|
RESEARCH SUMMARY:
Opioid receptors are the targets of narcotics such as morphine and heroin. The long-range goal of our research is focused on how opioids affect brain development.
We are studying the mechanism of action of endogenous opioid peptides and pharmacological doses of opiates that occur in maternal drug abuse. Using primary, immortalized and transformed astrocytes as developmental model systems, we have discovered that opioid agonists modulate cell proliferation by a receptor-mediated mechanism. Opioid signaling pathways converge with those of growth factor signaling to regulate the ERK/MAP kinase phosphorylation cascade in this process. We found that G protein subunits, phosphatidylinositide turnover, calcium ion mobilization, protein kinase C, and calmodulin were key signaling elements in the opioid pathway. Acute opioids have proliferative actions, whereas chronic µ opioid agonists induce anti-proliferative effects. The latter results have possible implications for the psychological and physiological delays seen in offspring upon maternal opiate abuse (a contemporary problem of considerable proportion).
In adult brain, these same mechanisms may be responsible for opioid-induced neuroplasticity. It is now apparent that the adult CNS has a limited but detectable potential to generate new neurons and glia from neural progenitor cells. To develop neuronal and glial replacement strategies after brain damage due to disease or trauma, it is critical to identify extracellular signals that stimulate cell division and regulate the fate of neural progenitor cells. The propagation and maturation of neural progenitor cells are regulated by growth factors and in some cases opioids. Thus, we are characterizing the mechanism of opioid action in the maturation of stem cells to neurons and glia.
|
