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  Ear2 deletion causes early memory and learning deficits in APP/PS1 mice.

Kummer, M. P., Hammerschmidt, T., Martinez, A., Terwel, D., Eichele, G., Witten, A., et al. (2014). Ear2 deletion causes early memory and learning deficits in APP/PS1 mice. Journal of Neuroscience, 34(26), 8845-8854. doi:10.1523/JNEUROSCI.4027-13.2014.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-001A-244F-B Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-1CCF-0
Genre: Journal Article

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 Creators:
Kummer, M. P., Author
Hammerschmidt, T., Author
Martinez, A.1, Author              
Terwel, D., Author
Eichele, G.1, Author              
Witten, A., Author
Figura, S., Author
Stoll, M., Author
Schwartz, S., Author
Pape, H. C., Author
Schultze, J. L., Author
Weinshenker, D., Author
Heneka, M. T., Author
Urban, I.1, Author              
Affiliations:
1Department of Genes and Behavior, MPI for biophysical chemistry, Max Planck Society, ou_persistent34              

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Free keywords: Alzheimer; locus ceruleus; memory; neurodegeneration; noradrenaline
 Abstract: 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 beta-CaMKII and spatial memory performance in APP/PS1 Ear2(-/-) mice. These changes were not accompanied by altered APP processing or amyloid beta peptide (A beta) deposition. Thus, early LC degeneration and subsequent NA reduction may contribute to cognitive deficits via CaMKII and NMDA receptor dysfunction independent of A beta and suggests that NA supplementation could be beneficial in treating AD.

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Language(s): eng - English
 Dates: 2014-06-25
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1523/JNEUROSCI.4027-13.2014
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Title: Journal of Neuroscience
Source Genre: Journal
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Pages: - Volume / Issue: 34 (26) Sequence Number: - Start / End Page: 8845 - 8854 Identifier: -