Cognitive evaluation of disease-modifying efficacy of galantamine and memantine in the APP23 model.
With increasing knowledge of molecular, biochemical and cellular events causing synaptic dysfunction and neurodegeneration in Alzheimer-diseased brain, preventive treatment strategies are emerging. Neuroprotective capacities have been attributed to galantamine and memantine. The age-dependent cognitive decline in the APP23 model was employed to evaluate disease-modifying efficacy of chronic treatment with both compounds. At age 6 weeks, heterozygous APP23 mice were subcutaneously implanted with osmotic pumps delivering saline, galantamine (1.3 or 2.6 mg/kg/day) or memantine (7.2 or 14.4 mg/kg/day). After 2 months of treatment, a 3-week wash-out period was allowed to prevent bias from sustained symptomatic effects. Subsequently, cognitive evaluation in the Morris water maze commenced. Galantamine low dose significantly improved spatial accuracy during probe trial. Memantine improved acquisition performance (path length) and spatial accuracy during probe trial in a dose-dependent manner. This is the first study reporting disease-modifying efficacy of galantamine and memantine in transgenic mice modeling Alzheimer's disease.
Van Dam
Debby
D
Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Department of Biomedical Sciences, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
De Deyn
Peter Paul
PP
D000544:Alzheimer Disease / Q000188:drug therapy*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005702:Galantamine / Q000627:therapeutic use*; D006801:Humans; D018782:Maze Learning / Q000187:drug effects; D008559:Memantine / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011897:Random Allocation; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
D016564:Amyloid beta-Protein Precursor; D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D005702:Galantamine; D008559:Memantine