Anatomical Institute, Department of Biomedicine, University of Basel, Basel, Switzerland.
J Neurosci Res. 2010 Mar;88(4):774-83. doi: 10.1002/jnr.22247.
Purkinje cell loss by excitotoxic damage is a typical finding in many cerebellar diseases. One important aspect of this high sensitivity of Purkinje cells to excitotoxic death might be the enormous size of their dendritic tree, with a high load of excitatory glutamate receptors. We have studied whether reduction in the size of the dendritic tree might confer resistance against excitotoxic death to Purkinje cells. We have grown Purkinje cells in organotypic cerebellar slice cultures under chronic activation of metabotropic glutamate receptors or of protein kinase C. Both treatments strongly reduced dendritic tree size. After this treatment, cells were exposed to the glutamate receptor agonist AMPA, which has a strong excitotoxic effect on Purkinje cells. We found that Purkinje cells with small dendritic trees were as sensitive to AMPA exposure as untreated control cells with large dendritic trees. Immunostaining against vesicular glutamate transporter 1 revealed that the small dendritic trees were densely covered by glutamatergic terminals. Our results indicate that the expansion of the dendritic tree and the total number of AMPA receptors per neuron do not play a major role in determining the susceptibility of Purkinje cells to excitotoxic death.
浦肯野细胞通过兴奋毒性损伤而丢失是许多小脑疾病的典型发现。浦肯野细胞对兴奋毒性死亡高度敏感的一个重要方面可能是其树突的巨大尺寸，具有高负载的兴奋性谷氨酸受体。我们研究了树突大小的减少是否可能赋予浦肯野细胞对兴奋毒性死亡的抗性。我们在器官型小脑切片培养物中培养浦肯野细胞，在代谢型谷氨酸受体或蛋白激酶 C 的慢性激活下进行培养。这两种处理都强烈地减小了树突的大小。在这种处理之后，将细胞暴露于谷氨酸受体激动剂 AMPA 下，该激动剂对浦肯野细胞具有强烈的兴奋毒性作用。我们发现，具有小树突的浦肯野细胞与具有大树突的未经处理的对照细胞一样对 AMPA 暴露敏感。针对囊泡谷氨酸转运体 1 的免疫染色显示，小的树突被谷氨酸能末梢密集覆盖。我们的结果表明，树突的扩展和每个神经元的 AMPA 受体总数在决定浦肯野细胞对兴奋毒性死亡的易感性方面不起主要作用。
