Related Experiment Videos
mu-Opioid receptor activation enhances DNA synthesis in immature oligodendrocytes
1Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington 40536-0084, USA. peknapp@pop.uky.edu
Abstract:
Opioids disrupt nervous system development by inhibiting the proliferation of neuronal and glial progenitors. These studies explored the hypothesis that mu opioid receptors are expressed by immature oligodendrocytes (OLs) and are functionally related to growth. Antibodies identifying the cloned mu opioid receptor demonstrated that cultured OLs expressed mu opioid receptor immunoreactivity very early during development. Cultures were treated with the selective mu opioid receptor agonist H-Tyr-Pro-Phe (N-Me)-D-Pro-NH2 (PL017; 1 microM), or PL017 (1 microM) plus the antagonist naloxone (3 microM). Opioid-dependent changes in DNA synthesis were assessed by determining the proportion of bromodeoxyuridine (BrdU)-labeled O4-immunoreactive OLs. Treatment with PL017 caused a 311% increase in the proportion of O4-immunoreactive OLs incorporating BrdU compared to untreated controls, and these effects were prevented by co-administering naloxone. These preliminary results indicate that (i) immature OLs express mu opioid receptors and that (ii) the activation of this receptor type is functionally coupled to DNA synthesis and the cell division cycle. The expression of opioid receptors by OLs suggests that the endogenous opioid system is widely distributed among glial types.
Insights
Opioid receptors are present on developing oligodendrocytes (OLs), influencing their growth. Activating these receptors promotes OL proliferation, suggesting a role for the endogenous opioid system in nervous system development.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Opioids negatively impact nervous system development by hindering progenitor cell proliferation.
- Immature oligodendrocytes (OLs) are crucial glial cells for myelin formation during development.
Purpose of the Study:
- To investigate the presence and function of mu opioid receptors on immature OLs.
- To determine if mu opioid receptor activation affects OL proliferation and DNA synthesis.
Main Methods:
- Cultured immature OLs were analyzed for mu opioid receptor expression using specific antibodies.
- Cells were treated with a selective mu opioid receptor agonist (PL017) and antagonist (naloxone).
- DNA synthesis was measured by bromodeoxyuridine (BrdU) incorporation in O4-immunoreactive OLs.
Main Results:
- Immature OLs express mu opioid receptor immunoreactivity early in development.
- Treatment with the mu opioid receptor agonist PL017 significantly increased BrdU incorporation by 311% in OLs.
- The agonist-induced increase in proliferation was blocked by the antagonist naloxone.
Conclusions:
- Immature oligodendrocytes express functional mu opioid receptors.
- Activation of mu opioid receptors stimulates DNA synthesis and cell division in OLs.
- This suggests the endogenous opioid system plays a role in glial development.