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Brain Res Bull. 2021 Jun;171:126-134. doi: 10.1016/j.brainresbull.2021.03.009. Epub 2021 Mar 16.

The effects of morphine, methadone, and fentanyl on mitochondria: A live cell imaging study.

Brain research bulletin

Erik Nylander, Sofia Zelleroth, Fred Nyberg, Alfhild Grönbladh, Mathias Hallberg

Affiliations

  1. The Beijer Laboratory, Dept. of Pharmaceutical Biosciences, Uppsala University, SE-751 24, Uppsala, Sweden.
  2. The Beijer Laboratory, Dept. of Pharmaceutical Biosciences, Uppsala University, SE-751 24, Uppsala, Sweden. Electronic address: [email protected].

PMID: 33741459 DOI: 10.1016/j.brainresbull.2021.03.009

Abstract

The important role of mitochondria in maintaining normal brain cell function has been demonstrated in several neurodegenerative diseases where mitochondrial dysfunction is a prominent feature. Accumulating evidence indicates that opioids may induce neuronal cell death and inhibit neurogenesis, two factors that are dependent on normal mitochondrial function. The aim of the present study was to examine the effects of morphine, methadone, and fentanyl on MitoTracker-stained mitochondria. Cells from the neuroblastoma/glioma hybrid cell-line NG108-15 were seeded on 96-well cell culture plates and treated with MitoTracker for 30 min prior to opioid treatment. Morphine, methadone, and fentanyl were added at various concentrations and images of mitochondria were acquired every 30 min for four hours using a high-content imaging device. The parameters total mitochondrial area, mitochondrial network, as well as the number and mean area of mitochondrial objects were analyzed using automated image analysis. Methadone and fentanyl, but not morphine, decreased the mitochondrial network, the number of mitochondrial objects, and increased the mean area of mitochondrial objects. Both methadone and fentanyl altered mitochondrial morphology with no effects seen from morphine treatment. These data suggest that methadone and fentanyl impact mitochondrial morphology negatively, which may be associated with neuronal cell death.

Copyright © 2021. Published by Elsevier Inc.

Keywords: Fentanyl; In vitro; Live cell imaging; Methadone; Morphine; Opioids

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