Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 75, Issue 13, Pages 2473-2488Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-017-2742-3
Keywords
Furin; BDNF; CREB; Learning and memory; Long-term potentiation (LTP)
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Funding
- National Natural Science Foundation of China [81622015, 31500821, 81571042, 81220108010] Funding Source: Medline
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Furin is a proprotein convertase implicated in a variety of pathological processes including neurodegenerative diseases. However, the role of furin in neuronal plasticity and learning and memory remains to be elucidated. Here, we report that in brain-specific furin transgenic (Furin-Tg) mice, the dendritic spine density and proliferation of neural progenitor cells were significantly increased. These mice exhibited enhanced long-term potentiation (LTP) and spatial learning and memory performance, without alterations of miniature excitatory/inhibitory postsynaptic currents. In the cortex and hippocampus of Furin-Tg mice, the ratio of mature brain-derived neurotrophic factor (mBDNF) to pro-BDNF, and the activities of extracellular signal-related kinase (ERK) and cAMP response element-binding protein (CREB) were significantly elevated. We also found that hippocampal knockdown of CREB diminished the facilitation of LTP and cognitive function in Furin-Tg mice. Together, our results demonstrate that furin enhances dendritic morphogenesis and learning and memory in transgenic mice, which may be associated with BDNF-ERK-CREB signaling pathway.
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