PXD034176

PXD034176 is an original dataset announced via ProteomeXchange.

Title	Activation of hypothalaActivation of hypothalamic-enhanced adult-born neurons is sufficient to restore cognitive and noncognitive function in Alzheimer's diseasemic-enhanced adult-born neurons is sufficient to restore cognitive and noncognitive function in Alzheimer's diseaseActivation of hypothalamic-enhanced adult-born neurons is sufficient to restore cognitive and noncognitive function in Alzheimer's disease
Description	Patients with Alzheimer’s disease (AD) exhibit progressive memory loss, depression, and anxiety, accompanied by impaired adult hippocampal neurogenesis (AHN). Whether modulating AHN is sufficient to improve these cognitive and noncognitive symptoms in AD remains elusive. Here we report that chronic stimulation of hypothalamic supramammillary nucleus (SuM) during early AD restores AHN in an otherwise impaired neurogenic niche. Strikingly, activation of SuM-enhanced adult-born neurons (ABNs) is sufficient to restore memory and emotion deficits in 5×FAD mice. Interestingly, activation of SuM-enhanced ABNs in AD mice increases CA3 and CA1 activity. To probe ABN-activity-dependent changes, we performed quantitative phosphoproteomics and found activation of SuM-enhanced ABNs promotes activation of the canonical pathways related to synaptic plasticity and microglia phagocytosis. Functional assays further confirm increased CA1 long-term potentiation and enhanced microglia phagocytosis of plaques upon activation of SuM-enhanced ABNs. Our findings reveal a robust AHN-promoting strategy that is sufficient to restore AD-associated deficits and highlight ABN-activity-dependent mechanisms underlying functional improvement in AD.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:56:32.473.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ling Xie
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-29 13:43:14	ID requested
1	2023-03-08 11:38:53	announced
⏵ 2	2023-11-14 08:56:32	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: mouse, hippocampus, LC-MS, phosphoproteom

Juan Song
contact affiliation	Department of Pharmacology University of North Carolina
contact email	juansong@email.unc.edu
lab head
Ling Xie
contact affiliation	UNC at Chapel Hill
contact email	xiel@email.unc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034176
     1. Label: PRIDE project
     2. Name: Activation of hypothalaActivation of hypothalamic-enhanced adult-born neurons is sufficient to restore cognitive and noncognitive function in Alzheimer's diseasemic-enhanced adult-born neurons is sufficient to restore cognitive and noncognitive function in Alzheimer's diseaseActivation of hypothalamic-enhanced adult-born neurons is sufficient to restore cognitive and noncognitive function in Alzheimer's disease