Neuroscience Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Center, via Fleming, 4, 37135, Verona, Italy.
Mol Biol Rep. 2011 Feb;38(2):983-90. doi: 10.1007/s11033-010-0193-0. Epub 2010 Jun 10.
Brain derived neurotrophic factor (BDNF) has been shown to exert multiple actions on neurons. It plays a role in neuronal growth and maintenance and use-dependent plasticity, such as long-term potentiation and learning. This neurotrophin is believed to regulate neuronal plasticity by modifying neuronal excitability and morphology. There is experimental evidence for both an acute and a long-term effect of BDNF on synaptic transmission and structure but the molecular mechanisms underlying these events have not been completely clarified. In order to study the BDNF-induced molecular changes, the set of genes modulated in cultured hippocampal neurons by BDNF treatment was investigated after subchronic treatment with the neurotrophin. Microarray analysis performed with these cells, revealed increased expression of mRNA encoding the neuropeptides neuropeptide Y and somatostatin, and of the secreted peptide VGF (non acronymic), all of which participate in neurotransmission. In addition, the expression of genes apolipoprotein E (ApoE), delta-6 fatty acid desaturase (Fads2) and matrix metalloproteinase 14 (Mmp14), which play a role in neuronal remodelling, was also enhanced. More studies are needed to investigate and confirm the role of these genes in synaptic plasticity, but the results reported in this paper show that microarray analysis of hippocampal cultures can be used to expand our current knowledge of the molecular events triggered by BDNF in the hippocampus.
脑源性神经营养因子 (BDNF) 已被证明对神经元有多种作用。它在神经元的生长和维持以及依赖使用的可塑性(如长时程增强和学习)中发挥作用。这种神经营养因子被认为通过调节神经元兴奋性和形态来调节神经元可塑性。有实验证据表明 BDNF 对突触传递和结构具有急性和长期作用,但这些事件的分子机制尚未完全阐明。为了研究 BDNF 诱导的分子变化,在亚慢性 BDNF 处理后,研究了 BDNF 处理培养的海马神经元中被调节的基因集合。对这些细胞进行微阵列分析,揭示了编码神经肽神经肽 Y 和生长抑素以及分泌肽 VGF(非缩写)的 mRNA 表达增加,所有这些都参与了神经传递。此外,还增强了载脂蛋白 E (ApoE)、delta-6 脂肪酸去饱和酶 (Fads2) 和基质金属蛋白酶 14 (Mmp14) 的基因表达,这些基因在神经元重塑中发挥作用。需要进一步研究以调查和确认这些基因在突触可塑性中的作用,但本文报道的结果表明,海马培养物的微阵列分析可用于扩展我们对 BDNF 在海马中引发的分子事件的现有认识。