title: Neuronal pentraxin 1 negatively regulates excitatory synapse density and synaptic plasticity.
abstract: In mature neurons, the number of synapses is determined by a neuronal activity-dependent dynamic equilibrium between positive and negative regulatory factors. We hypothesized that neuronal pentraxin (NP1), a proapoptotic protein induced by low neuronal activity, could be a negative regulator of synapse density because it is found in dystrophic neurites in Alzheimer's disease-affected brains. Here, we report that knockdown of NP1 increases the number of excitatory synapses and neuronal excitability in cultured rat cortical neurons and enhances excitatory drive and long-term potentiation in the hippocampus of behaving mice. Moreover, we found that NP1 regulates the surface expression of the Kv7.2 subunit of the Kv7 family of potassium channels that control neuronal excitability. Furthermore, pharmacological activation of Kv7 channels prevents, whereas inhibition mimics, the increase in synaptic proteins evoked by the knockdown of NP1. These results indicate that NP1 negatively regulates excitatory synapse number by modulating neuronal excitability and show that NP1 restricts excitatory synaptic plasticity.
authors: Neurobiology Unit, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), 08036 Barcelona, Spain, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors: Joana
authors: http://orcid.org/0000-0003-3590-1784
authors: J
authors: Figueiro-Silva
authors: División de Neurociencias, Universidad Pablo de Olavide, 41013 Sevilla, Spain.
authors: Agnès
authors: A
authors: Gruart
authors: Neurobiology Unit, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), 08036 Barcelona, Spain, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors: Kevin Bernard
authors: KB
authors: Clayton
authors: Neurobiology Unit, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), 08036 Barcelona, Spain, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors: Petar
authors: P
authors: Podlesniy
authors: Neurobiology Unit, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), 08036 Barcelona, Spain, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
authors: Maria Alba
authors: http://orcid.org/0000-0002-8816-1524
authors: MA
authors: Abad
authors: Laboratory of Neurophysiology, School of Medicine, University of Barcelona, 08036 Barcelona, Spain, and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.
authors: Xavier
authors: X
authors: Gasull
authors: División de Neurociencias, Universidad Pablo de Olavide, 41013 Sevilla, Spain.
authors: José María
authors: JM
authors: Delgado-García
authors: Neurobiology Unit, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), 08036 Barcelona, Spain, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain ramon.trullas@iibb.csic.es.
authors: Ramon
authors: R
authors: Trullas
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D014851:Wakefulness / Q000187:drug effects; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D000099153:Pentraxins
keywords: Kv7.2 potassium channels; excitatory synapses; long-term potentiation