title: Kamikihi-to (KKT) rescues axonal and synaptic degeneration associated with memory impairment in a mouse model of Alzheimer's disease, 5XFAD.
abstract: Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder. Current agents for AD are employed for symptomatic therapy and insufficient to cure. We consider that this is quite necessary for AD treatment and have investigated axon/synapse formation-promoting activity. The aim of this study is to investigate the effects of Kamikihi-to [KKT; traditional Japanese (Kampo) medicine] on memory deficits in an AD model, 5XFAD. KKT (200 mg/kg, p.o.) was administered for 15 days to 5XFAD mice. Object recognition memory was tested in vehicle-treated wild-type and 5XFAD mice and KKT-treated 5XFAD mice. KKT-treated 5XFAD mice showed significant improvement of object recognition memory. KKT treatment significantly reduced the number of amyloid plaques in the frontal cortex and hippocampus. Only inside of amyloid plaques were abnormal structures such as bulb-like axons and swollen presynaptic boutons observed. These degenerated axons and presynaptic terminals were significantly reduced by KKT treatment in the frontal cortex. In primary cortical neurons, KKT treatment significantly increased axon length when applied after Aβ(25-35)-induced axonal atrophy had progressed. In conclusion, KKT improved object recognition memory deficit in an AD model 5XFAD mice. Restoration of degenerated axons and synapses may be associated with the memory recovery by KKT.
authors.affiliation: Division of Biofunctional Evaluation, Research Center for Ethnomedicine, Institute of Natural Medicine, University of Toyama, Japan. chihiro@inm.u-toyama.ac.jp
authors.forename: Chihiro
authors.initials: C
authors.lastname: Tohda
authors.forename: Rie
authors.initials: R
authors.lastname: Nakada
authors.forename: Takuya
authors.initials: T
authors.lastname: Urano
authors.forename: Akira
authors.initials: A
authors.lastname: Okonogi
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Kuboyama
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D020835:Medicine, Kampo / Q000379:methods; D008569:Memory Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013569:Synapses / Q000187:drug effects* / Q000473:pathology
chemical_list: D004365:Drugs, Chinese Herbal; C073747:kamikihi-to