uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The effects of morphine, methadone, and fentanyl on mitochondrial morphology: a live cell imaging study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Show others and affiliations
(English)Manuscript (preprint) (Other academic)
Abstract [en]

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 mitochondrial morphology. 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 morphological parameters total mitochondrial area, mitochondrial network, number of mitochondrial objects, and the 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 disrupt mitochondrial morphology, which may contribute to neuronal cell death.

Keywords [en]
Cell culture, Fentanyl, Live cell imaging, Methadone, Mitochondria, Morphine, Morphology, NG108-15, Opioids, Time-lapse
National Category
Cell and Molecular Biology
Research subject
Pharmaceutical Science
Identifiers
URN: urn:nbn:se:uu:diva-393936OAI: oai:DiVA.org:uu-393936DiVA, id: diva2:1355573
Funder
Swedish Research Council, 9459The Swedish Brain FoundationAvailable from: 2019-09-30 Created: 2019-09-30 Last updated: 2019-10-04
In thesis
1. The effects of growth hormone on opioid-induced toxicity in vitro
Open this publication in new window or tab >>The effects of growth hormone on opioid-induced toxicity in vitro
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

There is an ongoing opioid crisis in the United States that is portrayed by a large number of opioid-related deaths. Many of these cases involve commonly used prescription opioids, such as morphine, oxycodone, fentanyl, and methadone. This is concerning and highlights the problems associated with long-term opioid treatment. In addition to opioid-related deaths, long-term opioid use may impact higher brain functions, such as cognitive function. The cause of cognitive decline following opioid treatment may be associated with increased neuronal cell death, inhibited neurogenesis, and altered volumes of specific brain regions important for cognition. Growth hormone (GH), a pituitary hormone regulated by the hypothalamic somatotropic axis, may counteract several of these effects. The hormone, alongside with its mediator insulin-like growth factor-1 (IGF-1), is associated with pro-cognitive effects and display promising neuroprotective actions in the CNS. The main aim for this thesis was to examine the impact of opioids on cell viability and the potentially protective, restorative, and effects linked to pro-cognitive properties of GH in mixed neuronal cell cultures and cell lines. The results clearly display that specific opioids, such as methadone, decrease cell viability, possibly via negative effects on mitochondrial morphology. GH treatment alleviated the negative effects of methadone in cortical cell cultures as well as successfully restored mitochondrial and membrane integrity past injury. Moreover, GH treatment to primary hippocampal cell cultures increased the number of dendritic spines, which are linked to higher cognitive functions, indicating that the hormone act as a cognitive enhancer in the CNS. In conclusion, this thesis provides further evidence that opioids negatively impact cell viability, an effect that may underlie reduced cognitive function as seen in several patients consuming opioids-long term. GH was able to counteract these effects and also able to restore damaged cellular functions. This thesis further confirms the essential role of GH in acting as a cognitive enhancer in the CNS, highlighting the potential role of GH as a treatment for cognitive dysfunctions.    

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 60
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 279
Keywords
Growth hormone, opioids, methadone, morphine, ketobemidone, fentanyl, oxycodone, hydromorphone, insulin-like growth factor, cell viability, NG108-15, SH-SY5Y, hippocampus, cortex
National Category
Cell and Molecular Biology Pharmaceutical Sciences Pharmacology and Toxicology
Research subject
Pharmaceutical Science
Identifiers
urn:nbn:se:uu:diva-393940 (URN)978-91-513-0765-7 (ISBN)
Public defence
2019-11-22, B21, Biomedicinskt centrum (BMC), Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2019-10-30 Created: 2019-10-04 Last updated: 2019-11-12

Open Access in DiVA

No full text in DiVA

Authority records BETA

Nylander, ErikZelleroth, SofiaNyberg, FredGröndbladh, AlfhildHallberg, Mathias

Search in DiVA

By author/editor
Nylander, ErikZelleroth, SofiaNyberg, FredGröndbladh, AlfhildHallberg, Mathias
By organisation
Department of Pharmaceutical Biosciences
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 87 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf