PXD073765-1

PXD073765 is an original dataset announced via ProteomeXchange.

Title	mPFC Synaptosome Proteomics Reveals Novel Pathways and Muscarinic Receptor Changes in a Learned Helplessness Mouse Model
Description	Stressful events are a leading factor in development of depression. The medial prefrontal cortex (mPFC) is strongly associated with depression etiology and exposure to uncontrollable stressors results in synaptic dysfunction and loss. Learned helplessness is a behavioral paradigm that measures effects of repeated exposure to uncontrollable, inescapable stress on later responses to escapable stress. We therefore performed a proteomic analysis of mPFC synaptosomes in a mouse learned helplessness model to identify molecular changes that could contribute to functional consequences of inescapable stress. Male and female mice were evaluated at baseline and following exposure to escapable or inescapable stress followed by an active avoidance test. Label-free mass spectrometry followed by pathway and protein-protein interaction network analyses identified alterations in signaling pathways involved in energy metabolism, neurotransmitter signaling, and protein shuttling. Furthermore, phosphoproteomics revealed alterations related to synaptic function, neurotransmitter signaling and protein internalization, as well as changes in activity of kinases previously identified as mediators of antidepressant efficacy (GSK3B) and receptor internalization (ADRBK1). We more deeply examined alterations in the Acetylcholine Receptor Signaling Pathway, and identified muscarinic receptor proteins (Chrm1, Chrm2, Chrm4) and key proteins involved in their translocation to and from the membrane. These results identify substantial changes in the mPFC proteome following exposure to inescapable stressors. In addition, mPFC muscarinic cholinergic signaling is well placed to mediate responses to an inescapable stressor. This proteomic study will be useful in guiding studies of human mPFC relevant to depression
HostingRepository	PRIDE
AnnounceDate	2026-04-20
AnnouncementXML	Submission_2026-04-19_16:10:45.766.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	TuKiet Lam
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-29 04:53:33	ID requested
⏵ 1	2026-04-19 16:10:46	announced

10.1523/eneuro.0030-26.2026;

Abdulla ZI, Garcia-Milian R, Giahyue E, Fertuzinhos S, Collin F, Wang W, Lam TT, Nairn AC, Picciotto MR, mPFC Synaptosome Proteomics Reveals Novel Pathways and Muscarinic Receptor Changes in a Learned Helplessness Mouse Model. eNeuro, ():(2026) [pubmed]

submitter keyword: mPFC, Acetylcholine, Major Depressive Disorder, Stress Models, Learned Helplessness, Muscarinic Receptors, Proteomics

TuKiet Lam
contact affiliation	Keck MS & Proteomics Resource Yale School of Medicine
contact email	tukiet.lam@yale.edu
lab head
TuKiet Lam
contact affiliation	Yale University
contact email	tukiet.lam@yale.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD073765
     1. Label: PRIDE project
     2. Name: mPFC Synaptosome Proteomics Reveals Novel Pathways and Muscarinic Receptor Changes in a Learned Helplessness Mouse Model