Oxytocin Elicits Itch Scratching Behavior via Spinal GRP/GRPR System.
Oxytocin Elicits Itch Scratching Behavior via Spinal GRP/GRPR System.
复制标题
催产素通过脊髓 GRP/GRPR 系统引发瘙痒抓挠行为
DOI：
10.3389/fnins.2020.581977
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发表时间：
2020
影响因子：
4.3
通讯作者：
Hao Y
中科院分区：
文献类型：
--
作者：
Guo J;Ba X;Matsuda M;Wei P;Jiang C;Sun W;Xiao L;Xiong D;Liao X;Hao Y
催产素（OT）是一种神经肽，参与调节哺乳动物复杂的社会和性行为，已被提出用于治疗包括疼痛在内的许多精神疾病。有充分的证据表明，OT的集中管理会引起啮齿动物强烈的抓挠和梳理行为。然而，这些行为仅被描述为症状，很少有研究调查其潜在的神经机制。因此，我们重新解决了这个问题，并在本研究中对ot诱导的抓伤行为的脊髓回路进行了分析。我们证明鞘内OT通过激活脊髓OT受体（OTRs）诱导强健但短暂的后爪抓挠行为。结合临床前和临床证据，我们推测ot引起的抓伤可能是一种瘙痒症状。进一步的RNAscope研究显示，近80%的脊髓GRP神经元表达OTRs。OT激活脊髓GRP神经元c-fos mRNA的表达。化学消融GRPR神经元可显著减少鞘内ot诱导的抓伤行为。鉴于GRP/GRPR通路在脊髓瘙痒传递中发挥重要作用，我们提出OT与GRP神经元上表达的OTRs结合，激活GRP/GRPR通路，触发小鼠瘙痒抓痒行为。这些发现为进一步了解ot诱导的行为改变提供了新的证据，这对于开发基于ot的药物来治疗各种精神疾病具有重要意义。
Oxytocin (OT), a neuropeptide involved in the regulation of complex social and sexual behavior in mammals, has been proposed as a treatment for a number of psychiatric disorders including pain. It has been well documented that central administration of OT elicits strong scratching and grooming behaviors in rodents. However, these behaviors were only described as symptoms, few studies have investigated their underlying neural mechanisms. Thus, we readdressed this question and undertook an analysis of spinal circuits underlying OT-induced scratching behavior in the present study. We demonstrated that intrathecal OT induced robust but transient hindpaw scratching behaviors by activating spinal OT receptors (OTRs). Combining the pre-clinical and clinical evidence, we speculated that OT-induced scratching may be an itch symptom. Further RNAscope studies revealed that near 80% spinal GRP neurons expressed OTRs. OT activated the expression of c-fos mRNA in spinal GRP neurons. Chemical ablation of GRPR neurons significantly reduced intrathecal OT-induced scratching behaviors. Given GRP/GRPR pathway plays an important role in spinal itch transmission, we proposed that OT binds to the OTRs expressed on the GRP neurons, and activates GRP/GRPR pathway to trigger itch-scratching behaviors in mice. These findings provide novel evidence relevant for advancing understanding of OT-induced behavioral changes, which will be important for the development of OT-based drugs to treat a variety of psychiatric disorders.
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影响因子：
16.2
作者：
Han Q;Liu D;Convertino M;Wang Z;Jiang C;Kim YH;Luo X;Zhang X;Nackley A;Dokholyan NV;Ji RR
通讯作者：
Ji RR
影响因子：
3.5
作者：
Koshimizu, Taka-aki;Tsujimoto, Gozoh
通讯作者：
Tsujimoto, Gozoh
影响因子：
5.3
作者：
Hurlemann, Rene;Patin, Alexandra;Kendrick, Keith M.
通讯作者：
Kendrick, Keith M.
影响因子：
3
作者：
MEISENBERG, G;SIMMONS, WH
通讯作者：
SIMMONS, WH
接近介导免疫系统调节的催产素调节。
影响因子：
7.3
作者：
Li T;Wang P;Wang SC;Wang YF
通讯作者：
Wang YF