Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand.
Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai 50200, Thailand.
Exp Gerontol. 2018 Jul 15;108:149-158. doi: 10.1016/j.exger.2018.04.010. Epub 2018 Apr 17.
Our previous study demonstrated that obesity aggravated peripheral insulin resistance and brain dysfunction in the ovariectomized condition. Conversely, the effect of obesity followed by oophorectomy on brain oxidative stress, brain apoptosis, synaptic function and cognitive function, particularly in hippocampal-dependent and hippocampal-independent memory, has not been investigated. Our hypothesis was that oophorectomy aggravated metabolic impairment, brain dysfunction and cognitive impairment in obese rats. Thirty-two female rats were fed with either a normal diet (ND, n = 16) or a high-fat diet (HFD, n = 16) for a total of 20 weeks. At week 13, rats in each group were subdivided into sham and ovariectomized subgroups (n = 8/subgroup). At week 20, all rats were tested for hippocampal-dependent and hippocampal-independent memory by using Morris water maze test (MWM) and Novel objective recognition (NOR) tests, respectively. We found that the obese-insulin resistant condition occurred in sham-HFD-fed rats (HFS), ovariectomized-ND-fed rats (NDO), and ovariectomized-HFD-fed rats (HFO). Increased hippocampal oxidative stress level, increased hippocampal apoptosis, increased hippocampal synaptic dysfunction, decreased hippocampal estrogen level and impaired hippocampal-dependent memory were observed in HFS, NDO, and HFO rats. However, the hippocampal-independent memory, cortical estrogen levels, cortical ROS production, and cortical apoptosis showed no significant difference between groups. These findings suggested that oophorectomy and obesity exclusively impaired hippocampal-dependent memory, possibly via increased hippocampal dysfunction. Nonetheless, oophorectomy did not aggravate these deleterious effects under conditions of obesity.
我们之前的研究表明，肥胖症会加剧去卵巢状态下的外周胰岛素抵抗和大脑功能障碍。相反，肥胖症继而去卵巢对大脑氧化应激、大脑凋亡、突触功能和认知功能的影响，特别是在海马依赖型和海马非依赖型记忆方面，尚未得到研究。我们的假设是，去卵巢会加重肥胖大鼠的代谢损伤、大脑功能障碍和认知障碍。32 只雌性大鼠分别喂食正常饮食（ND，n=16）或高脂肪饮食（HFD，n=16）共 20 周。在第 13 周，每组大鼠又分为假手术和去卵巢亚组（n=8/亚组）。在第 20 周，所有大鼠分别通过 Morris 水迷宫测试（MWM）和新物体识别（NOR）测试评估海马依赖型和海马非依赖型记忆。我们发现，假手术-HFD 喂养大鼠（HFS）、去卵巢-ND 喂养大鼠（NDO）和去卵巢-HFD 喂养大鼠（HFO）出现了肥胖胰岛素抵抗状态。在 HFS、NDO 和 HFO 大鼠中，观察到海马区氧化应激水平升高、海马区凋亡增加、海马区突触功能障碍、海马区雌激素水平降低和海马依赖型记忆受损。然而，在各组大鼠之间，海马非依赖型记忆、皮质雌激素水平、皮质 ROS 生成和皮质凋亡没有显著差异。这些发现表明，去卵巢和肥胖症专门损害了海马依赖型记忆，可能是通过增加海马功能障碍所致。然而，在肥胖症的情况下，去卵巢并没有加重这些有害影响。
