2019
DOI: 10.2139/ssrn.3433807
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Impairment of Glycolysis-Derived L-Serine Production in Astrocytes Contributes to Cognitive Deficits in Alzheimer's Disease

Abstract: Alteration of brain aerobic glycolysis is often observed early in the course of Alzheimer's disease (AD). Whether and how such metabolic dysregulation contributes to both synaptic plasticity and behavioral deficits in AD is not known. Here, we show that the astrocytic L-serine biosynthesis pathway, which branches from glycolysis, is impaired in young AD mice and in AD patients. L-serine is the precursor of D-serine, a co-agonist of synaptic NMDA receptors (NMDARs) required for synaptic plasticity. Accordingly,… Show more

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Cited by 26 publications
(39 citation statements)
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“…Reactive microglia may shift astrocyte signaling from physiological to pathological by increasing production of tumor necrosis factor α (TNFα), thus altering synaptic functions and behavior 57 . Functions lost or altered in reactive astrocytes include neurotransmitter and ion buffering in mouse HD models 58 , communication via gap junctions in the sclerotic hippocampus of patients with epilepsy 59 , phagocytic clearance of dystrophic neurites 60 , and metabolic coupling by glycolysis-derived d-serine 61 and lactate 62 in mouse AD models. The excessive release of GABA by reactive astrocytes in AD 63 and Parkinson's disease 64 Transcriptomics and A1-A2 classification.…”
Section: Impact In Cns Diseasesmentioning
confidence: 99%
“…Reactive microglia may shift astrocyte signaling from physiological to pathological by increasing production of tumor necrosis factor α (TNFα), thus altering synaptic functions and behavior 57 . Functions lost or altered in reactive astrocytes include neurotransmitter and ion buffering in mouse HD models 58 , communication via gap junctions in the sclerotic hippocampus of patients with epilepsy 59 , phagocytic clearance of dystrophic neurites 60 , and metabolic coupling by glycolysis-derived d-serine 61 and lactate 62 in mouse AD models. The excessive release of GABA by reactive astrocytes in AD 63 and Parkinson's disease 64 Transcriptomics and A1-A2 classification.…”
Section: Impact In Cns Diseasesmentioning
confidence: 99%
“…This device was then optimized in terms of stability and sensitivity by immobilizing RgDAAO using poly(ethyleneglycol)diglycidyl ether [ 73 ]. This microbiosensor was widely used over the years to investigate the role of D-Ser in the brain under physiological and pathological conditions [ 72 , 80 , 81 , 82 , 83 ].…”
Section: Detection Of D-aas For Biomedical Applicationsmentioning
confidence: 99%
“…A large cohort of genes involved in metabolism are induced after traumatic brain injury (Arneson et al, 2018). Impairment of glycolysis-derived metabolites in astrocytes contributes to cognitive deficits in Alzheimer's disease (Le Douce et al, 2020). Previously, mitochondria function and energy metabolism have not been compared directly between human and mouse for any cell type of the central nervous system, to the best of our knowledge.…”
Section: Species Differences In Energy Metabolism In Astrocytes and Omentioning
confidence: 99%