Wnt Signaling in Amygdala-Dependent Learning and Memory

In addition to its role in cellular development and proliferation, there are emerging in vitro data implicating the Wnt/β-catenin pathway in synaptic plasticity. Yet in vivo studies have not examined whether Wnt activity is required for learning and memory. In the amygdala during fear memory formation, we found that many Wnt-signaling genes were dynamically regulated, with an immediate decrease, followed by an eventual normalization during memory consolidation. This rapid decrease in Wnt mRNA was confirmed with individual quantitative PCR and in situ hybridization. We then manipulated Wnt signaling with a specific peptide antagonist (Dkk-1) or agonist (Wnt1) injected stereotaxically into the adult amygdala during fear learning. We found that neither manipulation had an effect on locomotion, anxiety, fear acquisition, or fear expression. However, both Wnt modulators prevented long-term fear memory consolidation without affecting short-term memory. Dkk-1 and Wnt infusions had destabilizing, but opposite, effects on the requisite β-catenin/cadherin dynamic interactions that occur during consolidation. These data suggest that dynamic modulation of Wnt/β-catenin signaling during consolidation is critical for the structural basis of long-term memory formation.Burroughs Wellcome FundNational Institutes of Health (U.S.) (DA019624)National Institutes of Health (U.S.) (P30 NS055077)National Science Foundation (U.S.) (GRFP DGE-0234618)National Science Foundation (U.S.) (Center for Behavioral Neuroscience, Agreement #IBN-9876754)National Institutes of Health (U.S.) (National Primate Research Center Base Grant, #RR-00165)National Institutes of Health (U.S.) (Animal Resource Program

A novel mechanism of nuclear factor-kappaB regulation by adenoviral protein 14.7K

Viruses have evolved many different ways to evade immune attacks. The adenoviral E3 protein 14.7K effectively inhibits antiviral immunity and inflammation. However, the underlying mechanism for this effect is unclear. Here we show that 14.7K is a potent inhibitor of nuclear factor (NF)-kappaB transcriptional activity following Toll-like receptor (TLR) or tumour necrosis factor (TNF) receptor signalling. The inhibition of the NF-kappaB activity occurs downstream of IkappaBalpha degradation and NF-kappaB translocation into the nucleus. Analysis of NF-kappaB DNA binding reveals that 14.7K specifically inhibits p50 homodimer DNA binding and that this inhibition is mediated through the interaction of 14.7K with p50. We propose that 14.7K inhibits NF-kappaB activity through directly blocking p50 binding to DNA and that this is the basis for its anti-inflammatory properties. Our data also indicate a role for p50 homodimer-dependent transcription in inflammation

A novel mechanism of nuclear factor-kappaB regulation by adenoviral protein 14.7K

Viruses have evolved many different ways to evade immune attacks. The adenoviral E3 protein 14.7K effectively inhibits antiviral immunity and inflammation. However, the underlying mechanism for this effect is unclear. Here we show that 14.7K is a potent inhibitor of nuclear factor (NF)-kappaB transcriptional activity following Toll-like receptor (TLR) or tumour necrosis factor (TNF) receptor signalling. The inhibition of the NF-kappaB activity occurs downstream of IkappaBalpha degradation and NF-kappaB translocation into the nucleus. Analysis of NF-kappaB DNA binding reveals that 14.7K specifically inhibits p50 homodimer DNA binding and that this inhibition is mediated through the interaction of 14.7K with p50. We propose that 14.7K inhibits NF-kappaB activity through directly blocking p50 binding to DNA and that this is the basis for its anti-inflammatory properties. Our data also indicate a role for p50 homodimer-dependent transcription in inflammation

Simulation eines MOSFET-Transistors mit dem Gummel-Algorithmus

SIGLETIB Hannover: RO 6083(1) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman