TY - JOUR
T1 - Acetylcholinesterase induces the expression of the β-amyloid precursor protein in glia and activates glial cells in culture
AU - Von Bernhardi, Rommy
AU - Ramírez, Gigliola
AU - De Ferrari, Giancarlo V.
AU - Inestrosa, Nibaldo C.
N1 - Funding Information:
Thanks are due to Dr. Jaime Alvarez for a critical reading of the manuscript, Dr. Heinz Döbeli from Hoffmann-La Roche, Switzerland, for the Aβ peptides and the BAP-1 antibody, Dr. Alejandro Roth for his help with the images, and to Eliseo Campos (M.Sc), for his help with the purification of AChE. This work was supported by FONDECYT 1971132 and 1010146 and MED 006-2000 from Universidad de los Andes to R.v.B, FONDAP 13890001 and Millennium Institute for Fundamental and Applied Biology (MIFAB) P99-007-F.
PY - 2003/12
Y1 - 2003/12
N2 - 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 Aβ in certain regions. Affinity-purified AChE induced the expression of amyloid-β-precursor protein (β-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 β-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 Aβ, both by increasing β-APP expression of astrocytes and by further activating glial cells.
AB - 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 Aβ in certain regions. Affinity-purified AChE induced the expression of amyloid-β-precursor protein (β-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 β-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 Aβ, both by increasing β-APP expression of astrocytes and by further activating glial cells.
KW - AChE inhibitors
KW - Acetylcholinesterase
KW - Alzheimer's disease
KW - Glia
KW - iNOS
KW - β-APP
UR - http://www.scopus.com/inward/record.url?scp=0347479362&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2003.08.014
DO - 10.1016/j.nbd.2003.08.014
M3 - Article
C2 - 14678761
AN - SCOPUS:0347479362
VL - 14
SP - 447
EP - 457
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
IS - 3
ER -