CDNF protects the nigrostriatal dopamine system and promotes recovery after MPTP treatment in mice.
CDNF protects the nigrostriatal dopamine system and promotes recovery after MPTP treatment in mice.
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DOI：
10.3727/096368911x600948
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发表时间：
2012
影响因子：
3.3
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Airavaara M;Harvey BK;Voutilainen MH;Shen H;Chou J;Lindholm P;Lindahl M;Tuominen RK;Saarma M;Hoffer B;Wang Y
脑多巴胺神经营养因子(CDNF)是新近发现的一种蛋白质，属于进化保守的CDNF/MANF神经营养因子家族。CDNF已被证明可促进体内中脑多巴胺神经元的存活。经过1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)治疗后，多巴胺神经元的变性被很好地描述，该模型的疗效被认为是开发帕金森病治疗的标准标准。MPTP是一种神经毒素，在人类和C57/BL6小鼠中会产生帕金森症状。到目前为止，还没有关于CDNF对MPTP啮齿动物模型中多巴胺神经元存活或功能的影响的报道，这是一个关键的缺口。因此，我们研究了CDNF对注射MPTP后的C57/BL6小鼠黑质纹状体多巴胺系统是否具有神经保护和神经修复作用。我们发现，双侧纹状体注射CDNF，在MPTP前20小时注射，可以改善水平和垂直运动行为。CDNF预处理可增加纹状体和黑质网状部(SNPR)的酪氨酸羟化酶(TH)免疫反应阳性细胞数，并增加致密黑质(SNPC)的TH阳性细胞数。注射MPTP后1周给予CDNF后，小鼠的水平和垂直行为增加，纹状体中的多巴胺纤维密度和SNPC中TH阳性细胞的数量增加。CDNF没有改变任何分析的多巴胺能生物标志物或未经MPTP治疗的动物的运动行为。我们认为，在MPTP模型中，纹状体给予CDNF对黑质纹状体多巴胺系统中TH阳性细胞既有神经保护作用，又有神经修复作用，这支持了基于CDNF治疗帕金森病的发展。
Cerebral dopamine neurotrophic factor (CDNF) is a recently discovered protein, which belongs to the evolutionarily conserved CDNF/MANF family of neurotrophic factors. CDNF has been shown to promote the survival of midbrain dopamine neurons in vivo. The degeneration of dopamine neurons following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -treatment is well characterized and efficacy in this model is considered a standard criterion for development of parkinsonian therapies. MPTP is a neurotoxin, which produces parkinsonian symptoms in humans, and in C57/Bl6 mice. To date, there are no reports about the effects of CDNF on dopamine neuron survival or function in the MPTP rodent model, a critical gap. Therefore, we studied whether CDNF has neuroprotective and neurorestorative properties for the nigrostriatal dopamine system after MPTP injections in C57/Bl6 mice. We found that bilateral striatal CDNF injections, given 20-h before MPTP, improved horizontal and vertical motor behavior. CDNF pre-treatment increased tyrosine hydroxylase (TH)-immunoreactivity in the striatum and in the substantia nigra pars reticulata (SNpr), as well as the number of TH-positive cells in substantia nigra pars compacta (SNpc). Post-treatment with CDNF, given 1 week after MPTP injections, increased horizontal and vertical behavior of mice, as well as dopamine fiber densities in the striatum and the number of TH-positive cells in SNpc. CDNF did not alter any of the analyzed dopaminergic biomarkers or locomotor behavior in MPTP-untreated animals. We conclude that striatal CDNF administration is both neuroprotective and neurorestorative for the TH-positive cells in the nigrostriatal dopamine system in the MPTP model, which supports the development of CDNF-based treatment for Parkinson’s disease.