Impairment of spatial learning and memory in ELKL Motif Kinase1 (EMK1/MARK2) knockout mice.
The hyperphosphorylation of tau protein is one of the hallmarks of Alzheimer's disease (AD) and of the associated cognitive decline. EMK1 (MARK2) is a serine/threonine kinase which phosphorylates tau and MAP2. An involvement of this kinase in memory functions is not established. We used a behavioral approach to study the phenotype of EMK1-null mice (EMK1-KO) as a possible model of MAP2/tau altered phophorylation. Compared to wild type mice, EMK1-KO mice did not differ in non-cognitive aspects of behavior, such as locomotion in activity cages, or anxiety in the elevated plus maze. However, they exhibited lower performance in the first stage of acquisition of a hippocampal-dependent spatial learning, as assessed in a radial water maze, although, they acquired the task with repeated training. They were again found to be impaired on re-learning a new platform position. In addition, they exhibited poor long-term retention performance. These data underline the importance on both early memory processes and long-term retrieval, of the dynamic instability of microtubules generated by the phosphorylation of MAPs.
Segu
Louis
L
Laboratoire de Neurosciences Cognitives, CNRS UMR 5106, Université de Bordeaux 1, Avenue des Facultés, 33405 Talence Cedex, France. l.segu@lnc.u-bordeaux1.fr
Pascaud
Arnaud
A
Costet
Pierre
P
Darmon
Michel
M
Buhot
Marie-Christine
MC
D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000235:genetics; D001522:Behavior, Animal; D018797:Cell Cycle Proteins; D007858:Learning / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency*; D013028:Space Perception / Q000502:physiology*; D013997:Time Factors
D018797:Cell Cycle Proteins; C122043:Mark2 protein, mouse; D017346:Protein Serine-Threonine Kinases