Trazodone effects on developing brain.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
01 02 2021
01 02 2021
Historique:
received:
06
09
2020
accepted:
14
01
2021
revised:
06
01
2021
entrez:
2
2
2021
pubmed:
3
2
2021
medline:
29
6
2021
Statut:
epublish
Résumé
Trazodone (TRZ) is a commonly prescribed antidepressant with significant off-label use for insomnia. A recent drug screening revealed that TRZ interferes with sterol biosynthesis, causing elevated levels of sterol precursor 7-dehydrocholesterol (7-DHC). Recognizing the well-documented, disruptive effect of 7-DHC on brain development, we designed a study to analyze TRZ effects during pregnancy. Utilizing an in vivo model and human biomaterial, our studies were designed to also account for drug interactions with maternal or offspring Dhcr7 genotype. In a maternal exposure model, we found that TRZ treatment increased 7-DHC and decreased desmosterol levels in brain tissue in newborn pups. We also observed interactions between Dhcr7 mutations and maternal TRZ exposure, giving rise to the most elevated toxic oxysterols in brains of Dhcr7
Identifiants
pubmed: 33526772
doi: 10.1038/s41398-021-01217-w
pii: 10.1038/s41398-021-01217-w
pmc: PMC7851398
doi:
Substances chimiques
Cholesterol
97C5T2UQ7J
Oxidoreductases Acting on CH-CH Group Donors
EC 1.3.-
Trazodone
YBK48BXK30
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
85Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : MH110636
Organisme : NIGMS NIH HHS
ID : U54 GM115458
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ID : HD064727
Organisme : NICHD NIH HHS
ID : R01 HD064727
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH067234
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES028269
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD103537
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110636
Pays : United States
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