PXD052521

PXD052521 is an original dataset announced via ProteomeXchange.

Title	Early life exposure to deltamethrin impairs synaptic function by altering the brain derived extracellular vesicle proteome
Description	Pyrethroid pesticides, widely used in agriculture and households, have been associated with neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). While behavioral effects of pyrethroid exposure have been previously reported, the underlying mechanisms remain unclear. Here, we hypothesized that exposure to deltamethrin (DM), a widely used pyrethroid pesticide known for its neurotoxicity during early developmental stages, induces brain dysfunction through alterations in brain-derived extracellular vesicle (BDEV) signaling. Using a well-established rodent model of early life DM exposure within the recommended no observable effect level, we isolated BDEVs from postnatal 30-day-old vehicle-exposed (control) and DM-exposed mice using a differential sucrose density gradient. Following ZetaView nanoparticle tracking and electron microscopy characterization, quantitative mass spectrometry-based proteomics revealed 89 differentially expressed proteins (DEPs) in BDEVs from DM exposed animals compared to control BDEVs. Bioinformatic analysis identified convergence of DEPs on pathways associated with mitochondrial function and synaptic plasticity. PKH67-green conjugated BDEVs derived from either control or DM-exposed mice were bilaterally injected intracerebroventricularly into naïve adult mice, and the brain distribution of labeled BDEVs was verified prior to extracellular field recording experiments. Strikingly, while CA3 Schaffer’s collaterals to CA1 basal synaptic transmission was intact in both groups, long-term synaptic potentiation, a functional correlate of learning and memory, was intact in control BDEVs, but absent in naïve mice receiving BDEVs from DM exposed mice. Overall, our studies reveal a potential novel mechanism by which DM exerts neurotoxic effects on synaptic functions associated with neurodevelopmental disorders, conveyed via differentially regulated BDEVs signaling.
HostingRepository	PRIDE
AnnounceDate	2026-08-24
AnnouncementXML	Submission_2026-08-23_16:20:20.917.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gurudutt Pendyala
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-23 09:04:40	ID requested
⏵ 1	2026-08-23 16:20:21	announced

Koff L, Di Re J, Chand S, Avchalumov Y, Nguyen NM, Baumgartner TJ, Singh AK, Goode NA, Marosi M, Hallberg LM, Ameredes BT, Green TA, Yelamanchili SV, Pendyala G, Laezza F, Early Life Exposure to Deltamethrin Impairs Synaptic Function by Altering the Brain-Derived Extracellular Vesicle Proteome. Mol Cell Proteomics, 24(2):100902(2025) [pubmed]

10.1016/j.mcpro.2024.100902;

submitter keyword: neurodevelopment, hippocampus, pyrethroid, Hebbian plasticity,exosome

Gurudutt Pendyala
contact affiliation	University of Nebraska Medical Center
contact email	gpendyala@unmc.edu
lab head
Gurudutt Pendyala
contact affiliation	University of Nebraska Medical Center
contact email	gpendyala@unmc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052521
     1. Label: PRIDE project
     2. Name: Early life exposure to deltamethrin impairs synaptic function by altering the brain derived extracellular vesicle proteome