Blocking of carnitine palmitoyl transferase 1 potently reduces stress-induced depression in rat highlighting a pivotal role of lipid metabolism

Scientific Reports
Anne Skøttrup MørkholtJohn Dirk Nieland

Abstract

Major depressive disorder is a complex and common mental disease, for which the pathology has not been elucidated. The purpose of this study is to provide knowledge about the importance of mitochondrial dysfunction, dysregulated lipid metabolism and inflammation. Mitochondrial carnitine palmitoyl transferase 1a (CPT1a) is a key molecule involved in lipid metabolism and mutations in CPT1a causing reduced function is hypothesized to have a protective role in the development of depression. Moreover, CPT1a is found to be upregulated in suicide patients with history of depression. Therefore, we hypothesized that inhibition of CPT1a activity can be developed as an innovative treatment strategy for depression. Stress exposure combined with different pharmacological treatment regimens; Etomoxir, CPT1 blocker, and Escitalopram, a favoured antidepressant drug, was applied in state-of-the-art chronic mild stress model. Etomoxir treatment induced statistical significant reduction of anhedonic behavior compared to vehicle treatment (p < 0.0001) and reversed depression-like phenotype in 90% of the rats (p = 0.0007), whereas Escitalopram only proved 57% efficacy. Moreover, Etomoxir revealed downregulation of interferon-γ, interleukin-17α and ...Continue Reading

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Citations

Sep 19, 2019·Scientific Reports·Anne Skøttrup MørkholtJohn Dirk Vestergaard Nieland
Nov 11, 2021·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Emrin HorgusluogluUNKNOWN Alzheimer Disease Metabolomics Consortium

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Methods Mentioned

BETA
flow cytometry

Software Mentioned

affymetrix
Northern TM
GeneExpress®
Gene

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