Neuronal mechanisms of adenosine A2A receptors in the loss of consciousness induced by propofol general anesthesia with functional magnetic resonance imaging,Journal of Neurochemistry

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Neuronal mechanisms of adenosine A2A receptors in the loss of consciousness induced by propofol general anesthesia with functional magnetic resonance imaging
Journal of Neurochemistry ( IF 4.2 ) Pub Date : 2020-08-12 , DOI: 10.1111/jnc.15146
Lei Chen _{1,

2} , Shuang Li ₂ , Ying Zhou ₁ , Taotao Liu ₃ , Aoling Cai _{2,

4} , Zongze Zhang ₁ , Fuqiang Xu _{2,

4,

5,

6} , Anne Manyande ₇ , Jie Wang _{2,

4} , Mian Peng ₁

Affiliation

Propofol is the most common intravenous anesthetic agent for induction and maintenance of anesthesia, and has been used clinically for more than 30 years. However, the mechanism by which propofol induces loss of consciousness (LOC) remains largely unknown. The adenosine A_2A receptor (A_2AR) has been extensively proven to have an effect on physiological sleep. It is, therefore, important to investigate the role of A_2AR in the induction of LOC using propofol. In the present study, the administration of the highly selective A_2AR agonist (CGS21680) and antagonist (SCH58261) was utilized to investigate the function of A_2AR under general anesthesia induced by propofol by means of animal behavior studies, resting‐state magnetic resonance imaging and c‐Fos immunofluorescence staining approaches. Our results show that CGS21680 significantly prolonged the duration of LOC induced by propofol, increased the c‐Fos expression in nucleus accumbens (NAc) and suppressed the functional connectivity of NAc‐dorsal raphe nucleus (DR) and NAc‐cingulate cortex (CG). However, SCH58261 significantly shortened the duration of LOC induced by propofol, decreased the c‐Fos expression in NAc, increased the c‐Fos expression in DR, and elevated the functional connectivity of NAc‐DR and NAc‐CG. Collectively, our findings demonstrate the important roles played by A_2AR in the LOC induced by propofol and suggest that the neural circuit between NAc‐DR maybe controlled by A_2AR in the mechanism of anesthesia induced by propofol.

中文翻译：

功能性磁共振成像研究丙泊酚全麻诱导腺苷A2A受体失去知觉的神经机制

异丙酚是最常用的诱导和维持麻醉的静脉麻醉剂，已在临床上使用了30多年。但是，丙泊酚诱导意识丧失（LOC）的机制仍然未知。腺苷A _2A受体（A _2A R）已被广泛证明对生理睡眠有影响。因此，重要的是研究A ₂ A R在使用丙泊酚诱导LOC的作用。在本研究中，使用高选择性A _2A R激动剂（CGS21680）和拮抗剂（SCH58261）来研究A _2A的功能丙泊酚通过动物行为研究，静息磁共振成像和c- Fos免疫荧光染色方法在全身麻醉下诱导R. 我们的结果表明CGS21680显着延长了异丙酚诱导的LOC的持续时间，增加了伏伏核（NAc）中c- Fos的表达并抑制了NAc背沟核（DR）和NAc扣带回皮质（CG）的功能连接。但是，SCH58261显着缩短了异丙酚诱导的LOC持续时间，降低了NAc中c- Fos的表达，增加了DR中c- Fos的表达，并提高了NAc-DR和NAc-CG的功能连接性。总的来说，我们的发现证明了A扮演的重要角色丙泊酚诱导的LOC中存在_2A R，提示在丙泊酚诱导的麻醉机制中，NAc-DR之间的神经回路可能受A _2A R的控制。

更新日期：2020-08-12

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