PXD045844

PXD045844 is an original dataset announced via ProteomeXchange.

Title	Sex Differences in Single Neuron Function and Proteomics Profiles Examined by Patch-Clamp and Mass Spectrometry in the Locus Coeruleus of the Adult Mouse
Description	Aims: This study aimed to identify and characterize the intrinsic properties of locus coeruleus (LC) noradrenergic neurons in male and female mice using a genetic approach. We also sought to investigate sex-specific differences in membrane properties, action potential generation, and protein expression profiles to understand the mechanisms underlying neuronal excitability variations. Methods: Utilizing a genetic mouse model by crossing Dbhcre knock-in mice with tdTomato Ai14 transgenic mice, LC neurons were identified using fluorescence microscopy. Neuronal properties, including capacitance, action potential frequency, and rheobase, were assessed using patch-clamp recordings. Spontaneous and evoked activity between sexes was compared. Proteomic analyses of individual LC neuron soma was conducted using mass-spectrometry to discern protein expression profiles. Results: Female LC noradrenergic neurons displayed greater membrane capacitance than those in male mice. Male LC neurons demonstrated greater spontaneous and evoked action potential generation compared to females. Male LC neurons exhibited a lower rheobase and achieved higher peak frequencies with similar current injections. Proteomic analysis revealed inherent differences in protein expression profiles between sexes, with male mice displaying a notably larger unique protein set compared to females. Notably, pathways pertinent to protein synthesis, degradation, and recycling, such as EIF2 and glucocorticoid receptor signaling, showed reduced expression in females. Conclusions: Male LC noradrenergic neurons exhibit higher intrinsic excitability compared to those from females. The discernible sex-based differences in excitability could be ascribed to varying protein expression profiles, especially within pathways that regulate protein synthesis and degradation. This study lays the groundwork for future studies focusing on the interplay between proteomics and neuronal function examined in individual cells.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:42:25.794.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD045844
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Jingyun Lee
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-01 22:40:52	ID requested
1	2024-05-24 01:14:30	announced
⏵ 2	2024-10-22 06:42:31	announced	2024-10-22: Updated project metadata.

10.1111/apha.14123;

Lee J, Wang ZM, Messi ML, Milligan C, Furdui CM, Delbono O, Sex differences in single neuron function and proteomics profiles examined by patch-clamp and mass spectrometry in the locus coeruleus of the adult mouse. Acta Physiol (Oxf), 240(4):e14123(2024) [pubmed]

10.6019/PXD045844;

submitter keyword: neuronal excitability, single-cell proteomics,Noradrenergic neurons, locus coeruleus, sex-differences

Osvaldo Delbono
contact affiliation	Department of Internal Medicine, Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, United States
contact email	odelbono@wakehealth.edu
lab head
Jingyun Lee
contact affiliation	Wake Forest Baptist Health
contact email	jilee@wakehealth.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045844
     1. Label: PRIDE project
     2. Name: Sex Differences in Single Neuron Function and Proteomics Profiles Examined by Patch-Clamp and Mass Spectrometry in the Locus Coeruleus of the Adult Mouse