Diabetes-Induced Central Cholinergic Neuronal Loss and Cognitive Deficit Are Attenuated by Tacrine and a Chinese Herbal Prescription, Kangen-Karyu: Elucidation in Type 2 Diabetes db/db Mice
Diabetes-Induced Central Cholinergic Neuronal Loss and Cognitive Deficit Are Attenuated by Tacrine and a Chinese Herbal Prescription, Kangen-Karyu: Elucidation in Type 2 Diabetes db/db Mice
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DOI：
10.1254/jphs.11115fp
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发表时间：
2011-12-01
影响因子：
3.5
通讯作者：
Yokozawa, Takako
中科院分区：
文献类型：
--
作者：
Zhao, Qi;Matsumoto, Kinzo;Yokozawa, Takako
本研究观察了中药复方抗根合剂（KK）对2型糖尿病db/db小鼠认知功能障碍和中枢胆碱能系统的影响。在12周的实验期间，7周龄db/db（Y-db/db）小鼠每天接受测试药物的施用。在18周龄（0-db/db）时，动物进行水迷宫测试。与年龄匹配的对照品系小鼠（O-m/m）相比，溶剂处理的O-db/db小鼠显示出学习和记忆能力受损。KK（100 - 200毫克/公斤，每天）和参考药物他克林（THA：2.5毫克/公斤，每天）改善了O-db/db小鼠的性能，而不影响他们的血糖水平。O-db/db小鼠脑内BDNF mRNA及其蛋白水平低于O-m/m小鼠。O-db/db小鼠海马中中枢胆碱能标记蛋白的表达水平以及内侧隔和基底前脑中胆碱能细胞的数量也显著低于O-m/m小鼠，而Y-m/m和Y-db/db小鼠之间这些因子的表达水平和细胞数量没有显著差异。KK和THA治疗显著逆转了db/db小鼠胆碱能标记物、胆碱乙酰转移酶阳性细胞数和BDNF表达的下调水平。这些结果表明，KK以及THA通过减弱中枢胆碱能系统功能障碍来预防糖尿病诱导的认知缺陷。
We investigated the effect of kangen-karyu (KK), a Chinese herbal prescription, on cognitive deficits and central cholinergic systems of type 2 diabetic db/db mice. Seven-week-old db/db (Y-db/db) mice received daily administration of test drugs during an experimental period of 12 weeks. At 18 weeks of age (O-db/db), the animals underwent the water maze test. Compared with age-matched control strain mice (O-m/m), vehicle-treated O-db/db mice showed impaired learning and memory performance. KK (100 200 mg/kg per day) and the reference drug tacrine (THA: 2.5 mg/kg per day) ameliorated the performance of O-db/db mice without affecting their serum glucose level. O-db/db mice had lower levels of brain-derived neurotrophic factor (BDNF) mRNA and its protein in the brain than O-m/m mice. Expression levels of central cholinergic marker proteins in the hippocampus and the number of cholinergic cells in the medial septum and basal forebrain were also significantly lower in O-db/db than in O-m/m mice, whereas no significant differences in the expression levels of these factors and the cell number were found between Y-m/m and Y-db/db mice. KK and THA treatment significantly reversed the down-regulated levels of cholinergic markers, choline acetyltransferase positive cell number, and BDNF expression in db/db mice. These findings suggest that KK as well as THA prevents diabetes-induced cognitive deficits by attenuating dysfunction of central cholinergic systems.