Acetylcholinesterase inhibitor ENA-713 protects against ischemia-induced decrease in pre- and postsynaptic cholinergic indices in the gerbil brain following transient ischemia.
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.
Tanaka
K
K
Department of Neuroscience, Okayama University Medical School, Japan.
Ogawa
N
N
Mizukawa
K
K
Asanuma
M
M
Kondo
Y
Y
Nishibayashi
S
S
Mori
A
A
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002219:Carbamates / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D048448:Phenylcarbamates; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D000068836:Rivastigmine; D013569:Synapses / Q000378:metabolism*
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D011976:Receptors, Muscarinic; D000109:Acetylcholine; D000068836:Rivastigmine