Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, 788011, Assam, India.
Department of Zoology, Pandit Deendayal Upadhyaya Adarsha Mahavidyalaya (PDUAM), Eraligool-788723, Karimganj, Assam, India.
Sci Rep. 2017 Dec 20;7(1):17922. doi: 10.1038/s41598-017-17911-z.
There exists an intricate relationship between hypercholesterolemia (elevated plasma cholesterol) and brain functions. The present study aims to understand the impact of hypercholesterolemia on pathological consequences in mouse brain. A chronic mouse model of hypercholesterolemia was induced by giving high-cholesterol diet for 12 weeks. The hypercholesterolemic mice developed cognitive impairment as evident from object recognition memory test. Cholesterol accumulation was observed in four discrete brain regions, such as cortex, striatum, hippocampus and substantia nigra along with significantly damaged blood-brain barrier by hypercholesterolemia. The crucial finding is the loss of acetylcholinesterase activity with mitochondrial dysfunction globally in the brain of hypercholesterolemic mice, which is related to the levels of cholesterol. Moreover, the levels of hydroxyl radical were elevated in the regions of brain where the activity of mitochondrial complexes was found to be reduced. Intriguingly, elevations of inflammatory stress markers in the cholesterol-rich brain regions were observed. As cognitive impairment, diminished brain acetylcholinesterase activity, mitochondrial dysfunctions, and inflammation are the prima facie pathologies of neurodegenerative diseases, the findings impose hypercholesterolemia as potential risk factor towards brain dysfunction.
存在着高胆固醇血症（血浆胆固醇升高）与大脑功能之间的复杂关系。本研究旨在了解高胆固醇血症对小鼠大脑病理后果的影响。通过给予高胆固醇饮食 12 周，诱导出慢性高胆固醇血症小鼠模型。高胆固醇血症小鼠在物体识别记忆测试中表现出认知障碍。胆固醇在四个不同的脑区（如皮质、纹状体、海马和黑质）积累，同时血脑屏障也因高胆固醇血症而受到严重损害。关键的发现是，高胆固醇血症小鼠大脑中的乙酰胆碱酯酶活性和线粒体功能普遍丧失，这与胆固醇水平有关。此外，在发现线粒体复合物活性降低的脑区，羟基自由基的水平升高。有趣的是，在富含胆固醇的脑区观察到炎症应激标志物的升高。由于认知障碍、脑乙酰胆碱酯酶活性降低、线粒体功能障碍和炎症是神经退行性疾病的主要病理学特征，这些发现表明高胆固醇血症是大脑功能障碍的潜在危险因素。
