Back to Search Start Over

Long-Term Fluoxetine Administration Causes Substantial Lipidome Alteration of the Juvenile Macaque Brain

Authors :
Anna Tkachev
Elena Stekolshchikova
Daniil M. Bobrovskiy
Nickolay Anikanov
Polina Ogurtsova
Dong Ik Park
Anja K. E. Horn
Daria Petrova
Ekaterina Khrameeva
Mari S. Golub
Christoph W. Turck
Philipp Khaitovich
Source :
International Journal of Molecular Sciences, Vol 22, Iss 15, p 8089 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Fluoxetine is an antidepressant commonly prescribed not only to adults but also to children for the treatment of depression, obsessive-compulsive disorder, and neurodevelopmental disorders. The adverse effects of the long-term treatment reported in some patients, especially in younger individuals, call for a detailed investigation of molecular alterations induced by fluoxetine treatment. Two-year fluoxetine administration to juvenile macaques revealed effects on impulsivity, sleep, social interaction, and peripheral metabolites. Here, we built upon this work by assessing residual effects of fluoxetine administration on the expression of genes and abundance of lipids and polar metabolites in the prelimbic cortex of 10 treated and 11 control macaques representing two monoamine oxidase A (MAOA) genotypes. Analysis of 8871 mRNA transcripts, 3608 lipids, and 1829 polar metabolites revealed substantial alterations of the brain lipid content, including significant abundance changes of 106 lipid features, accompanied by subtle changes in gene expression. Lipid alterations in the drug-treated animals were most evident for polyunsaturated fatty acids (PUFAs). A decrease in PUFAs levels was observed in all quantified lipid classes excluding sphingolipids, which do not usually contain PUFAs, suggesting systemic changes in fatty acid metabolism. Furthermore, the residual effect of the drug on lipid abundances was more pronounced in macaques carrying the MAOA-L genotype, mirroring reported behavioral effects of the treatment. We speculate that a decrease in PUFAs may be associated with adverse effects in depressive patients and could potentially account for the variation in individual response to fluoxetine in young people.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
22
Issue :
15
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.f895fec8ff5b457cb67c95f9c71d2310
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms22158089