Dataset Information

Neuropeptides in the Extracellular Space of the Mouse Cortex Measured by In Vivo Nanodialysis Probe

ABSTRACT: Neuropeptides are key neuromodulators in the central nervous system that shape sensory processing, yet their extracellular dynamics in the somatosensory cortex (S1) remain poorly understood. This study applies an innovative membrane-free silicon nanodialysis (ND) probe coupled with liquid chromatography-mass spectrometry (LC-MS) to analyze the extracellular neuropeptidome in the mouse S1 with spatial resolution down to 100 μm. Localized in vivo sampling identified extracellular peptides from secretogranin-1, ProSAAS, pro-opiomelanocortin (POMC), and others. Minimal tissue damage, enabled by probe dimensions of 75×15 μm², resulted in an absence of structural peptides in the dialysate indicating low intracellular contamination. Many detected secretory peptides correlated with strong local mRNA expression; however, the detection of POMC-derived peptides, despite negligible local expression, suggests long-distance peptide transport or extracellular processing. To expand peptide identification, a discovery-to-targeted peptidomic approach was developed, revealing 46 peptides from 24 proteins in dialysate samples, including 10 proteins with low local expression. Complementary S1 tissue analysis confirmed POMC peptides and showed that 17% of 304 prohormone-derived peptides had low local expression. These results uncover a complex extracellular peptide landscape shaped by both local and long-distance signaling. By overcoming the limitations of traditional microdialysis, this approach advances the understanding of neuropeptide signaling in cortical function.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Keyin Li

LAB HEAD: Jonathan V. Sweedler

PROVIDER: PXD066497 | Pride | 2025-09-29

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Mouse_brain_peptidome_3X_Slot1-13_1_3292.d.zip	Other
	Mouse_brain_peptidome_3X_Slot1-13_1_3292.mgf	Mgf
	checksum.txt	Txt
	dialysateDDA.mzid	Mzid
	dialysateDDApeptide.csv	Csv

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Publications

Neuropeptides in the Extracellular Space of the Mouse Cortex Measured In Vivo by Nanodialysis Probe Coupled with LC-MS.

Li Keyin K Shi Weihua W Tan Yanqi Y Ding Yu Y Armstrong Alex G AG Vlasov Yurii Y Sweedler Jonathan V JV

Angewandte Chemie (International ed. in English) 20250811 39

Neuropeptides are key neuromodulators in the central nervous system that shape sensory processing, yet their extracellular dynamics in the somatosensory cortex (S1) remain poorly understood. This study applies an innovative membrane-free silicon nanodialysis (ND) probe coupled with liquid chromatography-mass spectrometry (LC-MS) to analyze the extracellular neuropeptidome in the mouse S1 with spatial resolution down to 100 µm. Localized in vivo sampling identified extracellular peptides from sec ...[more]

PMID: 40787760

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