1-甲基-4-苯基-1,2,3,6-四氢吡啶对食蟹猴嗅球多巴胺能神经元的影响

程炜 任振华 关云谦 吴迪 岳峰 李光武*

doi:10.3969/j.issn.0529-1356.2014.03.007

解剖学报 ›› 2014, Vol. 45 ›› Issue (3) : 333-337. DOI: 10.3969/j.issn.0529-1356.2014.03.007

神经生物学

1-甲基-4-苯基-1,2,3,6-四氢吡啶对食蟹猴嗅球多巴胺能神经元的影响

程炜¹ 任振华^{1, 2} 关云谦² 吴迪² 岳峰³ 李光武^1*

作者信息 +

Impact on the dopaminergic neurons of olfactory bulb in cynomolgus monkeys damaged by MPTP

CHENG Wei¹ REN Zhen-hua ^{1, 2} GUAN Yun-qian² WU Di² YUE Feng³ LI Guang-wu ^1*

Author information +

文章历史 +

摘要

目的建立食蟹猴1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)帕金森病系统性模型，探讨嗅球中多巴胺（DA）及多巴胺/cAMP调节磷蛋白（DARPP32）的表达情况。
方法 3只成年健康食蟹猴，静脉注射MPTP，建立帕金森病系统性模型，取出嗅球，切片，免疫组织化学染色DA和DARPP32，摄片并观察DA和DARPP32在食蟹猴嗅球中的分布及表达情况，采用Image Pro-Plus软件，半定量分析模型组和正常组之间DA和DARPP32的表达差异。结果食蟹猴嗅球中DA和DARPP32神经元集中分布于突触小球层，DA神经纤维分布于突触小球层，而DARPP32神经纤维分布于嗅球各层，以突触小球层（GL）和外网状层（EPL）最为密集。MPTP损伤后，与正常对照组比较，DA和DARPP32神经元及神经纤维均减少，以DA神经元及神经纤维减少明显。结论食蟹猴嗅球中DA神经元和神经纤维分布于突触小球层。食蟹猴MPTP帕金森病系统性模型的嗅球DA能神经元和纤维明显减少，可能与帕金森病嗅觉障碍有关。

Abstract

Objective To explore the localization and expression of dopaminergic neurons in olfactory bulb of cynomolgus monkeys damaged by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）. Methods Three adult cynomolgus monkeys were injected with MPTP to induce the damage of dopamine neurons (MPTP group) and three adult cynomolgus monkeys were as a control group. Immunohistochemical staining was performed to examine the localization and expression of dopaminergic neurons in the olfactory bulb in normal and MPTP group monkeys. The numbers of DA-positive and DARPP32-positive cells were counted and the average absorbance was measured in normal and MPTP group. Results DA and DARPP32 positive neurons were concentrated in the glomerular layer (GL) of olfactory bulb. DA positive nerve fibers were distributed in the GL while DARPP32 positive nerve fibers appeared in all layers, and most nerve fibers were in GL and external plexiform layers (EPL). After MPTP injury, compared with the normal control group, DA and DARPP32 positive neurons and nerve fibers decreased in MPTP group and DA neurons and nerve fibers decreased significantly. Conclusions DA neurons and nerve fibers are in the GL of cynomolgus monkey olfactory bulb. DA neurons and fibers are significantly reduced in the olfactory bulb of cynomolgus monkeys damaged by MPTP, which may be associated with the dysosmia in Parkinson’s disease.

导出引用

程炜任振华关云谦吴迪岳峰李光武*. 1-甲基-4-苯基-1,2,3,6-四氢吡啶对食蟹猴嗅球多巴胺能神经元的影响[J]. 解剖学报. 2014, 45(3): 333-337 https://doi.org/10.3969/j.issn.0529-1356.2014.03.007

CHENG Wei REN Zhen-hua GUAN Yun-qian WU Di YUE Feng LI Guang-wu*. Impact on the dopaminergic neurons of olfactory bulb in cynomolgus monkeys damaged by MPTP[J]. Acta Anatomica Sinica. 2014, 45(3): 333-337 https://doi.org/10.3969/j.issn.0529-1356.2014.03.007

参考文献

［1］Doty RL. Olfaction in Parkinson’s disease and related disorders［J］. Neurobiol Dis, 2012, 46(3): 527-552.
［2］Wallace VC, Chaudhuri KR. Unexplained lower limb pain in Parkinson’s disease: a phenotypic variant of “painful Parkinson’s disease”［J］. Parkinsonism Related Disord, 2014,20(1):122-124.
［3］Neikrug AB, Maglione JE, Liu L,et al. Effects of sleep disorders on the non-motor symptoms of Parkinson disease［J］.J Clin Sleep Med,2013,9(11):1119-1129.
［4］Brodoehl S, Klingner C, Volk GF, et al. Decreased olfactory bulb volume in idiopathic Parkinson’s disease detected by 3.0-Tesla magnetic resonance imaging［J］. Mov Disord, 2012, 27(8): 1019-1025.
［5］Haehner A, Boesveldt S, Berendse HW. et al. Prevalence of smell loss in Parkinson’s disease-a multicenter study［J］. Parkinsonism Relat Disord, 2009, 15(7): 490-494.
［6］Belzunegui S, Sebastián W, Garrido-Gil P, et al. The number of dopaminergic cells is increased in the olfactory bulb of monkeys chronically exposed to MPTP［J］. Synapse, 2007, 61(12): 1006-1012.
［7］Bundschuh ST, Zhu P, Schrer YP, et al. Dopaminergic modulation of mitral cells and odor responses in the zebrafish olfactory bulb［J］. J Neurosci, 2012, 32(20): 6830-6840.
［8］Cave J W, Baker H. Dopamine Systems in the Forebrain. Development and Engineering of Dopamine Neurons ［M］. New York: Springer, 2009: 15-35.
［9］Tissingh G, Berendse HW, Bergmans P, et al. Loss of olfaction in de novo and treated Parkinson’s disease: possible implications for early diagnosis［J］. Mov Disord, 2001; 16(1): 41-46.
［10］Huisman E, Uyings HB, Hoogland PV. A 100% increase of dopaminergic in Parkinson’s disease［J］. Mov Disord, 2004, 19(6): 687-692.
［11］Herring B, Shchulze S, Reichman H, et al. A longitudinal study of olfactory function in patients with idiopathic Parkinson’s diease［J］. J Neurol, 2008, 255(3): 367-370.
［12］H?kfelt T, Halasz N, Ljungdahl ?, et al. Histochemical support for a dopaminergic mechanism in the dendrites of certain periglomerular cells in the rat olfactory bulb ［J］. Neurosci Lett, 1975, 1(2): 85-90.
［13］Yuste JE, Echeverry MB, Ros-Bernal F, et al. 7-Nitroindazole down-regulates dopamine/DARPP-32 signaling in neostriatal neurons in a rat model of Parkinson’s disease［J］. Neuropharmacology, 2012,63(7): 1258-1267.
［14］Brown AM, Baucum AJ, Bass MA, et al. Association of protein phosphatase 1 gamma 1 with spinophilin suppresses phosphatase activity in a Parkinson disease model［J］. J Biol Chem, 2008, 283(21): 14286-14294.