TY - JOUR T1 - Ear2 Deletion Causes Early Memory and Learning Deficits in APP/PS1 Mice JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8845 LP - 8854 DO - 10.1523/JNEUROSCI.4027-13.2014 VL - 34 IS - 26 AU - Markus P. Kummer AU - Thea Hammerschmidt AU - Ana Martinez AU - Dick Terwel AU - Gregor Eichele AU - Anika Witten AU - Stefanie Figura AU - Monika Stoll AU - Stephanie Schwartz AU - Hans-Christian Pape AU - Joachim L. Schultze AU - David Weinshenker AU - Michael T. Heneka Y1 - 2014/06/25 UR - http://www.jneurosci.org/content/34/26/8845.abstract N2 - 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. ER -