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Neural Plasticity
Volume 2015 (2015), Article ID 825157, 14 pages
Research Article

Limited Effects of an eIF2αS51A Allele on Neurological Impairments in the 5xFAD Mouse Model of Alzheimer’s Disease

1German Center for Neurodegenerative Diseases (DZNE), Ludwig Erhard Allee 2, 53175 Bonn, Germany
2Federal Institute for Drugs and Medical Devices (BfArM), Kurt Georg Kiesinger Allee 3, 53175 Bonn, Germany
3Department of Psychiatry and Psychotherapy, University of Cologne, Kerpener Straße 62, 50937 Köln, Germany
4Institute of Molecular Psychiatry, University of Bonn, Sigmund Freud Straße 25, 53125 Bonn, Germany
5German Center for Neurodegenerative Diseases (DZNE), Fetscherstraße 105, 01307 Dresden, Germany

Received 17 December 2014; Revised 15 February 2015; Accepted 23 February 2015

Academic Editor: Clive R. Bramham

Copyright © 2015 Katharina Paesler et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Supplementary Material

Supplementary Figure 1. Enhanced phosphorylation of eIF2α in SHSY5Y cells incubated with DTT. Shown are p-eIF2α and eIF2α immunoblots performed on lysates of SHSY5Y cells that had been treated with vehicle or 2mM DTT for 15 or 60 min (n = 2 samples per condition). Densitometric quantification revealed the expected increase in eIF2α phosphorylation in SHSY5Y cells incubated with DTT. P-values refer to results of posthoc Tukey tests.

Supplementary Figure 2. The cholinergic system was not involved in the eIF2α+/S51A-related restoration of hyperactivity in 5xFAD mice. (A) Shown are micrographs of ChAT-immunoreactive neurons in the basal forebrain of wild-type, 5xFAD, 5xFAD;eIF2α+/S51A and eIF2α+/S51A mice. Scale bar = 150 μm. Stereological quantification of ChAT-immunoreactive neurons in the MS and VDB of the basal forebrain demonstrated no significant differences between the four groups of mice (n = 3 mice per group). (B) Shown are immunoblots of ChAT from hippocampal homogenates of wild-type, 5xFAD, 5xFAD;eIF2α+/S51A and eIF2α+/S51A mice (n = 5-7 mice per group). Data were analyzed using two-way ANOVAs with the between-subjects factors 5xFAD genotype and eIF2α genotype. Statistically significant differences (p < 0.05) are denoted by bold font. Bar graphs show mean ± SEM.

Supplementary Figure 3. The eIF2αS51A allele had limited effects on transcriptional dysregulation in 5xFAD mice. Differentially regulated transcripts (Benjamini Hochberg FDR, p < 0.02) with a fold change higher than 1.6 were subjected to hierarchical clustering to visualize gene expression changes between groups (n = 3 mice per genotype).

Supplementary Table 1. A gene ontology analysis (DAVID) revealed a significant enrichment of immune-related transcripts in gene set differentially expressed in 5xFAD hippocampus.

Supplementary Table 2. Ingenuity pathway analysis also indicated a substantial enrichment of genes related to immune and inflammatory processes in the gene set differentially expressed in 5xFAD hippocampus.

  1. Supplementary Figure 1
  2. Supplementary Figure 2
  3. Supplementary Figure 3
  4. Supplementary Table 1
  5. Supplementary Table 2