Evaluation of calcium-sensitive adenylyl cyclase AC1 and AC8 mRNA expression in the anterior cingulate cortex of mice with spared nerve injury neuropathy.
Evaluation of calcium-sensitive adenylyl cyclase AC1 and AC8 mRNA expression in the anterior cingulate cortex of mice with spared nerve injury neuropathy.
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DOI：
10.1016/j.ynpai.2021.100081
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Price TJ
中科院分区：
文献类型：
--
作者：
Shiers S;Elahi H;Hennen S;Price TJ
AC1和AC8在小鼠大脑的许多区域广泛表达，包括海马区、ACC、内侧前额叶皮质和中脑区域，但AC1的表达更高。研究结果表明，AC8在小鼠因幸免神经损伤而导致的焦虑样行为中可能起到了作用。SNI引起对侧ACC NMDAR-2B(NR2B)阳性神经元AC8mRNA表达增加，但不影响AC1mRNA表达。前扣带回皮质(ACC)是啮齿动物和人类疼痛的情绪和情感成分的关键区域。在患者和动物模型中，在神经病理性疼痛状态下都观察到了这一区域的过度活动，从扣带回切开术或用遗传学或药物抑制该区域可以减轻疼痛和焦虑。两个腺苷酸环化酶(AC)AC1和AC8通过在ACC中的作用在调节伤害性和焦虑样行为中发挥重要作用，因为这些酶的遗传和药物靶向分别降低了机械过敏和焦虑样行为。然而，这些AC在ACC中的分布还没有在神经病理性疼痛的背景下进行研究。为了解决这一认识上的差距，我们进行了RNAScope原位杂交，以评估AC1和AC8mRNA在备用神经损伤(SNI)小鼠中的分布。鉴于AC1在神经病理性、炎症性和内脏痛动物模型中在伤害性感受中的关键作用，我们假设AC1在神经损伤后的小鼠的ACC中表达上调。这一假说也是基于数据显示酵母多糖诱导的内脏炎症小鼠的ACC中AC1表达增加。我们发现，AC1和AC8在小鼠大脑的许多区域都有广泛的表达，包括海马区、ACC、内侧前额叶皮质和中脑区，但AC1的表达更高。与我们的假设相反，SNI引起对侧ACC NMDAR-2B(NR2B)阳性神经元AC8mRNA表达增加，但不影响AC1mRNA表达。我们的研究结果表明，Acc中Adcy1mRNA表达的变化不足以解释该AC在小鼠神经损伤后机械超敏反应中的重要作用，并提示AC8在神经损伤后ACC突触变化的调节中具有潜在的未被认识的作用。
AC1 and AC8 are widely expressed in many regions of the mouse brain including the hippocampus, ACC, medial prefrontal cortex and midbrain regions, but AC1 is more highly expressed. Findings suggest a potential role for AC8 in anxiety-like behaviors caused by spared nerve injury in mice. SNI causes an increase in AC8 mRNA expression in NMDAR-2B (Nr2b) positive neurons in the contralateral ACC but does not affect AC1 mRNA expression. The anterior cingulate cortex (ACC) is a critical region of the brain for the emotional and affective components of pain in rodents and humans. Hyperactivity in this region has been observed in neuropathic pain states in both patients and animal models and ablation of this region from cingulotomy, or inhibition with genetics or pharmacology can diminish pain and anxiety. Two adenylyl cyclases (AC), AC1 and AC8 play an important role in regulating nociception and anxiety-like behaviors through an action in the ACC, as genetic and pharmacological targeting of these enzymes reduces mechanical hypersensitivity and anxiety-like behavior, respectively. However, the distribution of these ACs in the ACC has not been studied in the context of neuropathic pain. To address this gap in knowledge, we conducted RNAscope in situ hybridization to assess AC1 and AC8 mRNA distribution in mice with spared nerve injury (SNI). Given the key role of AC1 in nociception in neuropathic, inflammatory and visceral pain animal models, we hypothesized that AC1 would be upregulated in the ACC of mice following nerve injury. This hypothesis was also founded on data showing increased AC1 expression in the ACC of mice with zymosan-induced visceral inflammation. We found that AC1 and AC8 are widely expressed in many regions of the mouse brain including the hippocampus, ACC, medial prefrontal cortex and midbrain regions, but AC1 is more highly expressed. Contrary to our hypothesis, SNI causes an increase in AC8 mRNA expression in NMDAR-2B (Nr2b) positive neurons in the contralateral ACC but does not affect AC1 mRNA expression. Our findings show that changes in Adcy1 mRNA expression in the ACC are insufficient to explain the important role of this AC in mechanical hypersensitivity in mice following nerve injury and suggest a potential unappreciated role of AC8 in regulation of ACC synaptic changes after nerve injury.
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