AMPA-ergic regulation of amyloid-β levels in an Alzheimer's disease mouse model

Molecular Neurodegeneration
Jane C HettingerJohn R Cirrito

Abstract

Extracellular aggregation of the amyloid-β (Aβ) peptide into toxic multimers is a key event in Alzheimer's disease (AD) pathogenesis. Aβ aggregation is concentration-dependent, with higher concentrations of Aβ much more likely to form toxic species. The processes that regulate extracellular levels of Aβ therefore stand to directly affect AD pathology onset. Studies from our lab and others have demonstrated that synaptic activity is a critical regulator of Aβ production through both presynaptic and postsynaptic mechanisms. AMPA receptors (AMPA-Rs), as the most abundant ionotropic glutamate receptors, have the potential to greatly impact Aβ levels. In order to study the role of AMPA-Rs in Aβ regulation, we used in vivo microdialysis in an APP/PS1 mouse model to simultaneously deliver AMPA and other treatments while collecting Aβ from the interstitial fluid (ISF). Changes in Aβ production and clearance along with inflammation were assessed using biochemical approaches. IL-6 deficient mice were utilized to test the role of IL-6 signaling in AMPA-R-mediated regulation of Aβ levels. We found that AMPA-R activation decreases in ISF Aβ levels in a dose-dependent manner. Moreover, the effect of AMPA treatment involves three distinct pat...Continue Reading

References

Jan 1, 1992·Progress in Brain Research·L F EngY L Lee
Apr 10, 1992·Science·J A Hardy, G A Higgins
Nov 1, 1993·The European Journal of Neuroscience·B SchöbitzF Holsboer
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·A LomakinG B Benedek
Aug 1, 1997·Progress in Neurobiology·R A Gadient, U H Otten
May 5, 2001·Biomolecular Engineering·J L JankowskyD R Borchelt
Jun 14, 2002·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Eric JüttlerMarkus Schwaninger
Feb 25, 2003·Nature Neuroscience·Melanie Meyer-LuehmannMathias Jucker
Apr 3, 2003·Neuron·Flavio KamenetzRoberto Malinow
Sep 16, 2003·International Journal of Geriatric Psychiatry·Paul T Francis
Dec 5, 2003·Nucleic Acids Research·Xiaowei Wang, Brian Seed
Jun 24, 2004·Neurobiology of Aging·Joanna L JankowskyDavid R Borchelt
Jun 26, 2004·Science·Michael A SuttonErin M Schuman
Aug 27, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Randy L BucknerMark A Mintun
Oct 14, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sylvain LesnéAlain Buisson
Dec 21, 2005·Neuron·John R CirritoDavid M Holtzman
Feb 24, 2006·Proceedings of the National Academy of Sciences of the United States of America·Eric H ChangPatricio T Huerta
Jan 26, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Pascale N LacorWilliam L Klein
Apr 10, 2007·Trends in Neurosciences·Vikram R Rao, Steven Finkbeiner
Apr 19, 2007·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Adam DenesStuart M Allan
May 18, 2007·Annual Review of Cell and Developmental Biology·Jason D Shepherd, Richard L Huganir
Oct 30, 2007·Nature Neuroscience·Uwe-Karsten Hanisch, Helmut Kettenmann
Apr 2, 2008·European Journal of Pharmacology·Elena MarcelloMonica Di Luca
Oct 3, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Deniz AtasoyEge T Kavalali
Oct 10, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Carrie K JonesP Jeffrey Conn
Feb 13, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Randy L BucknerKeith A Johnson
Apr 10, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sarah E HoeyMichael S Perkinton
Aug 28, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ping YanJin-Moo Lee
Oct 15, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Paramita ChakrabartyPritam Das
Dec 29, 2009·Nature Neuroscience·Wei WeiRoberto Malinow
Mar 20, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Soong Ho KimSam Gandy

❮ Previous
Next ❯

Citations

Nov 30, 2019·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Dimitri HefterMartin Korte
Jan 2, 2019·Cellular and Molecular Life Sciences : CMLS·Simona MagiSalvatore Amoroso
May 30, 2020·Molecular Psychiatry·Swagata GhatakStuart A Lipton
Sep 12, 2020·Neurology·John R CirritoYvette I Sheline
Nov 21, 2020·Journal of Alzheimer's Disease : JAD·Oriol BusquetsCarme Auladell
Dec 29, 2020·Frontiers in Cell and Developmental Biology·Mengxi NiuYun-Wu Zhang
Jan 26, 2021·Journal of Alzheimer's Disease : JAD·Masaki NakanoMasaki Nishimura
Aug 28, 2021·International Journal of Molecular Sciences·Emilio Garro-MartínezFuencisla Pilar-Cuéllar

❮ Previous
Next ❯

Datasets Mentioned

BETA
GM6001

Methods Mentioned

BETA
transgenic
ELISA
ELISAs
electrophoresis
PCR

Software Mentioned

Prism
Kodak 1D Image Analysis

Related Concepts

Related Feeds

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.

© 2022 Meta ULC. All rights reserved