Involvement of microtubule integrity in memory impairment caused by colchicine.
In order to fully evaluate the effects of colchicine treatment on learning ability in rats, colchicine was administered, and both Morris water maze (MWM) and step-through type passive avoidance (PA) learning tests were conducted. In both learning tests, infusion of colchicine into the rat dentate gyrus, at two distinct bilateral rostrocaudal locations, potently impaired memory function in a dose-dependent manner (0.01-2.0 microg/site), whereas systemic injection of colchicine (50-300 microg/kg) did not. In the MWM test, memory impairment was observed even at doses where there was no evidence of any histological changes in the dentate granule cells. This suggests that functional deterioration, that is, learning impairment was induced by the dysfunction of microtubules and/or axons, was caused by colchicine. Moreover, ameliorated learning behavior was observed with chronic treatment of beta-estradiol 3-benzoate, which has been suggested to have an important role as an adjuvant treatment for younger Alzheimer's disease (AD), immediately after colchicine infusion (0.3 microg). These results indicate that the animal model accompanying the colchicine-induced functional defect showing early tau pathology, but not neuronal cell degeneration, may well mimic comparatively early stage of AD.
Nakayama
Takahiro
T
BF Research Institute, Inc., c/o National Cardiovascular Center, 7-1, 5-Chome, Fujishiro-dai, Suita, Osaka 565-0873, Japan. Nakayama_Takahiro@takeda.co.jp
Sawada
Tohru
T
D000544:Alzheimer Disease / Q000473:pathology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003078:Colchicine / Q000009:adverse effects*; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006074:Gout Suppressants / Q000009:adverse effects; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D008870:Microtubules / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D006074:Gout Suppressants; C074283:estradiol 3-benzoate; D004958:Estradiol; D003078:Colchicine