GABA(A) receptor-mediated acceleration of aging-associated memory decline in APP/PS1 mice and its pharmacological treatment by picrotoxin.

PloS One
Yuji YoshiikeAkihiko Takashima

Abstract

Advanced age and mutations in the genes encoding amyloid precursor protein (APP) and presenilin (PS1) are two serious risk factors for Alzheimer's disease (AD). Finding common pathogenic changes originating from these risks may lead to a new therapeutic strategy. We observed a decline in memory performance and reduction in hippocampal long-term potentiation (LTP) in both mature adult (9-15 months) transgenic APP/PS1 mice and old (19-25 months) non-transgenic (nonTg) mice. By contrast, in the presence of bicuculline, a GABA(A) receptor antagonist, LTP in adult APP/PS1 mice and old nonTg mice was larger than that in adult nonTg mice. The increased LTP levels in bicuculline-treated slices suggested that GABA(A) receptor-mediated inhibition in adult APP/PS1 and old nonTg mice was upregulated. Assuming that enhanced inhibition of LTP mediates memory decline in APP/PS1 mice, we rescued memory deficits in adult APP/PS1 mice by treating them with another GABA(A) receptor antagonist, picrotoxin (PTX), at a non-epileptic dose for 10 days. Among the saline vehicle-treated groups, substantially higher levels of synaptic proteins such as GABA(A) receptor alpha1 subunit, PSD95, and NR2B were observed in APP/PS1 mice than in nonTg control mic...Continue Reading

References

Dec 15, 1994·Annals of the New York Academy of Sciences·Z S Khachaturian
Apr 1, 1994·The International Journal of Neuroscience·I Daum, H Ackermann
Jan 7, 1993·Nature·T V Bliss, G L Collingridge
Jan 15, 2000·Science·J L McGaugh
Sep 21, 2000·Behavioural Brain Research·M M van Gaalen, T Steckler
Aug 13, 2002·Current Topics in Medicinal Chemistry·Georges Chapouthier, Patrice Venault
Nov 5, 2002·Nature Reviews. Neuroscience·Frank M LaFerla
Apr 5, 2003·Journal of Neurochemistry·José VelaDiego Ruano
May 13, 2003·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·C A Barnes
Aug 22, 2003·Proceedings of the National Academy of Sciences of the United States of America·Rusiko BourtchouladzeTim Tully
Nov 25, 2003·Current Opinion in Neurobiology·Juan Burrone, Venkatesh N Murthy
Dec 25, 2003·Journal of Neuropathology and Experimental Neurology·Joanna L JankowskyDavid R Borchelt
Sep 17, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alexander M KleschevnikovWilliam C Mobley
May 27, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Joanna L JankowskyAlena V Savonenko
Jul 19, 2005·Nature Neuroscience·Eric M SnyderPaul Greengard
Nov 16, 2005·Nature Neuroscience·Hey-Kyoung LeeAlfredo Kirkwood
Dec 2, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·F RoselliO F X Almeida
Jan 3, 2006·Neurobiology of Aging·Myriel NyffelerIrene Knuesel
Feb 10, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yun Ha JeongYoo-Hun Suh
Mar 17, 2006·Nature·Sylvain LesnéKaren H Ashe
May 12, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Grace E StutzmannIan Parker
Oct 20, 2006·Nature·Jorge J PalopLennart Mucke
Jan 26, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Pascale N LacorWilliam L Klein
Feb 27, 2007·Nature Neuroscience·Fabian FernandezCraig C Garner
Mar 16, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ganesh M ShankarBernardo L Sabatini
Jul 24, 2007·Neuropharmacology·Bo-Shiun Chen, Katherine W Roche
Aug 24, 2007·Journal of Neurochemistry·Robert A RissmanDavid M Armstrong
Aug 8, 2012·Proceedings of the National Academy of Sciences of the United States of America·Pascal E SanchezLennart Mucke

❮ Previous
Next ❯

Citations

Jul 31, 2013·Neuromolecular Medicine·Francesco MoriDiego Centonze
Feb 11, 2009·Archives of Neurology·Jorge J Palop, Lennart Mucke
Aug 24, 2012·Molecular Neurobiology·Robert NisticòGraham Collingridge
Feb 13, 2016·Neurochemical Research·Xiaona WangPeng Sun
Jan 9, 2013·Behavioural Brain Research·Sherry A FergusonLarry C Schmued
Aug 23, 2012·Pharmacology, Biochemistry, and Behavior·Katia BoumgharCatherine Armengaud
Jul 10, 2010·Neurobiology of Disease·Raphaël PoirierFriedrich Metzger
Aug 24, 2012·Annals of Neurology·Ju ShiKatrin Andreasson
Jan 31, 2016·Journal of Neurochemistry·M Dolores MuñozAmelia Sánchez-Capelo
Jun 16, 2010·Neuron·Karen H Ashe, Kathleen R Zahs
Dec 3, 2014·Nanomedicine : Nanotechnology, Biology, and Medicine·Lara Ordóñez-GutiérrezFrancisco Wandosell
May 4, 2017·Journal of Neuroscience Research·Crystal AcostaChristopher M Anderson
Dec 23, 2009·Bulletin of Experimental Biology and Medicine·P S BabichN S Sapronov
Nov 7, 2018·International Neurourology Journal·Syed M Q Hussaini, Mi Hyeon Jang
Oct 10, 2015·Oncotarget·Hyung-Mun YunJin Tae Hong
Jan 23, 2020·International Journal of Molecular Sciences·Mª Dolores MuñozAmelia Sánchez-Capelo

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic

Software Mentioned

GraphPad
Mathworks
PRISM4
NIH Image
Matlab

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.

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.