Effects of 6-hydroxydopamine on dopaminergic neurons in nigrostriatal system and on behavior of adult mice

XIE Ming-qi CHEN Zhi-chi QI Shuang-shuang WANG Tong-tong ZHANG Peng HUANG Hou-ju ZHOU Peng CUI Huai-rui SUN Chen-you

Acta Anatomica Sinica ›› 2017, Vol. 48 ›› Issue (4) : 361-374.

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Acta Anatomica Sinica ›› 2017, Vol. 48 ›› Issue (4) : 361-374. DOI: 10.16098/j.issn.0529-1356.2017.04.001
Neurobiology

Effects of 6-hydroxydopamine on dopaminergic neurons in nigrostriatal system and on behavior of adult mice

  • XIE Ming-qi1,2 CHEN Zhi-chi1,2 QI Shuang-shuang3 WANG Tong-tong 1,2 ZHANG Peng4  HUANG Hou-ju 2,5 ZHOU Peng 1,2 CUI Huai-rui1  SUN Chen-you1, 2*
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Abstract

Objective To evaluate the proliferation of endogenous neural progenitor cells (NPCs) and its effect on the recovery of injured nigrostiatal system following mesencephalic substantia nigra lesion. Methods The proliferation of NPCs derived from the surrounding regions of the lateral ventricle, the third ventricle (3V) and the cerebral aqueduct (Aq) as well as the midbrain were investigated using immunofluorescent staining on days 3-35 following 6-hydroxydopamine (6-OHDA) injection into the unilateral substantia nigra (SN) of the adult mice. In addition, the proliferation of the SN newborn cells and their differentiation into mature neurons or dopaminergic neurons were explored. Finally, behavioral changes of mice were examined by open field and rotarod tests(n=4-6,each group).
Results The 6-OHDA-induced loss of dopaminergic neurons in the SN significantly increased the numbers of NPCs from the subventricular zone in the surrounding regions of 3V and Aq, which was most obvious on day 7 following 6-OHDA injection. The number of SN new-born cells and new-generated dopaminergic neurons reached to the peak on day 21 following 6-OHDA injection, which possibly resulted in a partial restoration in the lesioned nigrastriatum system and behavioral performance of mice. Conclusion It might be an ideal strategy to deal with Parkinson’s disease by promoting the proliferation and differentiation of endogenous NPCs.

Key words

Parkinson’s disease
/ Substantia nigra / Neural progenitor cell / Dopaminergic neurons / 6-Hydroxydopamine / Immunofluorescence / Mouse

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XIE Ming-qi CHEN Zhi-chi QI Shuang-shuang WANG Tong-tong ZHANG Peng HUANG Hou-ju ZHOU Peng CUI Huai-rui SUN Chen-you. Effects of 6-hydroxydopamine on dopaminergic neurons in nigrostriatal system and on behavior of adult mice[J]. Acta Anatomica Sinica. 2017, 48(4): 361-374 https://doi.org/10.16098/j.issn.0529-1356.2017.04.001

