title: Alpha 7 nicotinic acetylcholine receptor agonist GTS-21 mitigates isoflurane-induced cognitive impairment in aged rats.
abstract: BACKGROUND
  Postoperative cognitive dysfunction is increasingly recognized as an important clinical syndrome. Inhalation anesthetics are commonly used during surgery, and it has been proposed that inhalation anesthetics impair cognitive function. However, there are few clinical interventions and treatments available to prevent this disorder. GTS-21, a selective agonist of alpha 7 nicotinic acetylcholine receptor, has been indicated to exert neuroprotective effects in the experimental animal models of neurodegenerative diseases. Therefore, we hypothesized that pretreatment with GTS-21 attenuates isoflurane-induced cognitive decline in aged rats.
  
  
  METHODS
  In the present study, 20-mo-old rats were administered GTS-21 or an equal volume of saline by intraperitoneal injection 30 min before exposure to isoflurane. Then the rats were exposed to 1.3% isoflurane for 4 h. Spatial learning and memory of the rats were assessed at 2 wk after isoflurane exposure. The expression levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the hippocampus and cerebral cortex were determined by enzyme-linked immunosorbent assay. Simultaneously, neuronal apoptosis in the hippocampus was also observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and Nissl staining.
  
  
  RESULTS
  We found that exposure to isoflurane induces learning and memory deficits of old rats. IL-1β in the hippocampus was increased at 4 h after isoflurane exposure. Isoflurane also increased neuroapoptosis in the hippocampus and decreased neuronal density in the CA1 region. And GTS-21 pretreatment effectively alleviated these changes.
  
  
  CONCLUSIONS
  The study demonstrated that pretreatment with α7 nicotinic acetylcholine receptor agonist GTS-21 attenuates isoflurane-induced learning and memory impairment in aged rats.
authors.affiliation: Department of Endocrinology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Department of Anesthesiology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.
authors.forename: Fei-Juan
authors.initials: FJ
authors.lastname: Kong
authors.affiliation: Department of cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.
authors.forename: Hong-Hai
authors.initials: HH
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: xzzzju@126.com.
authors.forename: Jia-Qiang
authors.initials: JQ
authors.lastname: Zhou
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001597:Benzylidene Compounds / Q000494:pharmacology*; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects; D053583:Interleukin-1beta / Q000032:analysis; D007530:Isoflurane / Q000633:toxicity*; D008297:Male; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; D001597:Benzylidene Compounds; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D018722:Nicotinic Agonists; D011725:Pyridines; C088936:3-(2,4-dimethoxybenzylidene)anabaseine; D007530:Isoflurane
keywords: Aged rats; Alpha 7 nicotinic acetylcholine receptor; Apoptosis; Isoflurane; Learning and memory