Department of Physiology, School of Medicine, Ardabil University of Medical Sciences, 56189-53141, Ardabil, Iran.
Salari Institute of Cognitive and Behavioral Disorders (SICBD), Karaj, Alborz, Iran; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Physiol Behav. 2022 Oct 1;254:113919. doi: 10.1016/j.physbeh.2022.113919. Epub 2022 Jul 17.
Overweight and obesity are associated with an increased risk of developing dementia and cognitive deficits. Neuroinflammation is one of the most important mechanisms behind cognitive impairment in obese patients. In recent years, the neuroendocrine hormone melatonin has been suggested to have therapeutic effects for memory decline in several neuropsychiatric and neurological conditions. However, the effects of melatonin on cognitive function under obesity conditions still need to be clarified. The purpose of this study was to determine whether melatonin treatment can improve cognitive impairment in obese mice. To this end, male C57BL6 mice were treated with a high-fat diet (HFD) for 20 weeks to induce obesity. The animal received melatonin for 8 weeks. Cognitive functions were evaluated using the Y maze, object recognition test, and the Morris water maze. We measured inflammatory cytokines including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-17A, and brain-derived neurotrophic factor (BDNF) in the hippocampus of obese mice. Our results show that HFD-induced obesity significantly impaired working, spatial and recognition memory by increasing IFN-γ and IL-17A and decreasing BDNF levels in the hippocampus of mice. On the other hand, melatonin treatment effectively improved all cognitive impairments and reduced TNF-α, IFN-γ, and IL-17A and elevated BDNF levels in the hippocampus of obese mice. Taken together, this study suggests that melatonin treatment could have a beneficial role in the treatment of cognitive impairment in obesity.
超重和肥胖与痴呆和认知缺陷风险增加有关。神经炎症是肥胖患者认知障碍背后最重要的机制之一。近年来，神经内分泌激素褪黑素被认为对几种神经精神和神经疾病的记忆减退具有治疗作用。然而，褪黑素对肥胖状态下认知功能的影响仍需阐明。本研究旨在确定褪黑素治疗是否能改善肥胖小鼠的认知障碍。为此，雄性 C57BL6 小鼠接受高脂肪饮食（HFD）治疗 20 周以诱导肥胖。动物接受褪黑素治疗 8 周。使用 Y 迷宫、物体识别测试和 Morris 水迷宫评估认知功能。我们测量了肥胖小鼠海马体中的炎症细胞因子，包括肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ、白细胞介素（IL）-17A 和脑源性神经营养因子（BDNF）。我们的结果表明，HFD 诱导的肥胖通过增加 IFN-γ 和 IL-17A 并降低海马体中的 BDNF 水平，显著损害了工作记忆、空间记忆和识别记忆。另一方面，褪黑素治疗有效改善了所有认知障碍，并降低了肥胖小鼠海马体中的 TNF-α、IFN-γ 和 IL-17A，提高了 BDNF 水平。总之，这项研究表明，褪黑素治疗可能在肥胖导致的认知障碍治疗中发挥有益作用。
