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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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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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Authors and Affiliations

  1. Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical School, 2-5-1 Shikatacho, 700, Okayama, Japan

    K. Tanaka, N. Ogawa, M. Asanuma, Y. Kondo, S. Nishibayashi & A. Mori

  2. Department of Anatomy, Okayama University Medical School, 2-5-1 Shikatacho, 700, Okayama, Japan

    K. Mizukawa

  3. Third Department of Internal Medicine, Okayama University Medical School, 2-5-1 Shikatacho, 700, Okayama, Japan

    Y. Kondo

Authors
  1. K. Tanaka
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  2. N. Ogawa
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  4. M. Asanuma
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  5. Y. Kondo
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  6. S. Nishibayashi
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Tanaka, K., Ogawa, N., Mizukawa, K. et al. Acetylcholinesterase inhibitor ENA-713 protects against ischemia-induced decrease in pre- and postsynaptic cholinergic indices in the gerbil brain following transient ischemia. Neurochem Res 19, 117–122 (1994). https://doi.org/10.1007/BF00966804

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