Dataset Information

Limited effects of an eIF2αS51A allele on neurological impairments in the 5xFAD mouse model of Alzheimer’s disease

ABSTRACT: Transcriptome analysis of hippocampal RNA samples from wild-type, 5xFAD, 5xFAD;eIF2α+/S51A and eIF2α+/S51A mice Our transcriptome analyses showed clear transcriptional alterations in hippocampi of 5xFAD compared to wild type mice that were not corrected by the eIF2αS51A allele.

ORGANISM(S): Mus musculus

PROVIDER: GSE50521 | GEO | 2013/09/10

SECONDARY ACCESSION(S): PRJNA217853

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Alzheimer’s disease (AD) is an unremitting neurodegenerative disorder characterized by cerebral amyloid-β (Aβ) accumulation and gradual decline in cognitive function. Changes in brain energy metabolism arise in the preclinical phase of AD, suggesting an important metabolic component of early AD pathology. Neurons and astrocytes function in close metabolic collaboration, which is essential for the recycling of neurotransmitters in the synapse. However, how this metabolic interplay may be affected during the early stages of AD development has not been sufficiently investigated. Here, we provide an integrative analysis of cellular metabolism during the early stages of Aβ accumulation in the cerebral cortex and hippocampus of the 5xFAD mouse model of AD. Our electrophysiological examination revealed an increase in spontaneous excitatory signaling in hippocampal brain slices of 5xFAD mice. This hyperactive neuronal phenotype coincided with decreased hippocampal TCA cycle metabolism mapped by stable 13C isotope tracing. Particularly, reduced astrocyte TCA cycle activity led to decreased glutamine synthesis, in turn hampering neuronal GABA synthesis in the 5xFAD hippocampus. In contrast, cerebral cortical slices of 5xFAD mice displayed an elevated capacity for oxidative glucose metabolism suggesting a metabolic compensation. When we explored the brain proteome and metabolome of the 5xFAD mice, we found limited changes, supporting that the functional metabolic disturbances between neurons and astrocytes are early events in AD pathology. In addition, we show that synaptic mitochondrial and glycolytic function was impaired selectively in the 5xFAD hippocampus, whereas non-synaptic mitochondrial function was maintained. These findings were supported by ultrastructural analyses demonstrating disruptions in mitochondrial morphology, particularly in the 5xFAD hippocampus. Collectively, our study reveals complex region and cell specific metabolic adaptations, in the early stages of amyloid pathology, which may be fundamental for the progressing synaptic dysfunction in AD.

Dataset Information

Limited effects of an eIF2αS51A allele on neurological impairments in the 5xFAD mouse model of Alzheimer’s disease

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure