Nicotine exacerbates tau phosphorylation and cognitive impairment induced by amyloid-beta 25-35 in rats.
Nicotine was reported to reduce the plaque burden and could be used as a possible anti-Alzheimer's disease agent. However, the effect of nicotine on memory and tau pathology in Alzheimer's disease has been less studied. The present study investigated the effect of nicotine on tau phosphorylation and cognitive impairment induced by hippocampus injections of amyloid-beta (Abeta) 25-35. Rats were treated with nicotine hydrogen tartrate salt dissolved in normal saline by subcutaneous injection twice per day for 14 days. The age and gender matched rats treated with same amount of normal saline were used as the control. Morris water maze was used to detect the cognitive impairment induced by Abeta25-35. Compared to the sham-operated rats, Abeta25-35 injection significantly prolonged the mean escape latency in vehicle-treated rats in the Morris water maze test and increased the number of tau(pS202) and tau(pT231) immunoreactive cells. The data show that nicotine (1mg/kg in base weight) treatment significantly exacerbates cognitive impairment and tau phosphorylation at Ser-202 and Thr-231 in the hippocampus compared with Abeta25-35 injection groups in the Abeta rat model of Alzheimer's disease. The use of nicotine for treatment of Alzheimer's disease should be reassessed.
Deng
Juan
J
Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China.
Shen
Cheng
C
Wang
Yan-Jiang
YJ
Zhang
Meng
M
Li
Jing
J
Xu
Zhi-Qiang
ZQ
Gao
Chang-Yue
CY
Fang
Chuan-Qing
CQ
Zhou
Hua-Dong
HD
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D016875:tau Proteins; D009538:Nicotine