Dataset Information

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 ?g/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 ?2 adrenoreceptor antagonist atipamezole (250 ?g/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.

Conclusion

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.

SUBMITTER: Si Y

PROVIDER: S-EPMC5074497 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dexmedetomidine Acts via the JAK2/STAT3 Pathway to Attenuate Isoflurane-Induced Neurocognitive Deficits in Senile Mice.

Si Yanna Y Zhang Yuan Y Han Liu L Chen Lihai L Xu Yajie Y Sun Fan F Ji Muhuo M Yang Jianjun J Bao Hongguang H

PloS one 20161021 10

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 27768775

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Project description:ObjectiveAt present, studies have confirmed that NDRG4 is specifically expressed in the heart, while its effect on the heart is still unclear. This study is to explore the effect of NDRG4 on cardiomyocyte apoptosis caused by acute myocardial infarction (AMI).MethodsTwenty SD rats were randomly divided into Sham (left anterior descent of heart without ligation) and AMI groups. In this study, coronary artery ligation was used to establish an AMI model, and the AMI model was verified by auxiliary examination and pathological examination. Besides, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) was used to detect the expression level of Bax and Bcl-2 in heart tissues, and NDRG mRNA levels in tissues were also detected. qRT-PCR technology was used to verify the transfection efficiency of NDRG4 in H9C2 cells, and the change of apoptosis level of H9C2 cells was detected by Cell Counting Kit-8 (CCK-8) assay and TUNEL staining; besides, the expression level of apoptosis-related factors was detected by WB and qRT-PCR technology. Simultaneously with the modeling of rats, we injected adenovirus (Ad) into the heart tissue and examined the structural and functional changes of the rat heart. Then, WB technology was used to detect the expression level of the JAK2/STAT3 signaling pathway.ResultsThe heart function and heart structure of rats in the MI group were dramatically worse, and the expression level of NDRG4 was also dramatically reduced. The overexpression of NDRG4 in H9C2 cells can effectively inhibit the ischemia/hypoxia- (I/H-) induced decrease in cell viability and increase in apoptosis rate and inhibit the increase in Bax/Bcl-2 ratio. Moreover, overexpression of NDRG4 in heart tissue can effectively improve the cardiac function and structural destruction caused by MI. In addition, NDRG4 can inhibit JAK2/STAT3 pathway activation.ConclusionThe expression of NDRG4 in the MI tissue of rats was suppressed, while overexpression of NDRG4 by injection of Ad can obviously protect the rat heart. Furthermore, overexpression of NDRG4 in H9C2 cells can effectively inhibit the I/H-induced decrease in cell viability and increase in apoptosis rate, and this may be related to the inhibition of the JAK2/STAT3 signaling pathway.

Dataset Information

Dexmedetomidine Acts via the JAK2/STAT3 Pathway to Attenuate Isoflurane-Induced Neurocognitive Deficits in Senile Mice.

Background

Methods

Results

Conclusion

Publications

Dexmedetomidine Acts via the JAK2/STAT3 Pathway to Attenuate Isoflurane-Induced Neurocognitive Deficits in Senile Mice.

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