帕金森病MPTP食蟹猴模型嗅球细胞凋亡

陈名宇 程炜 闫莉莉 关云谦 吴迪 岳峰 任振华* 

doi:10.16098/j.issn.0529-1356.2019.01.001

PDF(3333 KB)

解剖学报 ›› 2019, Vol. 50 ›› Issue (1) : 3-7. DOI: 10.16098/j.issn.0529-1356.2019.01.001

神经生物学

帕金森病MPTP食蟹猴模型嗅球细胞凋亡

陈名宇¹程炜¹ 闫莉莉¹ 关云谦² 吴迪²岳峰³ 任振华^1,2*

作者信息 +

Apoptosis of olfactory bulb cells in MPTP cynomolgus monkey model of Parkinson’s dise

CHEN Ming-yu¹ CHENG Wei¹ YAN Li-li¹ GUAN Yun-qian² WU Di² YUE Feng³ REN Zhen-hua ^1,2*

Author information +

文章历史 +

摘要

目的建立1-甲基-4-苯基-1, 2, 3, 6-四氢吡啶（MPTP）帕金森病（PD）模型，探讨模型组嗅球细胞凋亡和胶质细胞增生情况。方法 3只成年健康食蟹猴，静脉注射MPTP建立PD模型，另3只静脉注射生理盐水作为对照。取出嗅球，免疫组织化学染色检测Caspase-3、Bcl-2、离子钙接头蛋白分子1（Iba-1）和胶质纤维酸性蛋白（GFAP）在食蟹猴嗅球中的表达情况，采用Image J v1.8.0软件分析模型组和对照组之间的差异。结果 MPTP损伤后，与对照组相比，模型组嗅球突触小球层Caspase-3阳性细胞数明显增加，而Bcl-2表达减少；与对照组相比，模型组嗅球突触小球层和外网状层的GFAP和Iba-1阳性细胞数增加。结论 MPTP可诱导食蟹猴嗅球突触小球层细胞凋亡，并伴有星形胶质细胞增生和小胶质细胞激活，这可能与帕金森病的功能障碍有关。

Abstract

Objective To explore the apoptosis and the proliferation of glia cells 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 olfactory bulb as MPTP group (model group) and other three adult cynomolgus monkeys as saline group (control group). Immunohistochemical staining was performed to examine the expression of Caspase-3, Bcl-2, ionized calcium binding adaptor molecule-1(Iba-1) and glial fibrillary acidic protein(GFAP) in the olfactory bulb. The numbers of Caspase-3, Bcl-2, Iba1 and GFAP-positive cells were counted and the average absorbance was measured by Image J v1.8.0 in control and MPTP group. Results Compared with the normal control group, Caspase-3-positive cells increased significantly in the glomerular layer (GL) of olfactory bulb, and Bcl-2-positive cells decreased significantly in MPTP group after MPTP injury, and GFAP-positive and Iba-1-positive cells were located in GL and external plexiform layers (EPL). The number of GFAP-positive and Iba-1-positive cells increased in olfactory bulb in the MPTP group. Conclusion MPTP can induce the cell apoptosis, astrocyte and microglial activation in olfactory bulb of cynomolgus monkeys, which may be associated with the dysosmia in Parkinson’s disease.

导出引用

陈名宇程炜闫莉莉关云谦吴迪岳峰任振华. 帕金森病MPTP食蟹猴模型嗅球细胞凋亡[J]. 解剖学报. 2019, 50(1): 3-7 https://doi.org/10.16098/j.issn.0529-1356.2019.01.001

CHEN Ming-yu CHENG Wei YAN Li-li GUAN Yun-qian WU Di YUE Feng REN Zhen-hua. Apoptosis of olfactory bulb cells in MPTP cynomolgus monkey model of Parkinson’s dise [J]. Acta Anatomica Sinica. 2019, 50(1): 3-7 https://doi.org/10.16098/j.issn.0529-1356.2019.01.001

参考文献

［1］Braak H, Sastre M, Bohl JR, et al. Parkinson’s disease: lesions in dorsal horn layer Ⅰ, involvement of parasympathetic and sympathetic pre-and postganglionic neurons［J］. Acta Neuropathol， 2007, 113(4): 421-429.

［2］Kadhim S, Pringsheim T, Le A, et al. Validating screening tools for depression in Parkinson’s disease［J］. Mov Disord， 2018, 33(7): 1184-1186.

［3］Cury RG, Carvalho MJ, Lasteros F, et al. Effects of subthalamic stimulation on olfactory function in Parkinson disease［J］. World Neurosurg， 2018, 114:e559-e564.

［4］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.

［5］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.

［6］Kurlan R, Kim MH, Gash DM. Oral levodopa dose-response study in MPTP-induced hemiparkinsonian monkeys: assessment with a new rating scale for monkey parkinsonism［J］. Mov Disord， 1991, 6(2): 111-118.

［7］Cheng W, Ren ZhH, Guan YQ, et al. Impact on the dopaminergic neurons of olfactory bulb in cynomolgus monkeys damaged by MPTP［J］. Acta Anatomica Sinica, 2014, 45(3): 333-337. (in Chinese)

程炜，任振华，关云谦，等. 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.

［8］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.

［9］Haehner A, Hummel T, Reichmann H. A clinical approach towards smell loss in Parkinson’s disease［J］. J Parkinsons Dis， 2014, 4(2): 189-195.

［10］Sharifi H, Mohajjel NA, Farajnia S, et al. Effect of buspirone, fluoxetine and 8-oh-dpat on striatal expression of Bax, Caspase-3 and Bcl-2 proteins in 6-hydroxydopamine-induced hemi-Parkinsonian rats［J］. Adv Pharm Bull， 2015, 5(4): 491-495.

［11］Liu Y, Guo Y, An S, et al. Targeting Caspase-3 as dual therapeutic benefits by RNAi facilitating brain-targeted nanoparticles in a rat model of Parkinson’s disease［J］. PLoS One， 2013, 8(5): e62905.

［12］Yamada M, Kida K, Amutuhaire W, et al. Gene disruption of caspase-3 prevents MPTP-induced Parkinson’s disease in mice［J］. Biochem Biophys Res Commun， 2010, 402(2): 312-318.

［13］Edlich F. BCL-2 proteins and apoptosis: recent insights and unknowns［J］. Biochem Biophys Res Commun，2018, 500(1): 26-34.

［14］Sridharan S, Mohankumar K, Jeepipalli SP, et al. Neuroprotective effect of valeriana wallichii rhizome extract against the neurotoxin MPTP in C57BL/6 mice［J］. Neurotoxicology， 2015, 51: 172-183.

［15］Ahmed Z, Shaw G, Sharma VP, et al. Actin-binding proteins coronin-1a and IBA-1 are effective microglial markers for immunohistochemistry［J］. J Histochem Cytochem，2007, 55(7): 687-700.

［16] Che Y, Hou L, Sun F, et al. Taurine protects dopaminergic neurons in a mouse Parkinson’s disease model through inhibition of microglial M1 polarization［J］. Cell Death Dis， 2018, 9(4): 435.