Definition of a Bidirectional Activity-Dependent Pathway Involving BDNF and Narp

Abigail Mariga; Juliane Glaser; Leo Mathias; Desheng Xu; Meifang Xiao; Paul Worley; Ipe Ninan; Moses V Chao

doi:10.1016/j.celrep.2015.10.064

Definition of a Bidirectional Activity-Dependent Pathway Involving BDNF and Narp

Cell Rep. 2015 Dec 1;13(9):1747-56. doi: 10.1016/j.celrep.2015.10.064. Epub 2015 Nov 19.

Authors

Abigail Mariga¹, Juliane Glaser², Leo Mathias³, Desheng Xu⁴, Meifang Xiao⁴, Paul Worley⁴, Ipe Ninan⁵, Moses V Chao⁶

Affiliations

¹ Cell and Molecular Biology Program, New York University, Langone Medical Center, New York, NY 10016, USA; Department of Cell Biology, Skirball Institute of Bimolecular Medicine, NYU Langone Medical Center, New York, NY 10016, USA.
² Unit of Genetics and Biology of Development, Institut Curie, 75005 Paris, France.
³ Magistère de Génétique Graduate Program, Université Paris Diderot, 75013 Paris, France.
⁴ Departments of Neuroscience and Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁵ Department of Psychiatry, New York, University, Langone Medical Center, New York, New YorkNY 10016, USA.
⁶ Department of Cell Biology, Skirball Institute of Bimolecular Medicine, NYU Langone Medical Center, New York, NY 10016, USA; Department of Psychiatry, New York, University, Langone Medical Center, New York, New YorkNY 10016, USA; Department of Physiology and Neuroscience, New York, University, Langone Medical Center, New York, New YorkNY 10016, USA. Electronic address: moses.chao@med.nyu.edu.

Abstract

One of the cardinal features of neural development and adult plasticity is the contribution of activity-dependent signaling pathways. However, the interrelationships between different activity-dependent genes are not well understood. The immediate early gene neuronal-activity-regulated pentraxin (NPTX2 or Narp) encodes a protein that has been associated with excitatory synaptogenesis, AMPA receptor aggregation, and the onset of critical periods. Here, we show that Narp is a direct transcriptional target of brain-derived neurotrophic factor (BDNF), another highly regulated activity-dependent gene involved in synaptic plasticity. Unexpectedly, Narp is bidirectionally regulated by BDNF. Acute BDNF withdrawal results in downregulation of Narp, whereas transcription of Narp is greatly enhanced by BDNF. Furthermore, our results show that BDNF directly regulates Narp to mediate glutamatergic transmission and mossy fiber plasticity. Hence, Narp serves as a significant epistatic target of BDNF to regulate synaptic plasticity during periods of dynamic activity.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Brain-Derived Neurotrophic Factor / genetics
Brain-Derived Neurotrophic Factor / metabolism
Brain-Derived Neurotrophic Factor / pharmacology*
C-Reactive Protein / antagonists & inhibitors
C-Reactive Protein / genetics
C-Reactive Protein / metabolism*
Cells, Cultured
Dactinomycin / pharmacology
Down-Regulation / drug effects
Female
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mitogen-Activated Protein Kinases / antagonists & inhibitors
Mitogen-Activated Protein Kinases / metabolism
Nerve Tissue Proteins / antagonists & inhibitors
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Neuronal Plasticity / drug effects
Neurons / cytology
Neurons / drug effects
Neurons / metabolism
Phospholipase C gamma / metabolism
Promoter Regions, Genetic
Protein Kinase Inhibitors / pharmacology
Rats
Rats, Sprague-Dawley
Receptors, AMPA / metabolism
Signal Transduction / drug effects*
Synapses / metabolism
Transcriptional Activation / drug effects

Substances

Brain-Derived Neurotrophic Factor
Nerve Tissue Proteins
Protein Kinase Inhibitors
Receptors, AMPA
neuronal pentraxin
Dactinomycin
C-Reactive Protein
Mitogen-Activated Protein Kinases
Phospholipase C gamma

Abstract

Publication types

MeSH terms

Substances

Grants and funding