向莫里斯水迷宫；实验2：物体识别任务和一步下潜伏期），确保记忆不重叠。测试后，收集脑样本进行离体分析。甲状腺功能减退的小鼠表现出认知灵活性和各种记忆类型的缺陷，以及与BDNF/TrkB/Creb信号通路相关的蛋白质表达改变，海马体和前额叶皮质中的AKT水平升高。白杨素治疗有效逆转了这些记忆缺陷，恢复了认知灵活性，并改善了蛋白质水平。我们的研究结果表明，甲状腺功能减退通过BDNF/TrkB/AKT/Creb途径损害认知灵活性和记忆，白杨素可对其进行调节，在甲状腺功能减退中起到神经保护作用。这项研究揭示了白杨素对甲状腺功能减退相关记忆问题的潜在治疗益处。
