title: Definition of a Bidirectional Activity-Dependent Pathway Involving BDNF and Narp.
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.
authors.affiliation: 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.
authors.forename: Abigail
authors.initials: A
authors.lastname: Mariga
authors.affiliation: Unit of Genetics and Biology of Development, Institut Curie, 75005 Paris, France.
authors.forename: Juliane
authors.initials: J
authors.lastname: Glaser
authors.affiliation: Magistère de Génétique Graduate Program, Université Paris Diderot, 75013 Paris, France.
authors.forename: Leo
authors.initials: L
authors.lastname: Mathias
authors.affiliation: Departments of Neuroscience and Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Desheng
authors.initials: D
authors.lastname: Xu
authors.affiliation: Departments of Neuroscience and Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Meifang
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Departments of Neuroscience and Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Worley
authors.affiliation: Department of Psychiatry, New York, University, Langone Medical Center, New York, New YorkNY 10016, USA.
authors.forename: Ipe
authors.initials: I
authors.lastname: Ninan
authors.affiliation: 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.
authors.forename: Moses V
authors.initials: MV
authors.lastname: Chao
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013569:Synapses / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D000099153:Pentraxins
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002097:C-Reactive Protein; D003609:Dactinomycin; D020928:Mitogen-Activated Protein Kinases; D009419:Nerve Tissue Proteins; D051966:Phospholipase C gamma; D047428:Protein Kinase Inhibitors; D018091:Receptors, AMPA; D000099153:Pentraxins