title: Translation of BDNF-gene transcripts with short 3' UTR in hippocampal CA1 neurons improves memory formation and enhances synaptic plasticity-relevant signaling pathways.
abstract: 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.
authors.affiliation: The Institutes of Brain Science, The State Key Laboratory of Medical Neurobiology, and The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Man
authors.initials: M
authors.lastname: Wang
authors.affiliation: The Institutes of Brain Science, The State Key Laboratory of Medical Neurobiology, and The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Dongxue
authors.initials: D
authors.lastname: Li
authors.affiliation: The Institutes of Brain Science, The State Key Laboratory of Medical Neurobiology, and The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Di
authors.initials: D
authors.lastname: Yun
authors.affiliation: The Institutes of Brain Science, The State Key Laboratory of Medical Neurobiology, and The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Yinghan
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Molecular and Cellular Neuroscience Department, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Vez
authors.initials: V
authors.lastname: Repunte-Canonigo
authors.affiliation: Molecular and Cellular Neuroscience Department, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Pietro Paolo
authors.initials: PP
authors.lastname: Sanna
authors.affiliation: The Institutes of Brain Science, The State Key Laboratory of Medical Neurobiology, and The Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China. Electronic address: behnish@fudan.edu.cn.
authors.forename: Thomas
authors.initials: T
authors.lastname: Behnisch
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D005239:Fear / Q000502:physiology; D007858:Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D019208:Brain-Derived Neurotrophic Factor
keywords: BNDF; Hippocampus; Learning; Object location memory; Passive avoidance; Synaptic plasticity; Synaptic transmission; Translational medicine; TrkB