De March Z, Zuccato C, Giampà C, Patassini S, Bari M, Gasperi V, De Ceballos M L, Bernardi G, Maccarrone M, Cattaneo E, Fusco F R
Laboratory of Neuroanatomy, Santa Lucia Foundation IRCCS at the European Center for Brain research, Via del Fosso Fiorano 64, 00143 Rome, Italy.
Neuroscience. 2008 Mar 27;152(3):734-40. doi: 10.1016/j.neuroscience.2007.11.044. Epub 2007 Dec 8.
An involvement of one particular neurotrophin, namely, the brain-derived neurotrophic factor (BDNF), has been demonstrated in the pathophysiology Huntington's disease. Type-1 cannabinoid (CB1) receptor has been postulated to upregulate BDNF gene transcription. To better understand the relationship between CB1 and BDNF levels in a situation where the striatum is degenerating, we studied, by dual label immunofluorescence, the distribution of CB1 and BDNF in cortical neurons projecting to the striatum in our rat quinolinic acid model of striatal excitotoxicity. We completed our study with quantitative analyses of BDNF protein levels and CB1 binding activity in the cortex. We show that, 2 weeks post lesion, cortical neurons contain more BDNF compared with controls and to earlier time points. Such BDNF up-regulation coincides with a higher binding activity and an increased protein expression of CB1. We suggest that after excitotoxic lesions, CB1 might, at least transiently, upregulate BDNF in the attempt to rescue striatal neurons from degeneration.
一种特定的神经营养因子，即脑源性神经营养因子（BDNF），已被证实在亨廷顿舞蹈病的病理生理学中发挥作用。1型大麻素（CB1）受体被推测可上调BDNF基因转录。为了更好地理解在纹状体发生退化的情况下CB1与BDNF水平之间的关系，我们在大鼠喹啉酸纹状体兴奋毒性模型中，通过双重标记免疫荧光法研究了投射至纹状体的皮质神经元中CB1和BDNF的分布。我们通过对皮质中BDNF蛋白水平和CB1结合活性进行定量分析来完成本研究。我们发现，损伤后2周，与对照组及更早时间点相比，皮质神经元含有更多的BDNF。这种BDNF上调与更高的结合活性以及CB1蛋白表达增加相吻合。我们认为，在兴奋毒性损伤后，CB1可能至少在短期内上调BDNF，试图挽救纹状体神经元免于退化。
