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Cell Rep. 2014 May 8;7(3):796-806. doi: 10.1016/j.celrep.2014.03.040. Epub 2014 Apr 17.

proBDNF negatively regulates neuronal remodeling, synaptic transmission, and synaptic plasticity in hippocampus.

Author information

1
Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
2
The Nathan Kline Institute, Orangeburg, NY 10962, USA.
3
Department of Psychiatry, Weill Cornell Medical College, New York, NY 10065, USA.
4
Brown University, Providence, RI 02912, USA.
5
Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
6
Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA.
7
The Nathan Kline Institute, Orangeburg, NY 10962, USA; New York University Langone Medical Center, New York, NY 10016, USA. Electronic address: hscharfman@nki.rfmh.org.
8
Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: blhempst@med.cornell.edu.

Abstract

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.

PMID:
24746813
PMCID:
PMC4118923
DOI:
10.1016/j.celrep.2014.03.040
[Indexed for MEDLINE]
Free PMC Article

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