Skip to main content
main-content

01.12.2014 | Research article | Ausgabe 1/2014 Open Access

Molecular Neurodegeneration 1/2014

Temporal gene profiling of the 5XFAD transgenic mouse model highlights the importance of microglial activation in Alzheimer’s disease

Zeitschrift:
Molecular Neurodegeneration > Ausgabe 1/2014
Autoren:
Véréna Landel, Kévin Baranger, Isabelle Virard, Béatrice Loriod, Michel Khrestchatisky, Santiago Rivera, Philippe Benech, François Féron
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1750-1326-9-33) contains supplementary material, which is available to authorized users.
Philippe Benech and François Féron contributed equally to this work.

Competing interests

The authors declare that they have no competing interest.

Authors’ contributions

VL isolated the RNA, helped perform the microarray assay, analyzed the results and wrote the manuscript. KB bred and genotyped the mice, and carried out the qPCR analysis. BL performed the microarray assay. IV and SR participated in interpreting the data and writing the manuscript. PB analyzed the microarray data and wrote the manuscript. FF designed and coordinated the study, and helped to draft the manuscript. All authors read and approved the final manuscript.

Abstract

Background

The 5XFAD early onset mouse model of Alzheimer’s disease (AD) is gaining momentum. Behavioral, electrophysiological and anatomical studies have identified age-dependent alterations that can be reminiscent of human AD. However, transcriptional changes during disease progression have not yet been investigated. To this end, we carried out a transcriptomic analysis on RNAs from the neocortex and the hippocampus of 5XFAD female mice at the ages of one, four, six and nine months (M1, M4, M6, M9).

Results

Our results show a clear shift in gene expression patterns between M1 and M4. At M1, 5XFAD animals exhibit region-specific variations in gene expression patterns whereas M4 to M9 mice share a larger proportion of differentially expressed genes (DEGs) that are common to both regions. Analysis of DEGs from M4 to M9 underlines the predominance of inflammatory and immune processes in this AD mouse model. The rise in inflammation, sustained by the overexpression of genes from the complement and integrin families, is accompanied by an increased expression of transcripts involved in the NADPH oxidase complex, phagocytic processes and IFN-γ related pathways.

Conclusions

Overall, our data suggest that, from M4 to M9, sustained microglial activation becomes the predominant feature and point out that both detrimental and neuroprotective mechanisms appear to be at play in this model. Furthermore, our study identifies a number of genes already known to be altered in human AD, thus confirming the use of the 5XFAD strain as a valid model for understanding AD pathogenesis and for screening potential therapeutic molecules.
Zusatzmaterial
Additional file 1: Table S1: Lists of genes and associated fold changes commonly dysregulated at M1, M4, M6 and M9 in (A) cortex and (B) hippocampus. (PDF 84 KB)
13024_2014_545_MOESM1_ESM.pdf
Additional file 2: Table S2: Common DEGs in cortex and hippocampus at M4, M6 and M9. (PDF 199 KB)
13024_2014_545_MOESM2_ESM.pdf
Authors’ original file for figure 1
13024_2014_545_MOESM3_ESM.tif
Authors’ original file for figure 2
13024_2014_545_MOESM4_ESM.tif
Authors’ original file for figure 3
13024_2014_545_MOESM5_ESM.tif
Authors’ original file for figure 4
13024_2014_545_MOESM6_ESM.tif
Authors’ original file for figure 5
13024_2014_545_MOESM7_ESM.tif
Authors’ original file for figure 6
13024_2014_545_MOESM8_ESM.tif
Authors’ original file for figure 7
13024_2014_545_MOESM9_ESM.tif
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2014

Molecular Neurodegeneration 1/2014 Zur Ausgabe


 

Neu in den Fachgebieten Neurologie und Psychiatrie

Meistgelesene Bücher in der Neurologie & Psychiatrie

  • 2016 | Buch

    Neurologie

    Das Lehrbuch vermittelt Ihnen das gesamte Neurologie-Prüfungswissen für Ihr Medizinstudium und bereitet auch junge Assistenzärzte durch detailliertes Fachwissen optimal auf die Praxis vor. Die komplett überarbeitete Auflage enthält sechs neue, interdisziplinäre Kapitel.

    Herausgeber:
    Werner Hacke
  • 2016 | Buch

    Komplikationen in der Neurologie

    Das Buch schildert Ereignisse im Rahmen der Neuromedizin, die während der Diagnostik und Therapie neurologischer Erkrankungen und Symptome auftreten können. Die Fallbeispiele sensibilisieren Sie für mögliche Risikofaktoren, um das Auftreten solcher Komplikationen zu vermeiden.

    Herausgeber:
    Frank Block
  • 2017 | Buch

    Facharztwissen Psychiatrie, Psychosomatik und Psychotherapie

    Leitsymptome, Untersuchungsmethoden, Krankheitsbilder, Notfälle & Co. – mit der Neuauflage des "Facharztwissens" sind Sie auf die Facharztprüfung in Psychiatrie und Psychotherapie optimal vorbereitet. In dieser 2. Auflage sind die Kapitel zu psychosomatischen Störungen deutlich ausgebaut.

    Herausgeber:
    Prof. Dr. Dr. Frank Schneider
  • 2019 | Buch

    Kompendium der Psychotherapie

    Für Ärzte und Psychologen

    Dieses Werk wendet sich an Ärzte und Psychologen, die an psychiatrischen und psychosomatischen Kliniken oder an Psychotherapeutischen Ausbildungsinstituten arbeiten und in den vorhandenen Lehrbüchern der Psychotherapie den Brückenschlag zur …

    Herausgeber:
    Tilo Kircher
Bildnachweise