English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Effects of rising amyloidβ levels on hippocampal synaptic transmission, microglial response and cognition in APPSwe/PSEN1M146V transgenic mice

Medawar, E., Benway, T. A., Liu, W., Hanan, T. A., Haslehurst, P., James, O. T., et al. (2019). Effects of rising amyloidβ levels on hippocampal synaptic transmission, microglial response and cognition in APPSwe/PSEN1M146V transgenic mice. EBioMedicine, 39, 422-435. doi:10.1016/j.ebiom.2018.12.006.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0002-BB63-C Version Permalink: http://hdl.handle.net/21.11116/0000-0003-9093-3
Genre: Journal Article

Files

show Files
hide Files
:
Medawar_2019.pdf (Publisher version), 3MB
Name:
Medawar_2019.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Medawar, Evelyn1, Author              
Benway, Tiffanie A.1, Author
Liu, Wenfei 1, Author
Hanan, Taylor A. 1, Author
Haslehurst, Peter 1, Author
James, Owain T. 1, Author
Yap, Kenrick 1, Author
Muessig, Laurenz 1, Author
Moroni, Fabia 1, Author
Nahaboo Solim, Muzammil A. 1, 2, Author
Baidildinova, Gaukhar 1, 3, Author
Wang, Rui 1, Author
Richardson, Jill C.1, Author
Cacucc, Francesca1, Author
Salih, Dervis A. 1, Author
Cummings, Damian M. 1, Author
Edwards, Frances A. 1, Author
Affiliations:
1Department of Neuroscience, Physiology and Pharmacology, University College London, United Kingdom, ou_persistent22              
2Institute of Cellular Medicine, Newcastle University, United Kingdom, ou_persistent22              
3Department of Science and Innovations, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan, ou_persistent22              

Content

show
hide
Free keywords: Alzheimer's disease; Dementia; Mouse model; Synaptic transmission; Microglia; Plaque; Neurodegeneration
 Abstract: Background Progression of Alzheimer's disease is thought initially to depend on rising amyloidβ and its synaptic interactions. Transgenic mice (TASTPM; APPSwe/PSEN1M146V) show altered synaptic transmission, compatible with increased physiological function of amyloidβ, before plaques are detected. Recently, the importance of microglia has become apparent in the human disease. Similarly, TASTPM show a close association of plaque load with upregulated microglial genes. Methods CA1 synaptic transmission and plasticity were investigated using in vitro electrophysiology. Microglial relationship to plaques was examined with immunohistochemistry. Behaviour was assessed with a forced-alternation T-maze, open field, light/dark box and elevated plus maze. Findings The most striking finding is the increase in microglial numbers in TASTPM, which, like synaptic changes, begins before plaques are detected. Further increases and a reactive phenotype occur later, concurrent with development of larger plaques. Long-term potentiation is initially enhanced at pre-plaque stages but decrements with the initial appearance of plaques. Finally, despite altered plasticity, TASTPM have little cognitive deficit, even with a heavy plaque load, although they show altered non-cognitive behaviours. Interpretation The pre-plaque synaptic changes and microglial proliferation are presumably related to low, non-toxic amyloidβ levels in the general neuropil and not directly associated with plaques. However, as plaques grow, microglia proliferate further, clustering around plaques and becoming phagocytic. Like in humans, even when plaque load is heavy, without development of neurofibrillary tangles and neurodegeneration, these alterations do not result in cognitive deficits. Behaviours are seen that could be consistent with pre-diagnosis changes in the human condition.

Details

show
hide
Language(s): eng - English
 Dates: 2018-12-032018-09-202018-12-052018-12-132019-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.ebiom.2018.12.006
PMID: 30555043
Other: Epub ahead of print
PII: S2352-3964(18)30577-2
 Degree: -

Event

show

Legal Case

show

Project information

show hide
Project name : -
Grant ID : -
Funding program : BBSRC Case Studentship
Funding organization : GlaxoSmithKline
Project name : -
Grant ID : -
Funding program : UCL International Studentship
Funding organization : University College London
Project name : -
Grant ID : MR/J011851/1
Funding program : -
Funding organization : Medical Research Council (MRC)
Project name : -
Grant ID : BB/R009872/1
Funding program : -
Funding organization : Biotechnology and Biological Sciences Research Council (BBSRC)

Source 1

show
hide
Title: EBioMedicine
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Amsterdam : Elsevier
Pages: - Volume / Issue: 39 Sequence Number: - Start / End Page: 422 - 435 Identifier: ISSN: 2352-3964
CoNE: https://pure.mpg.de/cone/journals/resource/2352-3964