English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  IκB Kinase/Nuclear Factor κB-Dependent Insulin-Like Growth Factor 2 (Igf2) Expression Regulates Synapse Formation and Spine Maturation via Igf2 Receptor Signaling

Schmeisser, M. J., Baumann, B., Johannsen, S., Vindedal, G. F., Jensen, V., Hvalby, Ø. C., et al. (2012). IκB Kinase/Nuclear Factor κB-Dependent Insulin-Like Growth Factor 2 (Igf2) Expression Regulates Synapse Formation and Spine Maturation via Igf2 Receptor Signaling. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience, 32(16), 5688-5703. doi:10.1523/JNEUROSCI.0111-12.2012.

Item is

Basic

show hide
Genre: Journal Article
Alternative Title : IκB Kinase/Nuclear Factor κB-Dependent Insulin-Like Growth Factor 2 (Igf2) Expression Regulates Synapse Formation and Spine Maturation via Igf2 Receptor Signaling

Files

show Files
hide Files
:
JNeurosci_32_2012_5688.pdf (Any fulltext), 4MB
 
File Permalink:
-
Name:
JNeurosci_32_2012_5688.pdf
Description:
-
OA-Status:
Visibility:
Restricted (Max Planck Institute for Medical Research, MHMF; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Description:
-
OA-Status:

Creators

show
hide
 Creators:
Schmeisser, Michael J., Author
Baumann, Bernd, Author
Johannsen, Svenja, Author
Vindedal, Gry F., Author
Jensen, Vidar, Author
Hvalby, Øivind C., Author
Sprengel, Rolf1, Author           
Seither, Jochen, Author
Maqbool, Ayesha, Author
Magnutzki, Alexander, Author
Lattke, Michael, Author
Oswald, Franz, Author
Boeckers, Tobias M., Author
Wirth, Thomas, Author
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              

Content

show
hide
Free keywords: -
 Abstract: Alterations of learning and memory in mice with deregulated neuron−specific nuclear factor κB (NF−κB) activity support the idea that plastic changes of synaptic contacts may depend at least in part on IκB kinase (IKK)/NF−κB−related synapse−to−nucleus signaling. There is, however, little information on the molecular requirements and mechanisms regulating this IKK/NF−κB−dependent synapse development and remodeling. Here, we report that the NF−κB inducing IKK kinase complex is localized at the postsynaptic density (PSD) and activated under basal conditions in the adult mouse brain. Using different models of conditional genetic inactivation of IKK2 function in mouse principal neurons, we show that IKK/NF−κB signaling is critically involved in synapse formation and spine maturation in the adult brain. IKK/NF−κB blockade in the forebrain of mutant animals is associated with reduced levels of mature spines and postsynaptic proteins PSD95, SAP97, GluA1, AMPAR−mediated basal synaptic transmission and a spatial learning impairment. Synaptic deficits can be restored in adult animals within 1 week by IKK/NF−κB reactivation, indicating a highly dynamic IKK/NF−κB−dependent regulation process. We further identified the insulin−like growth factor 2 gene (Igf2) as a novel IKK/NF−κB target. Exogenous Igf2 was able to restore synapse density and promoted spine maturation in IKK/NF−κB signaling−deficient neurons within 24 h. This process depends on Igf2/Igf2R−mediated MEK/ERK activation. Our findings illustrate a fundamental role of IKK/NF−κB−Igf2−Igf2R signaling in synapse formation and maturation in adult mice, thus providing an intriguing link between the molecular actions of IKK/NF−κB in neurons and the memory enhancement factor Igf2

Details

show
hide
Language(s): eng - English
 Dates: 2012-01-092012-03-052012-04-18
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
  Other : J. Neurosci.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Baltimore, MD : The Society
Pages: - Volume / Issue: 32 (16) Sequence Number: - Start / End Page: 5688 - 5703 Identifier: ISSN: 0270-6474
CoNE: https://pure.mpg.de/cone/journals/resource/954925502187_1