To assess the consequences of locus ceruleus (LC) degeneration and subsequent noradrenaline (NA) deficiency in early Alzheimer's disease (AD), mice overexpressing mutant amyloid precursor protein and presenilin-1 (APP/PS1) were crossed with Ear2(-/-) mice that have a severe loss of LC neurons projecting to the hippocampus and neocortex. Testing spatial memory and hippocampal long-term potentiation revealed an impairment in APP/PS1 Ear2(-/-) mice, whereas APP/PS1 or Ear2(-/-) mice showed only minor changes. These deficits were associated with distinct synaptic changes including reduced expression of the NMDA 2A subunit and increased levels of NMDA receptor 2B in APP/PS1 Ear2(-/-) mice. Acute pharmacological replacement of NA by L-threo-DOPS partially restored phosphorylation of β-CaMKII and spatial memory performance in APP/PS1 Ear2(-/-) mice. These changes were not accompanied by altered APP processing or amyloid β peptide (Aβ) deposition. Thus, early LC degeneration and subsequent NA reduction may contribute to cognitive deficits via CaMKII and NMDA receptor dysfunction independent of Aβ and suggests that NA supplementation could be beneficial in treating AD.
Pubmed ID: 24966384 RIS Download
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Public registry of antibodies with unique identifiers for commercial and non-commercial antibody reagents to give researchers a way to universally identify antibodies used in publications. The registry contains antibody product information organized according to genes, species, reagent types (antibodies, recombinant proteins, ELISA, siRNA, cDNA clones). Data is provided in many formats so that authors of biological papers, text mining tools and funding agencies can quickly and accurately identify the antibody reagents they and their colleagues used. The Antibody Registry allows any user to submit a new antibody or set of antibodies to the registry via a web form, or via a spreadsheet upload.
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