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Article

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

1
V. Zelman Center for Neurobiology and Brain Restoration, Skolkovo Institute of Science and Technology, 121205 Moscow, Russia
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Faculty of Bioengineering and Bioinformatics, Moscow State University, 119234 Moscow, Russia
3
Proteomics and Biomarkers, Max Planck Institute of Psychiatry, 80804 Munich, Germany
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Institute of Anatomy and Cell Biology, Ludwig-Maximilians University, 80336 Munich, Germany
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Center of Life Sciences, Skolkovo Institute of Science and Technology, 121205 Moscow, Russia
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California National Primate Research Center, University of California, Davis, CA 95616, USA
*
Authors to whom correspondence should be addressed.
Contributed equally.
Present address: Department of Biomedicine, Aarhus University, Ole Worms Allé 3, 8000 Aarhus C, Denmark.
Academic Editor: Akiyoshi Saitoh
Int. J. Mol. Sci. 2021, 22(15), 8089; https://doi.org/10.3390/ijms22158089
Received: 22 June 2021 / Revised: 13 July 2021 / Accepted: 16 July 2021 / Published: 28 July 2021
(This article belongs to the Section Molecular Pharmacology)
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. View Full-Text
Keywords: fluoxetine; antidepressant; lipidomics; lipids; PUFA; transcriptomics; depression; macaca mulatta fluoxetine; antidepressant; lipidomics; lipids; PUFA; transcriptomics; depression; macaca mulatta
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MDPI and ACS Style

Tkachev, A.; Stekolshchikova, E.; Bobrovskiy, D.M.; Anikanov, N.; Ogurtsova, P.; Park, D.I.; Horn, A.K.E.; Petrova, D.; Khrameeva, E.; Golub, M.S.; Turck, C.W.; Khaitovich, P. Long-Term Fluoxetine Administration Causes Substantial Lipidome Alteration of the Juvenile Macaque Brain. Int. J. Mol. Sci. 2021, 22, 8089. https://doi.org/10.3390/ijms22158089

AMA Style

Tkachev A, Stekolshchikova E, Bobrovskiy DM, Anikanov N, Ogurtsova P, Park DI, Horn AKE, Petrova D, Khrameeva E, Golub MS, Turck CW, Khaitovich P. Long-Term Fluoxetine Administration Causes Substantial Lipidome Alteration of the Juvenile Macaque Brain. International Journal of Molecular Sciences. 2021; 22(15):8089. https://doi.org/10.3390/ijms22158089

Chicago/Turabian Style

Tkachev, Anna, Elena Stekolshchikova, Daniil M. Bobrovskiy, Nickolay Anikanov, Polina Ogurtsova, Dong I. Park, Anja K.E. Horn, Daria Petrova, Ekaterina Khrameeva, Mari S. Golub, Christoph W. Turck, and Philipp Khaitovich. 2021. "Long-Term Fluoxetine Administration Causes Substantial Lipidome Alteration of the Juvenile Macaque Brain" International Journal of Molecular Sciences 22, no. 15: 8089. https://doi.org/10.3390/ijms22158089

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