proBDNF Negatively Regulates Neuronal Remodeling, Synaptic Transmission, and Synaptic Plasticity in Hippocampus

被引：293

作者：

Yang, Jianmin ^{[1
]}

Harte-Hargrove, Lauren C. ^{[4
]}

Siao, Chia-Jen ^{[1
]}

Marinic, Tina ^{[1
]}

Clarke, Roshelle ^{[1
]}

Ma, Qian ^{[1
]}

Jing, Deqiang ^{[2
]}

LaFrancois, John J. ^{[4
]}

Bath, Kevin G. ^{[6
]}

Mark, Willie ^{[7
]}

Ballon, Douglas ^{[3
]}

Lee, Francis S. ^{[2
]}

Scharfman, Helen E. ^{[4
,5
]}

Hempstead, Barbara L. ^{[1
]}

机构：

[1] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA

[2] Weill Cornell Med Coll, Dept Psychiat, New York, NY 10065 USA

[3] Weill Cornell Med Coll, Dept Radiol, New York, NY 10065 USA

[4] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA

[5] NYU, Langone Med Ctr, New York, NY 10016 USA

[6] Brown Univ, Providence, RI 02912 USA

[7] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA

来源：

CELL REPORTS | 2014年 / 7卷 / 03期

关键词：

LONG-TERM POTENTIATION; DEVELOPING NEUROMUSCULAR SYNAPSES; BDNF KNOCKOUT MICE; NEUROTROPHIC FACTOR; PRO-BDNF; SIGNALING PATHWAYS; PROTEIN-SYNTHESIS; DENDRITIC GROWTH; SELF-AVOIDANCE; MATURE BDNF;

D O I：

10.1016/j.celrep.2014.03.040

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Experience-dependent plasticity shapes postnatal development of neural circuits, but the mechanisms that refine dendritic arbors, remodel spines, and impair synaptic activity are poorly understood. Mature brain-derived neurotrophic factor (BDNF) modulates neuronal morphology and synaptic plasticity, including long-term potentiation (LTP) via TrkB activation. BDNF is initially translated as proBDNF, which binds p75(NTR). In vitro, recombinant proBDNF modulates neuronal structure and alters hippocampal long-term plasticity, but the actions of endogenously expressed proBDNF are unclear. Therefore, we generated a cleavage-resistant probdnf knockin mouse. Our results demonstrate that proBDNF negatively regulates hippocampal dendritic complexity and spine density through p75(NTR). Hippocampal slices from probdnf mice exhibit depressed synaptic transmission, impaired LTP, and enhanced long-term depression (LTD) in area CA1. These results suggest that proBDNF acts in vivo as a biologically active factor that regulates hippocampal structure, synaptic transmission, and plasticity, effects that are distinct from those of mature BDNF.

引用

页码：796 / 806

页数：11

共 53 条

[1]

Quantitative intact specimen magnetic resonance microscopy at 3.0 T [J].

Bath, Kevin G. ;

Voss, Henning U. ;

Jing, Deqiang ;

Anderson, Stewart ;

Hempstead, Barbara ;

Lee, Francis S. ;

Dyke, Jonathan P. ;

Ballon, Douglas J. .

MAGNETIC RESONANCE IMAGING, 2009, 27 (05) :672-680

[2]

Local protein synthesis, actin dynamics, and LTP consolidation [J].

Bramham, Clive R. .

CURRENT OPINION IN NEUROBIOLOGY, 2008, 18 (05) :524-531

[3]

Chen GQ, 1999, J NEUROSCI, V19, P7983

[4]

Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior [J].

Chen, Zhe-Yu ;

Jing, Deqiang ;

Bath, Kevin G. ;

Ieraci, Alessandro ;

Khan, Tanvir ;

Siao, Chia-Jen ;

Herrera, Daniel G. ;

Toth, Miklos ;

Yang, Chingwen ;

McEwen, Bruce S. ;

Hempstead, Barbara L. ;

Lee, Francis S. .

SCIENCE, 2006, 314 (5796) :140-143

[5]

Conner JM, 1997, J NEUROSCI, V17, P2295

[6]

Cowansage Kiriana K, 2010, Curr Mol Pharmacol, V3, P12

[7]

Danzer SC, 2002, J NEUROSCI, V22, P9754

[8]

Neuronal Growth Cone Retraction Relies on Proneurotrophin Receptor Signaling Through Rac [J].

Deinhardt, Katrin ;

Kim, Taeho ;

Spellman, Daniel S. ;

Mains, Richard E. ;

Eipper, Betty A. ;

Neubert, Thomas A. ;

Chao, Moses V. ;

Hempstead, Barbara L. .

SCIENCE SIGNALING, 2011, 4 (202)

[9]

BDNF and its pro-peptide are stored in presynaptic dense core vesicles in brain neurons [J].

Dieni, Sandra ;

Matsumoto, Tomoya ;

Dekkers, Martijn ;

Rauskolb, Stefanie ;

Ionescu, Mihai S. ;

Deogracias, Ruben ;

Gundelfinger, Eckart D. ;

Kojima, Masami ;

Nestel, Sigrun ;

Frotscher, Michael ;

Barde, Yves-Alain .

JOURNAL OF CELL BIOLOGY, 2012, 196 (06) :775-788

[10]

Rac1 is essential in cocaine-induced structural plasticity of nucleus accumbens neurons [J].

Dietz, David M. ;

Sun, Haosheng ;

Lobo, Mary Kay ;

Cahill, Michael E. ;

Chadwick, Benjamin ;

Gao, Virginia ;

Koo, Ja Wook ;

Mazei-Robison, Michelle S. ;

Dias, Caroline ;

Maze, Ian ;

Damez-Werno, Diane ;

Dietz, Karen C. ;

Scobie, Kimberly N. ;

Ferguson, Deveroux ;

Christoffel, Daniel ;

Ohnishi, Yoko ;

Hodes, Georgia E. ;

Zheng, Yi ;

Neve, Rachael L. ;

Hahn, Klaus M. ;

Russo, Scott J. ;

Nestler, Eric J. .

NATURE NEUROSCIENCE, 2012, 15 (06) :891-U117

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