Effects of lithium and valproic acid on BDNF protein and gene expression in an in vitro human neuron-like model of degeneration
Effects of lithium and valproic acid on BDNF protein and gene expression in an in vitro human neuron-like model of degeneration
复制标题
DOI：
10.1177/0269881114529379
复制
发表时间：
2014-10-01
影响因子：
4.1
通讯作者：
Angelucci, Francesco
中科院分区：
文献类型：
--
作者：
Croce, Nicoletta;Mathe, Aleksander A.;Angelucci, Francesco
锂（Li）和丙戊酸（VPA）的共同作用之一是它们能够保护免受兴奋性毒性损伤。神经退行性疾病和神经精神疾病也可能与脑源性神经营养因子（BDNF）的营养支持改变有关，BDNF是中枢神经系统中分布最广泛的神经营养因子。然而，尽管有这些证据，Li-VPA组合对兴奋性毒性损伤后BDNF的影响尚未得到充分研究。我们通过将人神经母细胞瘤细胞系（SH-SY 5 Y）暴露于神经毒性浓度的L-谷氨酸并探索Li-VPA对这些细胞的神经保护作用是否与BDNF蛋白和mRNA水平的变化相关来解决这个问题。结果表明，Li-VPA预孵育24 h和48 h后，谷氨酸对SH-SY 5 Y细胞存活的毒性作用消失，这种神经保护作用与BDNF的合成和mRNA表达增加有关。总之，本研究表明，在SH-SY 5 Y神经母细胞瘤细胞中，Li-VPA对谷氨酸诱导的神经毒性的神经保护作用与BDNF的合成和mRNA表达增加有关。这些数据进一步支持了这两种药物可用于预防和/或治疗谷氨酸相关神经退行性疾病的想法。
One of the common effects of lithium (Li) and valproic acid (VPA) is their ability to protect against excitotoxic insults. Neurodegenerative and neuropsychiatric diseases may be also associated with altered trophic support of brain-derived neurotrophic factor (BDNF), the most widely distributed neurotrophin in the central nervous system. However, despite these evidences, the effect of Li-VPA combination on BDNF after excitoxic insult has been inadequately investigated. We address this issue by exposing a human neuroblastoma cell line (SH-SY5Y) to neurotoxic concentration of L-glutamate and exploring whether the neuroprotective action of Li-VPA on these cells is associated with changes in BDNF protein and mRNA levels. The results showed that pre-incubation of Li-VPA abolished the toxic effect of glutamate on SH-SY5Y cell survival and this neuroprotective effect was associated with increased synthesis and mRNA expression of BDNF after 24 and 48 h of incubation. In conclusion, this study demonstrates that the neuroprotective effects of Li-VPA against glutamate-induced neurotoxicity in SH-SY5Y neuroblastoma cells is associated with increased synthesis and mRNA expression of BDNF. These data further support the idea that these two drugs can be used for prevention and/or treatment of glutamate-related neurodegenerative disorders.