title: Dexmedetomidine Acts via the JAK2/STAT3 Pathway to Attenuate Isoflurane-Induced Neurocognitive Deficits in Senile Mice.
abstract: BACKGROUND
  Previous studies showed that isoflurane-induced cognitive deficits could be alleviated by dexmedetomidine in young animal subjects. In the current study, we examine whether dexmedetomidine could also alleviate isoflurane-induced cognitive deficits in senile animals.
  
  
  METHODS
  Senile male C57BL/6 mice (20 months) received dexmedetomidine (50 μg/kg, i.p.) or vehicle 30 minutes prior to isoflurane exposure (1.3% for 4 h). Cognitive function was assessed 19 days later using a 5-day testing regimen with Morris water maze. Some subjects also received pretreatment with α2 adrenoreceptor antagonist atipamezole (250 μg/kg, i.p.), JAK2 inhibitor AG490 (15 mg/kg i.p.) or STAT3 inhibitor WP1066 (40 mg/kg i.p.) 30 minutes prior to dexmedetomidine.
  
  
  RESULTS
  Isoflurane exposure increased and reduced the time spent in the quadrant containing the target platform in training sessions. The number of crossings over the original target quadrant was also decreased. Dexmedotomidine attenuated such effects. Effects of dexmedotomidine were reduced by pretreatment with atipamezole, AG490 and WP1066. Increased phosphorylation of JAK2 and STAT3 in the hippocampus induced by isoflurane was augmented by dexmedetomidine. Effects of dexmedetomidine on JAK2/STAT3 phosphorylation were attenuated by atipamezole, AG490 and WP1066. Isoflurane promoted neuronal apoptosis and increased the expression of cleaved caspase-3 and BAD, and reduced Bcl-2 expression. Attenuation of such effects by dexmedotomidine was partially blocked by atipamezole, AG490 and WP1066.
  
  
  CONCLUSIONS
  Dexmedetomidine could protect against isoflurane-induced spatial learning and memory impairment in senile mice by stimulating the JAK2/STAT3 signaling pathway. Such findings encourage the use of dexmedetomidine in geriatric patients receiving isoflurane anesthesia.
authors: Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Yanna
authors: Y
authors: Si
authors: Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Yuan
authors: Y
authors: Zhang
authors: Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Liu
authors: L
authors: Han
authors: Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Lihai
authors: L
authors: Chen
authors: Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Yajie
authors: Y
authors: Xu
authors: Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Fan
authors: F
authors: Sun
authors: Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, College of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Muhuo
authors: M
authors: Ji
authors: Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, College of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Jianjun
authors: J
authors: Yang
authors: Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
authors: Hongguang
authors: H
authors: Bao
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000517:prevention & control*; D020927:Dexmedetomidine / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D053614:Janus Kinase 2 / Q000378:metabolism*; D051379:Mice; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D020927:Dexmedetomidine; D007530:Isoflurane; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2