pISSN 1226-4512 eISSN 2093-3827


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Original Article

Korean J Physiol Pharmacol 2013; 17(4): 331-338

Published online August 30, 2013 https://doi.org/10.4196/kjpp.2013.17.4.331

Copyright © The Korean Journal of Physiology & Pharmacology.

Neuroprotective Effects of AMP-Activated Protein Kinase on Scopolamine Induced Memory Impairment

Soo-Jeong Kim1,*, Jun-Ho Lee1,*, Hwan-Suck Chung1, Joo-Hyun Song1, Joohun Ha2, and Hyunsu Bae1,3

1College of Korean Medicine, 2School of Medicine, 3Institute of Oriental Medicine, Kyung Hee University, Seoul 130-701, Korea

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, is activated in response to cellular stress when intracellular levels of AMP increase. We investigated the neuroprotective effects of AMPK against scopolamine-induced memory impairment in vivo and glutamate-induced cytotoxicity in vitro. An adenovirus expressing AMPK wild type alpha subunit (WT) or a dominant negative form (DN) was injected into the hippocampus of rats using a stereotaxic apparatus. The AMPK WT-injected rats showed significant reversal of the scopolamine induced cognitive deficit as evaluated by escape latency in the Morris water maze. In addition, they showed enhanced acetylcholinesterase (AChE)-reactive neurons in the hippocampus, implying increased cholinergic activity in response to AMPK. We also studied the cellular mechanism by which AMPK protects against glutamate- induced cell death in primary cultured rat hippocampal neurons. We further demonstrated that AMPK WT-infected cells increased cell viability and reduced Annexin V positive hippocampal neurons. Western blot analysis indicated that AMPK WT-infected cells reduced the expression of Bax and had no effects on Bcl-2, which resulted in a decreased Bax/Bcl-2 ratio. These data suggest that AMPK is a useful cognitive impairment treatment target, and that its beneficial effects are mediated via the protective capacity of hippocampal neurons.

Keywords: Adenovirus, AMPK, Apoptosis, Learning and memory, Scopolamine