Morphine sulfate concomitantly decreases neuronal differentiation and opioid receptor expression in mouse embryonic stem cells

Toxicology Letters
Sanjay L DholakiyaFrank A Barile

Abstract

Opioids have been shown to affect prenatal and postnatal neural development in mammals. The present study investigates the impact of morphine sulfate (MS) treatment on neuronal differentiation as well as μ-opioid receptor (MOR) expression in mouse embryonic stem (mES) cells. Stem cells were manipulated in culture to differentiate in 3 sequential stages: Stage 1, cell transformation to embryoid bodies (EB); Stage 2, EB cell differentiation to neural progenitor (NP) cells; and, Stage 3, NP cell differentiation to neurons/astrocytes co-cultured cells. Using RT-PCR and flow cytometry analyses, cell types were confirmed by monitoring expression of Oct4, nestin, microtubule-associated protein 2 (mtap-2), and glial fibrillary acidic protein (GFAP) as cell-specific markers for stem cells, NP cells, neurons, and astrocytes, respectively. Similarly, gene expression for MOR, κ-opioid receptor (KOR), and δ-opioid receptor (DOR) was confirmed in each cell type. In order to investigate the effects of MS on differentiation, cells were treated with MS (1, 10, 100μM) at either early (Stage 1) or late (Stage 3) stage of cellular differentiation. At Stage 1 exposure, MOR gene expression and neuroectoderm specific marker expression of nestin were ...Continue Reading

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Citations

Oct 27, 2018·The Journal of Pharmacology and Experimental Therapeutics·Anne Marte Sjursen KvelloInger Lise Bogen
Dec 12, 2018·Journal of Cellular Physiology·Romana ŠínováLukáš Kubala
Dec 7, 2018·Nature Reviews. Neuroscience·Cherkaouia KibalyPing-Yee Law
Jan 6, 2021·International Journal of Molecular Sciences·Jana BrejchovaPetr Svoboda

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