The Journal of Neuroscience, January 1, 2000, 20(1):149-155
Neuronal-Glial Interactions Mediated by Interleukin-1 Enhance
Neuronal Acetylcholinesterase Activity and mRNA Expression
Yuekui
Li1,
Ling
Liu1,
Jinsong
Kang1, 9,
Jin G.
Sheng1,
Steven W.
Barger1, 2, 6,
Robert E.
Mrak2, 3, 8, and
W. Sue T.
Griffin1, 2, 4, 5, 6, 7
1 Donald W. Reynolds Department of Geriatrics and the
Departments of 2 Anatomy, 3 Pathology,
4 Medicine, and 5 Psychiatry, University of
Arkansas for Medical Sciences, Little Rock, Arkansas 72205, 6 the Geriatric Research, Education, Clinical Center,
7 Mental Illness Research Education and Clinical Center,
and 8 Pathology Service, McClellan Memorial Veterans
Affairs Medical Center, Little Rock, Arkansas 72205, and
9 Department of Pathophysiology, Norman Bethune University
of Medical Sciences, Changchun 130021, People's Republic of
China
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
-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.
Key words:
acetylcholinesterase; Alzheimer's disease; -amyloid
precursor protein; choline acetyltransferase; cholinergic systems; interleukin-1; neuronal cultures; neuronal stress; PC12 cells
Copyright © 2000 Society for Neuroscience 0270-6474/0/201149-07$05.00/0
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