In:
Neural Plasticity, Hindawi Limited, Vol. 2015 ( 2015), p. 1-14
Kurzfassung:
Alzheimer’s disease (AD) has been associated with increased phosphorylation of the translation initiation factor 2 α (eIF2 α ) at serine 51. Increased phosphorylation of eIF2 α alters translational control and may thereby have adverse effects on synaptic plasticity, learning, and memory. To analyze if increased levels of p-eIF2 α indeed promote AD-related neurocognitive impairments, we crossed 5xFAD transgenic mice with an e I F 2 α S 51 A knock-in line that expresses the nonphosphorylatable eIF2 α variant e I F 2 α S 51 A . 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 e I F 2 α S 51 A allele. Telemetric intracranial EEG recordings revealed no measurable effects of the e I F 2 α S 51 A allele on 5xFAD-associated epileptic activity. Microarray-based transcriptome analyses showed clear transcriptional alterations in 5xFAD hippocampus that were not corrected by the e I F 2 α S 51 A allele. In contrast to prior studies, our immunoblot analyses did not reveal increased levels of p-eIF2 α in the hippocampus of 5xFAD mice, suggesting that elevated p-eIF2 α levels are not a universal feature of AD models. Collectively, our data indicate that 5xFAD-related pathologies do not necessarily require hyperphosphorylation of eIF2 α to emerge; they also show that heterozygosity for the nonphosphorylatable e I F 2 α S 51 A allele has limited effects on 5xFAD-related disease manifestations.
Materialart:
Online-Ressource
ISSN:
2090-5904
,
1687-5443
Sprache:
Englisch
Verlag:
Hindawi Limited
Publikationsdatum:
2015
ZDB Id:
2236872-3
