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.; Figura, S.; Stoll, M.; Schwartz, S.; Pape, H. C.; Schultze, J. L.; Weinshenker, D.; Heneka, M. T.; Urban, I.

doi:10.1523/JNEUROSCI.4027-13.2014

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

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

MPS-Authors

/persons/resource/persons15217

Martinez, A.
Department of Genes and Behavior, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons15030

Eichele, G.
Department of Genes and Behavior, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons134429

Urban, I.
Department of Genes and Behavior, MPI for biophysical chemistry, Max Planck Society;

External Resource

http://www.jneurosci.org/content/34/26/8845.full.pdf+html
(Publisher version)

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

2048461.pdf
(Publisher version), 4MB

Supplementary Material (public)

2048461-Corr.pdf
(Supplementary material), 25KB

Citation

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.

Cite as: https://hdl.handle.net/11858/00-001M-0000-001A-244F-B

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.