Page K J, Besret L, Jain M, Monaghan E M, Dunnett S B, Everitt B J
Medical Research Council Cambridge Centre for Brain Repair, University of Cambridge, UK.
Exp Brain Res. 2000 Jan;130(2):142-50. doi: 10.1007/s002210050016.
Systemic administration of 3-nitropropionic acid (3NPA) in experimental animals produces bilateral striatal lesions similar to those seen in Huntington's disease (HD) caudate and putamen. 3H[-CP55,940 binding to cannabinoid receptors in human basal ganglia nuclei has been shown to be highly susceptible to the earliest pathological changes in the HD brain. In this study, to assess further the suitability of 3NPA-induced striatal lesions as a model for HD neuropathology, we examined the effects of striatal lesions induced by the systemic administration of 3NPA on the binding of 3H[-CP55,940 to pre- and postsynaptic cannabinoid receptors in striatum, globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata and also the effect of 3NPA-induced striatal lesions on the binding of 3H[-DAMGO to mu-opioid receptors in striatal striosomes. Systemic administration of 3NPA induced bilateral and symmetrical lesions in dorsolateral striatum. Within the lesion core, 3H[-CP55,940 and 3H[-DAMGO binding density was reduced to background levels. Beyond the immediate borders of the central core of the 3NPA-induced lesion, striatal binding density was not significantly different from that measured in unlesioned rats. 3H[-CP55,940 binding in globus pallidus, entopeduncular nucleus and substantia nigra in 3NPA-lesioned rats was significantly reduced compared to controls, and the individual decreases were similar for each site. However, these reductions were statistically marginal. These data suggest that, while producing striatal lesions which bear some similarity to those seen in HD, the consequences of 3NPA for striatopallidal and striatonigral efferent projections do not reflect the reported neurodegenerative changes seen in the HD brain.
在实验动物中全身给予3-硝基丙酸（3NPA）会产生双侧纹状体损伤，类似于亨廷顿舞蹈病（HD）尾状核和壳核中所见的损伤。已表明，在人类基底神经节核中，3H-[-CP55,940与大麻素受体的结合对HD脑最早的病理变化高度敏感。在本研究中，为了进一步评估3NPA诱导的纹状体损伤作为HD神经病理学模型的适用性，我们研究了全身给予3NPA诱导的纹状体损伤对3H-[-CP55,940与纹状体、苍白球、内囊核和黑质网状部突触前和突触后大麻素受体结合的影响，以及3NPA诱导的纹状体损伤对3H-[-DAMGO与纹状体纹状体内μ-阿片受体结合的影响。全身给予3NPA诱导双侧背外侧纹状体对称损伤。在损伤核心内，3H-[-CP55,940和3H-[-DAMGO结合密度降至背景水平。在3NPA诱导损伤的中央核心紧邻边界之外，纹状体结合密度与未损伤大鼠中测得的密度无显著差异。与对照组相比，3NPA损伤大鼠苍白球、内囊核和黑质中的3H-[-CP55,940结合显著降低，且每个部位的个体降低相似。然而，这些降低在统计学上不显著。这些数据表明，虽然3NPA产生的纹状体损伤与HD中所见的损伤有一些相似之处，但3NPA对纹状体苍白球和纹状体黑质传出投射的影响并不反映HD脑中报道的神经退行性变化。
