Protection against ischemic injury in primary cultured mouse astrocytes by bis(7)-tacrine, a novel acetylcholinesterase inhibitor [corrected].
The effects of bis(7)-tacrine, a novel acetylcholinesterase inhibitor, on ischemia-induced cell death and apoptosis were investigated in primary cerebral cortical astrocytes of mice. Following a 6 h in vitro ischemic incubation of the cultures, a marked decrease in the percentage of viable cells was observed by lactate dehydrogenase (LDH) release assay. Furthermore, using bisbenzimide staining, we determined that approximately 65% of the cells underwent apoptosis. Treatment with bis(7)-tacrine (1-10 nM) during ischemic incubation effectively inhibited the ischemia-induced apoptosis, as demonstrated by morphological and biochemical tests. Our results demonstrated that bis(7)-tacrine could protect astrocytes against ischemia-induced cell injury, indicating that the drug might be beneficial for the treatment of vascular dementia, in addition to Alzheimer's disease.
Wu
D C
DC
Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Xiao
X Q
XQ
Ng
A K
AK
Chen
P M
PM
Chung
W
W
Lee
N T
NT
Carlier
P R
PR
Pang
Y P
YP
Yu
A C
AC
Han
Y F
YF
Wu
D
D
Xiao
X
X
Pang
Y
Y
Han
Y
Y
D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000201:enzymology / Q000473:pathology*; D002545:Brain Ischemia / Q000201:enzymology / Q000473:pathology* / Q000517:prevention & control*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013619:Tacrine / Q000031:analogs & derivatives* / Q000627:therapeutic use*
C122128:1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine; D002800:Cholinesterase Inhibitors; D013619:Tacrine