Acetylcholinesterase inhibitor ENA-713 protects against ischemia-induced decrease in pre- and postsynaptic cholinergic indices in the gerbil brain following transient ischemia

K. Tanaka, N. Ogawa, K. Mizukawa, M. Asanuma, Yoichi Kondo, S. Nishibayashi, A. Mori

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36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)117-122
Number of pages6
JournalNeurochemical Research
Volume19
Issue number2
DOIs
Publication statusPublished - Feb 1 1994

Keywords

  • Acetylcholinesterase inhibitor
  • ENA-713
  • cholinergic indices
  • transient ischemia

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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