He Select Action of Hippocampal Calcium Calmodulin Rotein Kinase Ii in Mediating Exercise-enhanced Ognitive Function

bstract—We found that a single week of exercise enhanced ognitive function on the Morris water maze (MWM), such hat exercise animals were significantly better than sedentary ontrols at learning and recalling the location of the platform. n order to elucidate the role that calcium calmodulin protein inase II (CAMKII) holds in mediating the exercise-induced nhancement in learning and memory, a specific antagonist f CAMKII, KN-62, was used to block CAMKII in the rat hipocampus during a 1-week voluntary exercise period. Followng, a two-trial-per-day MWM was performed for five consective days, succeeded by a probe trial 2 days later. Inhibiting AMKII action during exercise blocked the ability of exercise o enhance memory retention on the MWM; the recall abilities f exercise animals receiving the CAMKII blocker were sigificantly worse than those of both sedentary and exercise ontrols. Conversely, CAMKII may not play a significant role n mediating the effects of exercise on learning acquisition as nhibiting CAMKII failed to block the exercise-induced enancement in learning acquisition. Our results also show that AMKII activation early during MWM learning may be counerproductive to learning acquisition, as exercising animals iven the CAMKII inhibitor performed significantly (P<0.001) etter than exercising control animals and sedentary conrols only on day 2 of the MWM. Inhibiting CAMKII also locked the exercise-induced upregulation of molecules critcal for learning and memory, brain-derived neurotrophic facor (BDNF) and the transcription activator cAMP responselement-binding protein, which is regulated by and downtream to BDNF action. These findings indicate that ippocampal CAMKII may have a refined role in mediating the ffects of exercise on cognition, selectively functioning to egulate memory retention. © 2006 IBRO. Published by lsevier Ltd. All rights reserved.