Deficient astrocyte metabolism impairs glutamine synthesis and neurotransmitter homeostasis in a mouse model of Alzheimer's disease.

Deficient astrocyte metabolism impairs glutamine synthesis and neurotransmitter homeostasis in a mouse model of Alzheimer's disease.
Neurobiol Dis. 2020 Nov 23;:105198
Authors: Andersen JV, Christensen SK, Westi EW, Diaz-delCastillo M, Tanila H, Schousboe A, Aldana BI, Waagepetersen HS
Abstract
Alzheimer's disease (AD) leads to cerebral accumulation of insoluble amyloid-β plaques causing synaptic dysfunction and neuronal death. Neurons rely on astrocyte-derived glutamine for replenishment of the amino acid neurotransmitter pools. Perturbations of astrocyte glutamine synthesis have been described in AD, but whether this functionally affects neuronal neurotransmitter synthesis is not known. Since the synthesis and recycling of neurotransmitter glutamate and GABA are intimately coupled to cellular metabolism, the aim of this study was to provide a functional investigation of neuronal and astrocytic energy and neurotransmitter metabolism in AD. To achieve this, we incubated acutely isolated cerebral cortical and hippocampal slices from 8-month-old female 5xFAD mice, in the presence of 13C isotopically enriched substrates, with subsequent gas chromatography-mass spectrometry (GC-MS) analysis. A prominent neuronal hypometabolism of [U13C]glucose was observed in the hippocampal slices of the 5xFAD mice. Investigating astrocyte metabolism, using [1,2-13C]acetate, revealed a marked reduction in glutamine synthesis, which directly hampered ne...

Source: Neurobiology of Disease - November 23, 2020 Category: Neurology Authors: Andersen JV, Christensen SK, Westi EW, Diaz-delCastillo M, Tanila H, Schousboe A, Aldana BI, Waagepetersen HS Tags: Neurobiol Dis Source Type: research