title: 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.
abstract: 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.
authors.affiliation: Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Kinzo
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Ken
authors.initials: K
authors.lastname: Tanaka
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Shibahara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyata
authors.forename: Takako
authors.initials: T
authors.lastname: Yokozawa
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D059329:Cholinergic Neurons / Q000187:drug effects / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D013619:Tacrine / Q000494:pharmacology*
chemical_list: D004365:Drugs, Chinese Herbal; C468270:Kangen-karyu; D013619:Tacrine