鉴定表达vglut3的ltmr募集脊髓回路对瘙痒的抑制作用。

IF 2.9 3区 医学 Q2 NEUROSCIENCES
Xiaojing Su, Liangbiao Wang, Xiaoqing Liu, Yan Zhang
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引用次数: 0

摘要

瘙痒是皮肤病和全身性疾病患者的常见症状,但目前缺乏有效的临床治疗方法。先前的研究表明,水疱性谷氨酸转运蛋白3 (VGLUT3)谱系感觉神经元可能在抑制瘙痒中发挥作用,但脊髓内的电路机制尚不清楚。在这项研究中,我们采用光遗传学技术激活小鼠的vglut3谱系感觉传入神经,并观察到瘙痒源和机械刺激引起的抓挠行为显著减少。此外,取消了用条件场所厌恶(CPA)评价化学痒的厌恶成分。病毒追踪结合电生理记录显示VGLUT3+感觉神经元与脊髓啡肽(SCDYN) /神经肽y表达(SCNPY)神经元之间存在突触连接。进一步的药理学研究表明鞘内注射神经肽Y1受体拮抗剂和kappa阿片受体拮抗剂分别减弱VGLUT3+神经元介导的机械和化学瘙痒的抑制作用。总之,我们的研究结果表明,VGLUT3+感觉神经元通过与脊髓中两类抑制性神经元的相互作用参与瘙痒调节,从而揭示了不同形式的瘙痒管理的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of VGLUT3-expressing LTMRs-recruited spinal circuits for itch inhibition.

Itch is a common symptom among patients suffering dermatological and systemic diseases, yet effective clinical treatments are currently lacking. Previous research has suggested that vesicular glutamate transporter 3 (VGLUT3)-lineage sensory neurons may play a role in inhibiting itch, but the circuit mechanisms within the spinal cord remain unclear. In this study, we employed optogenetic techniques to activate VGLUT3-lineage sensory afferents in mice and observed a significant reduction in scratching behaviors elicited by both pruritogens and mechanical stimuli. Moreover, aversive component of chemical itch assessed by conditioned place aversion (CPA) was abrogated. Viral tracing combined with electrophysiological recordings revealed synaptic connections between VGLUT3+ sensory neurons and spinal dynorphin (SCDYN) /neuropeptide Y-expressing (SCNPY) neurons. Further pharmacological studies indicated that intrathecal injection of antagonists of neuropeptide Y1 receptor and kappa opioid receptor (KOR) separately diminished VGLUT3+ neurons-mediated inhibitory effects on mechanical and chemical itch, respectively. In summary, our findings suggest that VGLUT3+ sensory neurons participate in itch regulation through interactions with two classes of inhibitory neurons in the spinal cord, shedding light on potential therapeutic targets for distinct forms of itch management.

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来源期刊
Molecular Brain
Molecular Brain NEUROSCIENCES-
CiteScore
7.30
自引率
0.00%
发文量
97
审稿时长
>12 weeks
期刊介绍: Molecular Brain is an open access, peer-reviewed journal that considers manuscripts on all aspects of studies on the nervous system at the molecular, cellular, and systems level providing a forum for scientists to communicate their findings. Molecular brain research is a rapidly expanding research field in which integrative approaches at the genetic, molecular, cellular and synaptic levels yield key information about the physiological and pathological brain. These studies involve the use of a wide range of modern techniques in molecular biology, genomics, proteomics, imaging and electrophysiology.
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