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

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. © the japanese pharmacological society.