Acetylcholinesterase inhibitor ENA-713 protects against ischemia-induced decrease in pre- and postsynaptic cholinergic indices in the gerbil brain following transient ischemia |
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| Authors: | K Tanaka N Ogawa K Mizukawa M Asanuma Y Kondo S Nishibayashi A Mori |
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| Institution: | (1) Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical School, 2-5-1 Shikatacho, 700 Okayama, Japan;(2) Department of Anatomy, Okayama University Medical School, 2-5-1 Shikatacho, 700 Okayama, Japan;(3) Third Department of Internal Medicine, Okayama University Medical School, 2-5-1 Shikatacho, 700 Okayama, Japan |
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| Abstract: | The effects of pre-treatment with ENA-713, an acetylcholinesterase (AChE) inhibitor, on changes in pre- and postsynaptic cholinergic indices in gerbil brain following transient ischemia were studied at 4 and 14 days after recirculation. In the ischemic group, hippocampal acetylcholine (ACh) level was significantly reduced (to 23% of sham-operated controls) at 4 days post-ischemia, but this reduction was completely prevented by ENA-713 treatment. Choline acetyltransferase (ChAT) and cholinesterase (ChE) activities were not significantly changed at 4 and 14 days post-ischemia. Although the maximum number (Bmax) of muscarinic ACh receptor (mACh-R) binding in the hippocampus was decreased (to 44%) without any change in affinity at 14 days post-ischemia, this decrease was also inhibited by ENA-713 treatment. In addition, histological experiment indicated that ENA-713 inhibited ischemia-induced pyramidal cell loss in the hippocampal CA1 regions. Thus, these findings suggest that ENA-713 has protective, neurotrophic and therapeutic effects on cerebrovascular type dementia due to cerebral ischemia. |
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| Keywords: | Acetylcholinesterase inhibitor ENA-713 cholinergic indices transient ischemia |
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