Neuronal-glial interactions mediated by interleukin-1 enhance neuronal acetylcholinesterase activity and mRNA expression.
Cholinergic dysfunction in Alzheimer's disease has been attributed to stress-induced increases in acetylcholinesterase (AChE) activity. Interleukin-1 (IL-1) is overexpressed in Alzheimer's disease, and stress-related changes in long-term potentiation, an ACh-related cerebral function, are triggered by interleukin-1. Microglial cultures (N9) synthesized and released IL-1 in response to conditioned media obtained from glutamate-treated primary neuron cultures or PC12 cells. This conditioned media contained elevated levels of secreted beta-amyloid precursor protein (sAPP). Naive PC12 cells cocultured with stimulated N9 cultures showed increased AChE activity and mRNA expression. These effects on AChE expression and activity could be blocked by either preincubating the glutamate-treated PC12 supernatants with anti-sAPP antibodies or preincubating naive PC12 cells with IL-1 receptor antagonist. These findings were confirmed in vivo; IL-1-containing pellets implanted into rat cortex also increased AChE mRNA levels. Neuronal stress in Alzheimer's disease may induce increases in AChE expression and activity through a molecular cascade that is mediated by sAPP-induced microglial activation and consequent overexpression of IL-1.
Li
Y
Y
Donald W. Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Liu
L
L
Kang
J
J
Sheng
J G
JG
Barger
S W
SW
Mrak
R E
RE
Griffin
W S
WS
D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D017628:Microglia / Q000166:cytology*; D009474:Neurons / Q000166:cytology* / Q000201:enzymology; D016716:PC12 Cells; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D016564:Amyloid beta-Protein Precursor; D007375:Interleukin-1; D012333:RNA, Messenger; D018698:Glutamic Acid; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase