小鼠脊髓背角神经元向臂旁核及丘脑中线/板内核群的分支投射
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摘要
目的:观察脊髓背角P物质受体(substance P receptor,SPR)阳性神经元向臂旁核及中线/板内核群的分支投射并为其参与痒觉信息传递提供证据。方法:利用小动物脑立体定位仪向10只8周龄C57BL/6小鼠的臂旁核及丘脑中线/板内核群内分别注射四甲基罗达明(tetramethylrhodamine-dextran,TMR)及荧光金(fluoro-gold,FG),观察小鼠脊髓背角的TMR/FG双标神经元。结合免疫荧光组织化学染色方法观察双标神经元表达SPR和在急性痒模型下表达Fos的情况。结果:脊髓背角I层、脊髓外侧核(lateral spinal nucleus,LSN)及脊髓背角IV～V层均可观察到TMR/FG双标神经元,且部分双标神经元分别表达SPR及Fos蛋白。结论:脊髓背角存在同时向臂旁核及丘脑中线/板内核群发出分支投射的神经元,部分双标神经元表达SPR并参与痒觉信息的传递。
Objective: To observe whether spinal dorsal horn( SDH) substance P receptor( SPR)-immunoreactive(-ir) neurons send collateral projections to the parabrachial nucleus( PBN) and midline/intralaminar thalamic nuclei( MINT) and whether these neurons are activated by itch stimulation. Methods: Ten C57BL/6 mice were stereotactically injected with tetramethylrhodamine-dextran( TMR) into the left PBN and fluoro-gold( FG) into the MINT. Sections of the SDH were used for detecting TMR/FG double-labled neurons and for detecting SPR/TMR/FG or Fos/TMR/FG immunofluorescence histochemical triple stained neurons. Results: TMR/FG double-labeled neurons were observed mainly in the right lamina I,lateral spinal nucleus( LSN) and laminae IV ～ V of the SDH. Some of these collateral projection neurons showed SPR-ir staining. Under the acute itch condition,some of TMR/FG double-labeled neurons were activated and expressed Fos protein. Conclusion: SPR-expressing neurons in SDH send collateral projections to both the PBN and MINT,which might be involved in itch signal transmission.
Objective: To observe whether spinal dorsal horn( SDH) substance P receptor( SPR)-immunoreactive(-ir) neurons send collateral projections to the parabrachial nucleus( PBN) and midline/intralaminar thalamic nuclei( MINT) and whether these neurons are activated by itch stimulation. Methods: Ten C57BL/6 mice were stereotactically injected with tetramethylrhodamine-dextran( TMR) into the left PBN and fluoro-gold( FG) into the MINT. Sections of the SDH were used for detecting TMR/FG double-labled neurons and for detecting SPR/TMR/FG or Fos/TMR/FG immunofluorescence histochemical triple stained neurons. Results: TMR/FG double-labeled neurons were observed mainly in the right lamina I,lateral spinal nucleus( LSN) and laminae IV ～ V of the SDH. Some of these collateral projection neurons showed SPR-ir staining. Under the acute itch condition,some of TMR/FG double-labeled neurons were activated and expressed Fos protein. Conclusion: SPR-expressing neurons in SDH send collateral projections to both the PBN and MINT,which might be involved in itch signal transmission.
引文
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[4]Cameron D,Polgár E,Gutierrez-Mecinas M,et al. The organisation of spinoparabrachial neurons in the mouse[J]. PAIN,2015,156(10):2061-2071. DOI:10. 1097/j. pain. 0000000000000270.
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[6] Ren S,Wang Y,Yue F,et al. The paraventricular thalamus is a critical thalamic area for wakefulness[J]. Science,2018,362:429-434. DOI:10. 1126/science. aat2512.
[7]Zhu Y,Nachtrab G,Keyes PC,et al. Dynamic salience processing in paraventricular thalamus gates associative learning[J]. Science,2018,362:423-429. DOI:10. 1126/science. aat0481.
[8]Liang SH,Yin JB,Sun Y,et al. Collateral projections from the lateral parabrachial nucleus to the paraventricular thalamic nucleus and the central amygdaloid nucleus in the rat[J]. Neurosci Lett,2016,629:245-250. DOI:10. 1016/j. neulet. 2016. 07. 017.
[9]Shyu BC,Vogt BA. Short-term synaptic plasticity in the nociceptive thalamic-anterior cingulate pathway[J]. Mol Pain,2009,5:51.DOI:10. 1186/1744-8069-5-51.
[10] Gauriau C,Bernard J F. A comparative reappraisal of projections from the superficial laminae of the dorsal horn in the rat:the forebrain[J]. J Comp Neurol,2004,468(1):24-56.
[11]Ohanyan T,Schoepke N,Eirefelt S,et al. Role of substance P and its receptor neurokinin 1 in chronic prurigo:A randomized,proof-of concept,controlled trial with topical aprepitant[J]. Acta Derm Venereol,2018,98(1):26-31. DOI:10. 2340/00015555-2780.
[12]Lotts T,Agelopoulos K,Phan N Q,et al. Dihydroavenanthramide D inhibits mast cell degranulation and exhibits anti-inflammatory effects through the activation of neurokinin-1 receptor[J]. Exp Dermatol,2017,26(8):739-742. DOI:10. 1111/exd. 13265.
[13]Akiyama T,Nguyen T,Curtis E,et al. A central role for spinal dorsal horn neurons that express neurokinin-1 receptors in chronic itch[J]. Pain,2015,156(7):1240-1246. DOI:10. 1097/j.pain. 0000000000000172.
[14]Palmiter RD. The parabrachial nucleus:CGRP neurons function as a general alarm[J]. Trends Neurosci,2018,41(5):280-293.DOI:10. 1016/j. tins. 2018. 03. 007.
[15]Jeong K Y,Kang J H. Investigation of the pruritus-induced functional activity in the rat brain using manganese-enhanced MRI[J].J Magn Reson Imaging,2015,42(3):709-716. DOI:10. 1002/jmri. 24832.
[16]Spike RC,Puskar Z,Andrew D,et al. A quantitative and morphological study of projection neurons in lamina I of the rat lumbar spinal cord[J]. Eur J Neurosci,2003,18(9):2433-2448.
[17]Al-Khater KM,Todd AJ. Collateral projections of neurons in laminae I,III,and IV of rat spinal cord to thalamus,periaqueductal gray matter,and lateral parabrachial area[J]. J Comp Neurol,2009,515(6):629-646. DOI:10. 1002/cne. 22081.
[18] Akiyama T,Curtis E,Nguyen T,et al. Anatomical evidence of pruriceptive trigeminothalamic and trigeminoparabrachial projection neurons in mice[J]. J Comp Neurol,2016,524(2):244-256.DOI:10. 1002/cne. 23839.
[19]Bell AM,Gutierrez-Mecinas M,Polgár E,et al. Spinal neurons that contain gastrin-releasing peptide seldom express Fos or phosphorylate extracellular signal-regulated kinases in response to intradermal chloroquine[J]. Mol Pain,2016,12:1-9. DOI:10.1177/1744806916649602.