Brain diabetic neurodegeneration segregates with low intrinsic aerobic capacity.
Brain diabetic neurodegeneration segregates with low intrinsic aerobic capacity.
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DOI：
10.1002/acn3.86
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发表时间：
2014-08
影响因子：
5.3
通讯作者：
Russell, James W.
中科院分区：
文献类型：
--
作者：
Choi, Joungil;Chandrasekaran, Krish;Demarest, Tyler G.;Kristian, Tibor;Xu, Su;Vijaykumar, Kadambari;Dsouza, Kevin Geoffrey;Qi, Nathan R.;Yarowsky, Paul J.;Gallipoli, Rao;Koch, Lauren G.;Fiskum, Gary M.;Britton, Steven L.;Russell, James W.
糖尿病会导致认知障碍，并与年龄相关的神经退行性疾病（包括阿尔茨海默病 (AD)）相关。因此，了解糖尿病引起的脑功能改变对于制定神经退行性疾病的早期干预措施非常重要。低能力跑步（LCR）大鼠肥胖，并表现出类似于人类“糖耐量受损”或代谢综合征的代谢危险因素。我们检查了老年 LCR 大鼠与高容量跑步 (HCR) 大鼠的海马功能。使用质子磁共振波谱和成像、无偏立体学分析和 Y 迷宫检查海马功能。检查了线粒体呼吸链功能以及过度磷酸化 tau 和线粒体转录调节因子水平的变化。老年 LCR 大鼠的谷氨酸、肌醇、牛磺酸和含胆碱化合物的水平显着增加。我们观察到老年 LCR 大鼠海马神经元显着丧失，认知功能受损。老年LCR大鼠的呼吸链功能和活性显着下降。在老年 LCR 大鼠海马中，过度磷酸化的 tau 蛋白在线粒体内积累，过氧化物酶体增殖物激活受体-γ 共激活剂 1α、NAD+ 依赖性蛋白脱乙酰酶 Sirtuin 1 和线粒体转录因子 A 下调。这些数据提供了老年 LCR 大鼠海马神经退行性过程的证据，与人类 AD 等与衰老相关的痴呆疾病中观察到的情况一致。在 LCR 大鼠海马体中观察到的代谢和线粒体异常与已描述的导致糖尿病神经病变的机制相似，并且可能提供认知和代谢功能障碍之间的重要联系。
Diabetes leads to cognitive impairment and is associated with age-related neurodegenerative diseases including Alzheimer's disease (AD). Thus, understanding diabetes-induced alterations in brain function is important for developing early interventions for neurodegeneration. Low-capacity runner (LCR) rats are obese and manifest metabolic risk factors resembling human “impaired glucose tolerance” or metabolic syndrome. We examined hippocampal function in aged LCR rats compared to their high-capacity runner (HCR) rat counterparts. Hippocampal function was examined using proton magnetic resonance spectroscopy and imaging, unbiased stereology analysis, and a Y maze. Changes in the mitochondrial respiratory chain function and levels of hyperphosphorylated tau and mitochondrial transcriptional regulators were examined. The levels of glutamate, myo-inositol, taurine, and choline-containing compounds were significantly increased in the aged LCR rats. We observed a significant loss of hippocampal neurons and impaired cognitive function in aged LCR rats. Respiratory chain function and activity were significantly decreased in the aged LCR rats. Hyperphosphorylated tau was accumulated within mitochondria and peroxisome proliferator-activated receptor-gamma coactivator 1α, the NAD+-dependent protein deacetylase sirtuin 1, and mitochondrial transcription factor A were downregulated in the aged LCR rat hippocampus. These data provide evidence of a neurodegenerative process in the hippocampus of aged LCR rats, consistent with those seen in aged-related dementing illnesses such as AD in humans. The metabolic and mitochondrial abnormalities observed in LCR rat hippocampus are similar to well-described mechanisms that lead to diabetic neuropathy and may provide an important link between cognitive and metabolic dysfunction.
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DOI：
10.1530/joe-12-0356
发表时间：
2013-01
期刊：
The Journal of endocrinology
影响因子：
--
作者：
Hinder LM;Vivekanandan-Giri A;McLean LL;Pennathur S;Feldman EL
通讯作者：
Feldman EL
影响因子：
5.3
作者：
Khan RS;Fonseca-Kelly Z;Callinan C;Zuo L;Sachdeva MM;Shindler KS
通讯作者：
Shindler KS
影响因子：
3.3
作者：
GRUETTER, R
通讯作者：
GRUETTER, R
影响因子：
3.5
作者：
Ekstrand, MI;Falkenberg, M;Larsson, NG
通讯作者：
Larsson, NG
影响因子：
4.8
作者：
Chen, J;Zhou, YG;Li, G
通讯作者：
Li, G