NeuN is not a reliable marker of dopamine neurons in rat substantia nigra

NeuN is not a reliable marker of dopamine neurons in rat substantia nigra
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DOI:
10.1016/j.neulet.2009.08.023
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发表时间:
2009-10-16
影响因子:
2.5
通讯作者:
Greenamyre, J. Timothy
Greenamyre, J. Timothy
中科院分区:
医学4区
文献类型:
--
作者:
Cannon, Jason R.;Greenamyre, J. Timothy

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神经细胞数量的量化是描述神经退行性疾病模型和神经保护方案的关键终点。免疫组织化学的表型标记,然后是无偏见的体视学通常被用来量化相关的神经元群体。为了在没有细胞死亡的情况下控制表型标记物的丢失,或者确定其他类型的神经元是否丢失,通常需要一个通用的神经元标记物。据报道,脊椎动物神经元特异性核蛋白(Neun)在大多数哺乳动物神经元中都有表达。在帕金森氏病模型中,NeuN已被广泛用于确定是否存在实际的黑质多巴胺神经元丢失或仅仅是酪氨酸羟化酶表达的丢失,这是一个显著的表型标记。到目前为止,NeuN在黑质中的表达作为这样一个标记的定性价值还没有被评估。取对照组大鼠中脑组织切片,进行NeuN和酪氨酸羟化酶染色,并在光镜或共聚焦显微镜下观察。在这里,我们报告了NeuN在大鼠黑质中的表达水平是高度可变的,许多染色微弱的细胞不符合体视学评分标准。此外,很容易发现NeuN表达很少或没有表达的多巴胺神经元。NeuN表达的亚细胞区划也是可变的,许多黑质背侧和腹侧的细胞在胞核和胞浆中都有表达。NeuN在腹侧中脑内的非多巴胺神经元中的表达似乎也要高得多。这种黑质NeuN表达的特征表明,它在黑质中不能作为一个定量的通用神经元标记物。(C)2009爱思唯尔爱尔兰有限公司。保留所有权利。
Quantification of neuronal cell number is a key endpoint in the characterization of neurodegenerative disease models and neuroprotective regimens. Immunohistochemistry for phenotypic markers, followed by unbiased stereology is often used to quantify the relevant neuronal population. To control for loss of phenotypic markers in the absence of cell death, or to determine if other types of neurons are lost, a general neuronal marker is often desired. Vertebrate neuron-specific nuclear protein (NeuN) is reportedly expressed in most mammalian neurons. In Parkinson's disease models, NeuN has been widely used to determine if there is actual nigral dopamine neuron loss or simply loss of tyrosine hydroxylase expression, a prominent phenotypic marker. To date, the qualitative value of NeuN expression as such a marker in the substantia nigra has not been assessed. Midbrain tissue sections from control rats were stained for NeuN and tyrosine hydroxylase and assessed by light or confocal microscopy. Here we report that NeuN expression level in the rat substantia nigra was highly variable, with many faintly stained cells that would not be meet stereological scoring criteria. Additionally, dopamine neurons with little or no NeuN expression were readily identified. Subcellular compartmentalization of NeuN expression was also variable, with many cells dorsal and ventral to the nigra exhibiting expression in both the nucleus and cytoplasm. NeuN expression also appeared to be much higher in non-dopamine neurons within the ventral midbrain. This characterization of nigral NeuN expression suggests that it is not useful as a quantitative general neuronal marker in the substantia nigra. (C) 2009 Elsevier Ireland Ltd. All rights reserved.