PXD064537-1

PXD064537 is an original dataset announced via ProteomeXchange.

Title	Intermittent Fasting Reprograms the Brain Proteome to Prevent Synaptic Degeneration and Cognitive Impairment in Vascular Dementia
Description	Vascular dementia (VaD), driven by chronic cerebral hypoperfusion (CCH), leads to synaptic degeneration and cognitive decline, yet mechanisms linking vascular dysfunction to synaptic loss remain unclear. Intermittent fasting (IF) has emerged as a potential intervention, but its effects on synaptic integrity in VaD are unknown. Using the bilateral common carotid artery stenosis (BCAS) mouse model, we demonstrate that a 16-hour IF regimen preserves cognitive function and cortical synaptic density despite persistent hypoperfusion. Behavioral assays revealed that IF prevented spatial memory deficits in BCAS mice, while electron microscopy confirmed synaptic preservation without altering baseline architecture. Surprisingly, synaptic protein levels remained unchanged, suggesting IF protects synaptic function rather than abundance. Proteomic profiling uncovered dynamic hippocampal adaptations under IF, including upregulation of synaptic stabilizers, enhanced GABAergic signaling, and suppression of neuroinflammatory mediators. IF also attenuated microglial engulfment of synapses, indicating modulation of complement-mediated pruning. Temporal pathway analysis revealed IF’s multi-phase neuroprotection: early synaptic reinforcement, mid-phase metabolic optimization, and late-phase suppression of chronic neuroinflammation. These findings establish IF as a potent modulator of synaptic resilience in VaD, acting through coordinated preservation of synaptic structure, inhibition of inflammatory synapse loss, and metabolic reprogramming. Our results highlight IF’s potential as a non-pharmacological strategy to combat vascular cognitive impairment by targeting the synaptic vulnerability underlying dementia progression.
HostingRepository	PRIDE
AnnounceDate	2025-09-08
AnnouncementXML	Submission_2025-09-07_23:26:22.721.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nishat Tabassum
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-02 22:28:26	ID requested
⏵ 1	2025-09-07 23:26:23	announced

10.7150/thno.119422;

Tabassum NI, Selvaraji S, Fan Y, Lim VJ, Cheng X, Peng X, Arora A, Rajeev V, Ratcliffe J, Johnson CJ, Datta KK, Lowe R, Ebrahimi M, Dinh QN, De Silva TM, Sobey CG, Wong P, Weng EF, Jo DG, Chen CP, Lai MKP, Arumugam TV, Intermittent fasting reprograms the brain proteome to prevent synaptic degeneration and cognitive impairment in vascular dementia. Theranostics, 15(16):8429-8450(2025) [pubmed]

submitter keyword: Vascular dementia, Intermittent fasting, Synapse, mouse hippocampus

Thiruma V. Arumugam
contact affiliation	Department of Microbiology, Anatomy, Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, Australia. La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia.
contact email	g.arumugam@latrobe.edu.au
lab head
Nishat Tabassum
contact affiliation	Department of Microbiology, Anatomy, Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, Australia.
contact email	n.tabassum@latrobe.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD064537
     1. Label: PRIDE project
     2. Name: Intermittent Fasting Reprograms the Brain Proteome to Prevent Synaptic Degeneration and Cognitive Impairment in Vascular Dementia