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Updated: Feb 4, 2026
Preparation and In Vitro Characterization of Magnetized miR-modified Endothelial Cells
Published on: May 2, 2017
Opioid and Notch signaling pathways are reciprocally regulated through miR- 29a and miR-212 expression
Adrian Garcia-Concejo1, Ada Jimenez-Gonzalez1, Raquel E Rodriguez2
1Institute of Neurosciences of Castilla y Leon (INCyL), C/Pintor Fernando Gallego, 1, 37007 Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL), Hospital Universitario de Salamanca, Edificio Virgen de la Vega. Décima Planta, P° de San Vicente 58-182, 37007 Salamanca, Spain.
Background:
The abuse of opioids, such as morphine and phentanyl or other drugs as heroin is a social and health problem that affects an increasing number of people each year. The activation of the mu opioid receptor triggers several molecular changes that alter the expression of diverse genes, including miRNAs. The dysregulation of these molecules could explain some of the developmental alterations that are induced after drug intake. In addition, the Notch signaling cascade has also been related to alterations on these processes.
Methods:
Zebrafish embryos and SH-SY5Y cells were used to assess the effects of opioid and Notch signaling on the expression on miR-29a and miR-212/132 by qPCR and ChIP-qPCR. Notch1 expression was analyzed using in situ hybridization on 24 hpf zebrafish embryos. In addition, OPRM1 and NICD levels were measured using western blot on the cultured cells to determine the cross-talk between the two pathways.
Results:
We have observed changes in the levels of miR-212/132 after administrating DAPT to zebrafish embryos indicating that this pathway could be regulating mu opioid receptor expression. In addition, the ISH experiment showed changes in Notch1 expression after morphine and DAPT administration. Moreover, morphine affects the expression of miR-29a through NF-κB, therefore controlling the cleavage and activation of Notch through ADAM12 expression.
Conclusions:
This study shows that these two pathways are closely related, and could explain the alterations triggered in the early stages of the development of addiction.
General Significance:
Opioid and Notch pathway are reciprocally regulated by the miRNAs 212/132 and 29a.
Insights
Opioid and Notch signaling pathways are interconnected and regulated by specific microRNAs (miRNAs). This interaction may explain developmental changes associated with early addiction.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Opioid abuse is a significant health issue with molecular consequences.
- Opioid receptor activation alters gene expression, including microRNAs (miRNAs).
- Notch signaling is implicated in developmental processes and may interact with opioid pathways.
Purpose of the Study:
- To investigate the interplay between opioid and Notch signaling pathways.
- To determine the role of specific miRNAs in regulating these pathways.
- To understand molecular mechanisms underlying developmental alterations in addiction.
Main Methods:
- Utilized zebrafish embryos and SH-SY5Y cells for experiments.
- Assessed miRNA expression (miR-29a, miR-212/132) using qPCR and ChIP-qPCR.
- Analyzed Notch1 expression via in situ hybridization and western blot for OPRM1 and NICD levels.
Main Results:
- Administration of DAPT altered miR-212/132 levels, suggesting Notch pathway regulation of mu opioid receptor.
- Morphine and DAPT affected Notch1 expression in zebrafish embryos.
- Morphine influenced miR-29a expression via NF-κB, impacting ADAM12 and Notch activation.
Conclusions:
- The opioid and Notch signaling pathways are closely related.
- MiRNAs (miR-212/132 and miR-29a) reciprocally regulate these pathways.
- This cross-talk may explain developmental alterations in early addiction stages.
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