References

[1]Morrison BE. Discovery of nigral dopaminergic neurogenesis in adult mice[J]. Neural Regen Res, 2016, 11(6):878-881.
[2]Parish CL, Beljajeva A, Arenas E, et al. Midbrain dopaminergic neurogenesis and behavioural recovery in a salamander lesion-induced regeneration model.[J]. Development, 2007, 134(15):2881-2887. 
[3] Madhavan L, Daley BF, Paumier KL, et al. Transplantation of subventricular zone neural precursors induces an endogenous precursor cell response in a rat model of Parkinson's disease[J]. J Comp Neurol, 2009, 515(1):102-115. 
[4] Wang JM. Allopregnanolone and neurogenesis in the nigrostriatal tract[J]. Front Cell Neurosci, 2014, 8(8):224.
[5]Liechti R, Ducray AD, Jensen P, et al. Characterization of fetal antigen 1/delta-like 1 homologue expressing cells in the rat nigrostriatal system: effects of a unilateral 6-hydroxydopamine lesion[J]. PLoS One, 2015, 10(2):e116088.
[6]Lee JH, Park HS, Shin JM, et al. Nestin expressing progenitor cells during establishment of the neural retina and its vasculature.[J]. Anat Cell Biol, 2012, 45(1):38-46.
[7]Zhang P, Qi ShSh, Xie MQ, et al. Effect of allopregnanolone on the dopaminergic neurons in the substantia nigra of APPswe /PSEN1 mice [J]. Acta Anatomica Sinica, 2015, 46(3):317-323.(in Chinese)
张鹏,戚双双,谢明琦,等. 别孕烯醇酮对APPswe/PSEN1小鼠黑质多巴胺能神经元的影响[J].解剖学报,2015,46(3):317-323.
[8]Zhao M, Momma S, Delfani K, et al. Evidence for neurogenesis in the adult mammalian substantia nigra.[J]. Proc Natl Acad Sci USA, 2003, 100(13):7925-7930. 
[9]Zhao C, Deng W, Gage FH. Mechanisms and functional implications of adult neurogenesis[J]. Cell, 2008, 132(4):645-660.
[10]H?glinger GU, Rizk P, Muriel MP, et al. Dopamine depletion impairs precursor cell proliferation in Parkinson disease.[J]. Nat Neurosci, 2004, 7(7):726-735.
[11]Tieu K. A guide to neurotoxic animal models of Parkinson's disease.[J]. Cold Spring Harb Perspect Med, 2011, 1(1):a009316.
[12]Zuch CL, Nordstroem VK, Briedrick LA, et al. Time course of degenerative alterations in nigral dopaminergic neurons following a 6-hydroxydopamine lesion ?[J]. J Comp Neurol, 2000, 427(3):440-454. 
[13]Dranovsky A, Picchini AM, Moadel T, et al. Experience dictates stem cell fate in the adult hippocampus.[J]. Neuron, 2011, 70(5):908-923. 
[14]Sun MY, Yetman MJ, Lee TC, et al. Specificity and efficiency of reporter expression in adult neural progenitors vary substantially among nestin-CreER(T2) lines.[J]. J Comp Neurol, 2014, 522(5):1191-1208. 
[15]Zhang P, Xie MQ, Ding YQ, et al. Allopregnanolone enhances the neurogenesis of midbrain dopaminergic neurons in APPswe/PSEN1 mice.[J]. Neuroscience, 2015, 290:214-226. 
[16]Cave JW, Wang M, Baker H. Adult subventricular zone neural stem cells as a potential source of dopaminergic replacement neurons[J]. Front Neurosci, 2014, 8:16. 
[17]Liu H, Guthrie KM. Neuronal replacement in the injured olfactory bulb.[J]. Exp Neurol, 2011, 228(2):270-282. 
[18]Berg DA, Kirkham M, Wang H, et al. Dopamine controls neurogenesis in the adult salamander midbrain in homeostasis and during regeneration of dopamine neurons.[J]. Cell Stem Cell, 2011, 8(4):426-433. 
[19]Hermann A, Maisel M, Wegner F, et al. Multipotent neural stem cells from the adult tegmentum with dopaminergic potential develop essential properties of functional neurons.[J]. Stem Cells, 2006, 24(4):949-964. 
[20]Peng J, Xie L, Jin K, et al. Fibroblast growth factor 2 enhances striatal and nigral neurogenesis in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease.[J]. Neuroscience, 2008, 153(3):664-670. 
[21]Aponso PM, Faull RL, Connor B. Increased progenitor cell proliferation and astrogenesis in the partial progressive 6-hydroxydopamine model of Parkinson’s disease.[J]. Neuroscience, 2008, 151(4):1142-1153. 
[22]Golden JP, Knoten A, Hoshi M, et al. Dopamine-dependent compensation maintains motor behavior in mice with developmental ablation of dopaminergic neurons.[J]. J Neurosci, 2013, 33(43):17095-17107. 
[23]Tieu K. A guide to neurotoxic animal models of Parkinson's disease.[J]. Cold Spring Harb Perspect Med, 2011, 1(1):a009316.
[24]Petzinger GM, Fisher BE, Mcewen S, et al. Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson's disease[J]. Lancet Neurol, 2013, 12(7):716-726. 
[25]Dewan A, Pacifico R, Zhan R, et al. Non-redundant coding of aversive odours in the main olfactory pathway[J]. Nature, 2013, 497(7450):486-489. 
[26]Denny CA, Burghardt NS, Schachter DM, et al. 4- to 6-week-old adult-born hippocampal neurons influence novelty-evoked exploration and contextual fear conditioning. Hippocampus 22: 1188-1201[J]. Hippocampus, 2011, 22(5):1188-1201.
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