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Neural Plasticity
Volume 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.


Alzheimer’s disease (AD) has been associated with increased phosphorylation of the translation initiation factor 2α (eIF2α) at serine 51. Increased phosphorylation of eIF2α alters translational control and may thereby have adverse effects on synaptic plasticity, learning, and memory. To analyze if increased levels of p-eIF2α indeed promote AD-related neurocognitive impairments, we crossed 5xFAD transgenic mice with an knock-in line that expresses the nonphosphorylatable eIF2α variant . Behavioral assessment of the resulting mice revealed motor and cognitive deficits in 5xFAD mice that were, with the possible exception of locomotor hyperactivity, not restored by the allele. Telemetric intracranial EEG recordings revealed no measurable effects of the allele on 5xFAD-associated epileptic activity. Microarray-based transcriptome analyses showed clear transcriptional alterations in 5xFAD hippocampus that were not corrected by the allele. In contrast to prior studies, our immunoblot analyses did not reveal increased levels of p-eIF2α in the hippocampus of 5xFAD mice, suggesting that elevated p-eIF2α levels are not a universal feature of AD models. Collectively, our data indicate that 5xFAD-related pathologies do not necessarily require hyperphosphorylation of eIF2α to emerge; they also show that heterozygosity for the nonphosphorylatable allele has limited effects on 5xFAD-related disease manifestations.