Singer Wibke, Manthey Marie, Panford-Walsh Rama, Matt Lucas, Geisler Hyun-Soon, Passeri Eleonora, Baj Gabriele, Tongiorgi Enrico, Leal Graciano, Duarte Carlos B, Salazar Ivan L, Eckert Philipp, Rohbock Karin, Hu Jing, Strotmann Jörg, Ruth Peter, Zimmermann Ulrike, Rüttiger Lukas, Ott Thomas, Schimmang Thomas, Knipper Marlies
Department of Otolaryngology, Tübingen Hearing Research Centre (THRC), Molecular Physiology of Hearing, University of Tübingen, Tübingen, Germany.
Department of Pharmacology, Institute of Pharmacy, Toxicology and Clinical Pharmacy, University of Tübingen, Tübingen, Germany.
Front Mol Neurosci. 2018 Sep 27;11:325. doi: 10.3389/fnmol.2018.00325. eCollection 2018.
exon-IV and exon-VI transcripts are driven by neuronal activity and are involved in pathologies related to sleep, fear or memory disorders. However, how their differential transcription translates activity changes into long-lasting network changes is elusive. Aiming to trace specifically the network controlled by exon-IV and -VI derived BDNF during activity-dependent plasticity changes, we generated a transgenic reporter mouse for - - ), in which expression of exon-IV and -VI can be visualized by co-expression of CFP and YFP. CFP and YFP expression was differentially activated and targeted in cell lines, primary cultures and BLEV reporter mice without interfering with BDNF protein synthesis. CFP and YFP expression, moreover, overlapped with BDNF protein expression in defined hippocampal neuronal, glial and vascular locations . So far, activity-dependent BDNF cannot be explicitly monitored independent of basal BDNF levels. The BLEV reporter mouse therefore provides a new model, which can be used to test whether stimulus-induced activity-dependent changes in BDNF expression are instrumental for long-lasting plasticity modifications.
外显子-IV和外显子-VI转录本受神经元活动驱动，并参与与睡眠、恐惧或记忆障碍相关的病理过程。然而，它们的差异转录如何将活动变化转化为持久的网络变化仍不清楚。为了在活动依赖性可塑性变化过程中特异性追踪由外显子-IV和-VI衍生的脑源性神经营养因子（BDNF）所控制的网络，我们构建了一种转基因报告小鼠（针对 - - ），其中外显子-IV和-VI的表达可通过共表达青色荧光蛋白（CFP）和黄色荧光蛋白（YFP）来可视化。在细胞系、原代培养物和BLEV报告小鼠中，CFP和YFP的表达被差异激活并靶向，且不干扰BDNF蛋白的合成。此外，CFP和YFP的表达在特定的海马神经元、神经胶质和血管位置与BDNF蛋白表达重叠。到目前为止，无法独立于基础BDNF水平明确监测活动依赖性BDNF。因此，BLEV报告小鼠提供了一种新模型，可用于测试刺激诱导的BDNF表达的活动依赖性变化是否对持久的可塑性修饰起作用。
