Acetylcholinesterase induces the expression of the beta-amyloid precursor protein in glia and activates glial cells in culture.
Acetylcholinesterase (AChE) activities in CNS physiopathology are increasingly diverse and range from neuritogenesis, through synaptogenesis, to enhancement of amyloid fiber assembly. In Alzheimer's disease, senile plaques and neurodegeneration specially affect regions enriched for cholinergic synapses. In this study we show an effect of AChE that could contribute to the increased deposition of Abeta in certain regions. Affinity-purified AChE induced the expression of amyloid-beta-precursor protein (beta-APP) in glial cells in a concentration-dependent manner up to 5 nM. In glia, AChE also increased inducible nitric oxide synthase (iNOS) assessed by immunocytochemistry and decreased reductive metabolism as evidence of cell activation. AChE could increase the expression of beta-APP in astrocytes and microglia as result of the activation of glial cells. As a whole, we found that AChE has additional effects that could result in an increased synthesis of Abeta, both by increasing beta-APP expression of astrocytes and by further activating glial cells.
von Bernhardi
Rommy
R
Departamento de Neurología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. rvonb@med.puc.cl
Ramírez
Gigliola
G
De Ferrari
Giancarlo V
GV
Inestrosa
Nibaldo C
NC
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D000544:Alzheimer Disease / Q000201:enzymology* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology; D001921:Brain / Q000201:enzymology* / Q000503:physiopathology; D002478:Cells, Cultured; D002799:Cholinergic Fibers / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005911:Gliosis / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D017628:Microglia / Q000187:drug effects / Q000201:enzymology; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000110:Acetylcholinesterase; D000109:Acetylcholine