Sex-specific declines in cholinergic-targeting tRNA fragments in the nucleus accumbens in Alzheimer's disease.
Alzheimer's disease
bioinformatics
cholinergic system
cognitive impairment
sex-differences
tRNA fragments (tRFs)
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
received:
23
02
2023
accepted:
21
03
2023
pmc-release:
09
11
2024
medline:
16
11
2023
pubmed:
9
5
2023
entrez:
9
5
2023
Statut:
ppublish
Résumé
Females with Alzheimer's disease (AD) suffer accelerated dementia and loss of cholinergic neurons compared to males, but the underlying mechanisms are unknown. Seeking causal contributors to both these phenomena, we pursued changes in transfer RNS (tRNA) fragments (tRFs) targeting cholinergic transcripts (CholinotRFs). We analyzed small RNA-sequencing (RNA-Seq) data from the nucleus accumbens (NAc) brain region which is enriched in cholinergic neurons, compared to hypothalamic or cortical tissues from AD brains; and explored small RNA expression in neuronal cell lines undergoing cholinergic differentiation. NAc CholinotRFs of mitochondrial genome origin showed reduced levels that correlated with elevations in their predicted cholinergic-associated mRNA targets. Single-cell RNA seq from AD temporal cortices showed altered sex-specific levels of cholinergic transcripts in diverse cell types; inversely, human-originated neuroblastoma cells under cholinergic differentiation presented sex-specific CholinotRF elevations. Our findings support CholinotRFs contributions to cholinergic regulation, predicting their involvement in AD sex-specific cholinergic loss and dementia.
Identifiants
pubmed: 37158312
doi: 10.1002/alz.13095
pmc: PMC10632545
mid: NIHMS1889309
doi:
Substances chimiques
Cholinergic Agents
0
RNA
63231-63-0
RNA, Transfer
9014-25-9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5159-5172Subventions
Organisme : NIA NIH HHS
ID : P30 AG072975
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046152
Pays : United States
Organisme : NIH HHS
ID : U01AG46152
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG061356
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG017917
Pays : United States
Organisme : NIH HHS
ID : U01AG61356
Pays : United States
Organisme : NIH HHS
ID : R01AG15819
Pays : United States
Organisme : NIH HHS
ID : R01AG17917
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Organisme : NIH HHS
ID : P30AG10161
Pays : United States
Organisme : NIH HHS
ID : 5P01AG014449-21
Pays : United States
Organisme : NIH HHS
ID : P30AG72975
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG014449
Pays : United States
Organisme : NIH HHS
ID : P30AG10161
Pays : United States
Organisme : NIH HHS
ID : P30AG72975
Pays : United States
Organisme : NIH HHS
ID : R01AG15819
Pays : United States
Organisme : NIH HHS
ID : R01AG17917
Pays : United States
Organisme : NIH HHS
ID : U01AG46152
Pays : United States
Organisme : NIH HHS
ID : U01AG61356
Pays : United States
Organisme : NIH HHS
ID : 5P01AG014449-21
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
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