Wang Man, Li Dongxue, Yun Di, Zhuang Yinghan, Repunte-Canonigo Vez, Sanna Pietro Paolo, Behnisch Thomas
The Institutes of Brain Science, The State Key Laboratory of Medical Neurobiology, and The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
Molecular and Cellular Neuroscience Department, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA.
Neurobiol Learn Mem. 2017 Feb;138:121-134. doi: 10.1016/j.nlm.2016.07.004. Epub 2016 Jul 6.
While the brain-derived neurotrophic factor (BDNF) gene and its multiple transcripts have been recognized as a key factor for learning, but the specific involvement of BDNF translated from BDNF transcripts with short-3' untranslated region (short 3' UTR) in learning and memory requires further analysis. In this paper, we present data to show that the transduction of hippocampal CA1 neurons with AAV9-5' UTR-BDNF (short 3' UTR)-IRES-ZsGreen and the subsequent expression of BDNF enhanced the phosphorylation of synaptic plasticity relevant proteins and improved passive avoidance and object location, but not object recognition memory. In addition, BDNF improved the relearning of object location. At higher BDNF overexpression levels, the fear behavior was accompanied with a decline in the passive avoidance memory 24h post training, and with an enhanced fear conditioning performance. In addition, these animals developed spontaneous seizures. Thus, the expression of BDNF in the hippocampal CA1 region has the potential to improve fear and object location memory in wild type mouse strains when the region and expression levels of BDNF are well controlled.
虽然脑源性神经营养因子（BDNF）基因及其多种转录本已被认为是学习的关键因素，但由具有短3'非翻译区（short 3' UTR）的BDNF转录本翻译而来的BDNF在学习和记忆中的具体作用仍需进一步分析。在本文中，我们提供的数据表明，用AAV9-5' UTR-BDNF（short 3' UTR）-IRES-ZsGreen转导海马CA1神经元并随后表达BDNF，可增强与突触可塑性相关蛋白的磷酸化，并改善被动回避和物体定位能力，但对物体识别记忆无影响。此外，BDNF改善了物体定位的再学习能力。在BDNF过表达水平较高时，恐惧行为伴随着训练后24小时被动回避记忆的下降，以及恐惧条件反射表现的增强。此外，这些动物出现了自发性癫痫发作。因此，当BDNF在海马CA1区的表达区域和表达水平得到良好控制时，其表达有可能改善野生型小鼠品系的恐惧和物体定位记忆。
