Intraneuronally injected amyloid β inhibits long-term potentiation in rat hippocampal slices

Journal of Neurophysiology
Izumi NomuraNobuo Kato

Abstract

Extracellular accumulation of amyloid beta (Aβ) is a hallmark of Alzheimer's disease (AD). It has been reported that extracellular perfusion of Aβ inhibits long-term potentiation (LTP), which is strongly related to memory in animal models. However, it has recently been proposed that intracellular Aβ may be the first pathological change to occur in AD. Here, we have investigated the effect on LTP of intracellular injection of Aβ (Aβ(1-40), Aβ(1-42)) into hippocampal pyramidal cells using patch-clamp technique. We found that injection of 1 nM Aβ(1-42) completely blocked LTP, and extracellular perfusion of a p38 MAPK inhibitor or a metabotropic glutamate receptor blocker reversed these blocking effects on LTP. Furthermore, we have examined the effects of different concentrations of Aβ(1-40) and Aβ(1-42) on LTP and showed that Aβ(1-40) required a 1,000-fold higher concentration to attenuate LTP than 1 nM Aβ(1-42). These results indicate that LTP is impaired by Aβ injected into genetically wild-type neurons in the sliced hippocampus, suggesting an acute action of intracellular Aβ on the intracellular LTP-inducing machinery.

References

Nov 11, 1999·European Journal of Pharmacology·A ItohT Nabeshima
Jan 7, 2000·The American Journal of Pathology·G K GourasN R Relkin
Aug 3, 2001·Nature Reviews. Neuroscience·D H SmallJ C Bornstein
Jan 31, 2002·Journal of Molecular Neuroscience : MN·C Glabe
Feb 28, 2002·The Journal of Biological Chemistry·Pascal Kienlen-CampardJean-Noël Octave
Apr 3, 2003·Neuron·Flavio KamenetzRoberto Malinow
May 19, 2004·The European Journal of Neuroscience·Igor KlyubinMichael J Rowan
Jun 25, 2005·Current Alzheimer Research·Bertrand P TsengFrank M LaFerla
Jul 19, 2005·Neurobiology of Aging·Gunnar K GourasReisuke H Takahashi
Jul 19, 2005·Nature Neuroscience·Eric M SnyderPaul Greengard
Jul 22, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Daniela PuzzoOttavio Arancio
Dec 6, 2005·The European Journal of Neuroscience·Qinwen WangRoger Anwyl
Mar 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·J Steven JacobsenFloyd E Bloom
Oct 24, 2006·Neuroscience and Biobehavioral Reviews·L Giménez-LlortA Fernández-Teruel
Jun 7, 2007·Nature Reviews. Neuroscience·Frank M LaFerlaSalvatore Oddo
Sep 7, 2007·The International Journal of Biochemistry & Cell Biology·Peter J CrouchColin L Masters
Sep 15, 2007·The Journal of Biological Chemistry·Matthew TownsendDennis J Selkoe
Sep 25, 2007·Progress in Neurobiology·Meng LiYan Zhang
Mar 28, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nicola OrigliaLuciano Domenici
Aug 11, 2010·EMBO Molecular Medicine·Iryna Benilova, Bart De Strooper
Apr 15, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tao MaEric Klann
May 20, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Andrew E BarryMichael J Rowan
May 27, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Matthew J WintonVirginia M-Y Lee
Aug 5, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kenji YamamotoNobuo Kato
Nov 25, 2011·Journal of Alzheimer's Disease : JAD·Oliver WirthsThomas A Bayer

❮ Previous
Next ❯

Citations

Apr 22, 2014·Neurobiology of Aging·Katja S KrokerCornelia Dorner-Ciossek
Jan 7, 2014·Molecular Neurobiology·David A Hottman, Ling Li
Jun 27, 2015·Pharmaceutical Research·Xiaoyao ZhengXinguo Jiang
Dec 17, 2014·Frontiers in Behavioral Neuroscience·Wenwen BaiXin Tian
Aug 3, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jong Kil Lee, Nam-Jung Kim

❮ Previous
Next ❯

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.