PXD072113-1

PXD072113 is an original dataset announced via ProteomeXchange.

Title	Altered Brain Energy Metabolism in the APPPS1 Alzheimer’s Mouse Model during Anesthesia
Description	Background: Synaptic transmission and network activity rely on high ATP turnover. Impairments in cerebral energy metabolism are increasingly recognized as central to aging and the pathogenesis of Alzheimer’s disease (AD). AD is related to elevated risk for perioperative neurological complications, including postoperative delirium and further cognitive deterioration. However, the interaction between metabolic vulnerability and anesthetic exposure remains incompletely understood. Methods: We investigated cortical metabolic responses and potassium homeostasis in acute brain slices from wild-type (WT) and AD-like APPPS1 transgenic mice, which were either exposed to isoflurane or left untreated. Glia cells were assessed by staining microglia and astrocytes. Measurements of the cerebral metabolic rate of oxygen (CMRO2), extracellular potassium ([K+]o) dynamics, and proteomic profiling were integrated with computational modeling to assess oxidative metabolism and anesthetic effects under different conditions. Results: APPPS1 mice exhibited reduced CMRO2 and attenuated neuronal activity compared to age-matched WT animals, showing sex-specific differences. Proteomic analysis revealed the downregulation of key mitochondrial and glycolytic enzymes, indicating an impaired capacity for ATP generation. Exposure to isoflurane further suppressed CMRO2, with a more pronounced effect in the APPPS1 brain tissue, while glia cells exhibited no acute changes. Additionally, isoflurane exacerbated deficits in [K+]o clearance, highlighting impaired ion homeostasis under anesthesia. Conclusions: Our findings demonstrate that AD-like pathology is associated with a significant decline in oxidative metabolism and ATP availability. These deficits are exacerbated by anesthetic exposure, contributing to impaired potassium regulation. This suggests that diminished metabolic flexibility may underlie increased anesthetic vulnerability and postoperative complications in AD.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-08_05:09:43.134.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anja Freiwald
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	iodoacetamide derivatized residue
Instrument	ZenoTOF 7600

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-17 13:38:35	ID requested
⏵ 1	2026-06-08 05:09:43	announced

Dataset with its publication pending

submitter keyword: None

Nikolaus Berndt
contact affiliation	Charité – Universitätsmedizin Berlin, Germany
contact email	nikolaus.berndt@charite.de
lab head
Anja Freiwald
contact affiliation	Charité
contact email	anja.freiwald@charite.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD072113
     1. Label: PRIDE project
     2. Name: Altered Brain Energy Metabolism in the APPPS1 Alzheimer’s Mouse Model during Anesthesia