CDNF在多巴胺能神经元变性中对自噬调控的研究

目的探讨CDNF对多巴胺能神经元变性的作用及其对自噬的调控。方法通过蛋白酶体抑制剂Lactacysin诱导PC12细胞变性前和后分别施加200nM的脑源性神经营养因子(cerebral dopamine neurotrophic factor,CDNF),利用MTT法检测PC12细胞生存率、RT-PCR和Western-blotting检测alpha-共核蛋白(synuclein)mRNA和蛋白表达;利用Western-blotting检测p62、Beclin-1和LCI/II蛋白表达。结果经Lactacystin诱导后PC12细胞生存率为0.374±0.086、α-共核蛋白mRNA和蛋白表达分别为5.766±0.052和0.434±0.077,诱导前/后施加200nM的CDNF后PC12细胞生存率分别上升至(0.594±0.121和0.542±0.097)、α-共核蛋白mRNA和蛋白表达分别下降为(0.275±0.047、0.242±0.087和0.325±0.086、0.267±0.075);Beclin-1和p62分别下降为(0.728±0.143、0.235±0.096和0423±0.108、0.258±0.065),而LC3-I/II分别上升为(0.638±0.097和0.601±0.085)。结论 CDNF可能通过负向调控自噬对多巴胺能神经元发挥神经保护和逆转作用。     

Fas基因沉默对帕金森病大鼠脑纹状体多巴胺能神经元凋亡的影响及机制研究

目的 探讨脂肪酸合成酶(Fatty acid synthase,Fas)基因沉默对帕金森病大鼠脑纹状体多巴胺能神经元凋亡的影响及机制.方法 取40只大鼠,30只大鼠脑纹状体注射4μL 6-羟基多巴胺(6-Hydroxydopamine Hydrobromide,6-OHDA)建立帕金森病大鼠模型,剩余10只为假手术组,...     

Molecular regulation of dendritic spine dynamics and their potential impact on synaptic plasticity and neurological diseases

The structure and dynamics of dendritic spines reflect the strength of synapses, which are severely affected in different brain diseases. Therefore, understanding the ultra-structure, molecular signaling mechanism(s) regulating dendritic spine dynamics is crucial. Although, since last century, dynamics of spine have been explored by several investigators in different neurological diseases, but despite countless efforts, a comprehensive understanding of the fundamental etiology and molecular signaling pathways involved in spine pathology is lacking. The purpose of this review is to provide a contextual framework of our current understanding of the molecular mechanisms of dendritic spine signaling, as well as their potential impact on different neurodegenerative and psychiatric diseases, as a format for highlighting some commonalities in function, as well as providing a format for new insights and perspectives into this critical area of research. Additionally, the potential strategies to restore spine structure–function in different diseases are also pointed out. Overall, these informations should help researchers to design new drugs to restore the structure–function of dendritic spine, a “hot site” of synaptic plasticity.