PXD024325-2

PXD024325 is an original dataset announced via ProteomeXchange.

Title	Sex-Specific Microglia Defects in the Neuroligin-4 Knock-Out Mouse Model of Autism Spectrum Disorder
Description	Neuroligin-4 (NL4) loss-of-function mutations are strongly associated with monogenic heritable abnormalities linked with Autism Spectrum Disorder (ASD). NL4 mutation in mice causes ASD related alterations in both, the synaptic and behavioral phenotype. Since microglia closely regulate synaptic development and are implicated as key players in ASD development and progression, we here studied microglial properties in the NL4-/- mouse model. We show that loss of NL4 caused altered behavior and impaired hippocampal gamma oscillations predominantly in male mice. In parallel, microglial density, morphology, and response to injury specifically in the CA3 region of the hippocampus were altered in NL4-deficient males only. A transcriptomic and proteomic analysis revealed a strong impact of sexual dimorphism on molecular alterations in microglia of NL4-deficient compared to wildtype mice. Estrogen application in male NL4-/- animals partially restored the impaired social behavior and the altered microglial phenotype. Together, these results indicate that loss of NL4 affects not only neuronal network activity and behavior, but changes in addition the phenotype of microglia in a sex-specific manner that could be targeted by estrogen treatment.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:06:58.334.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Oliver Popp
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-23 22:53:09	ID requested
1	2023-10-24 11:02:14	announced
⏵ 2	2023-11-14 09:06:59	announced	2023-11-14: Updated project metadata.
3	2024-10-22 06:08:29	announced	2024-10-22: Updated project metadata.

Guneykaya D, Ugursu B, Logiacco F, Popp O, Feiks MA, Meyer N, Wendt S, Semtner M, Cherif F, Gauthier C, Madore C, Yin Z, Ç, ı, nar Ö, Arslan T, Gerevich Z, Mertins P, Butovsky O, Kettenmann H, Wolf SA, Sex-specific microglia state in the Neuroligin-4 knock-out mouse model of autism spectrum disorder. Brain Behav Immun, 111():61-75(2023) [pubmed]

submitter keyword: Sex difference, Gamma oscillation, Estrogen, Microglia,Autism spectrum disorder

Susanne A. Wolf
contact affiliation	MDC, Cellular Neuroscience Charitè, Ophthalmology
contact email	susanne.wolf@charite.de
lab head
Oliver Popp
contact affiliation	MDC Berlin
contact email	oliver.popp@mdc-berlin.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/10/PXD024325

PRIDE project URI

• PRIDE
  1. PXD024325
     1. Label: PRIDE project
     2. Name: Sex-Specific Microglia Defects in the Neuroligin-4 Knock-Out Mouse Model of Autism Spectrum Disorder