title: Hyperphosphorylated tau in the brains of mice and monkeys with long-term administration of ketamine.
abstract: Ketamine, a non-competitive antagonist at the glutamatergic N-methyl-d-aspartate (NMDA) receptor, might impair memory function of the brain. Loss of memory is also a characteristic of aging and Alzheimer's disease. Hyperphosphorylation of tau is an early event in the aging process and Alzheimer's disease. Therefore, we aimed to find out whether long-term ketmaine administration is related to hyperphosphorylation of tau or not in the brains of mice and monkeys. Results showed that after 6 months' administration of ketamine, in the prefrontal and entorhinal cortical sections of mouse and monkey brains, there were significant increases of positive sites for the hyperphosphorylated tau protein as compared to the control animals receiving no ketamine administration. Furthermore, about 15% of hyperphosphorylated tau positive cells were also positively labeled by terminal dUTP nick end labeling (TUNEL) indicating there might be a relationship between hyperphosphorylation of tau and apoptosis. Therefore, the long-term ketamine toxicity might involve neurodegenerative process similar to that of aging and/or Alzheimer's disease.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
authors.forename: L Y
authors.initials: LY
authors.lastname: Yeung
authors.forename: Maria S M
authors.initials: MS
authors.lastname: Wai
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.forename: Y T
authors.initials: YT
authors.lastname: Mak
authors.forename: W P
authors.initials: WP
authors.lastname: Lam
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: Lu
authors.forename: David T
authors.initials: DT
authors.lastname: Yew
mesh_terms: D000818:Animals; D018728:Entorhinal Cortex / Q000187:drug effects / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D007649:Ketamine / Q000633:toxicity*; D008252:Macaca fascicularis; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D016202:N-Methylaspartate; D007649:Ketamine