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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
Morphine induces apoptosis of human microglia and neurons
Shuxian Hu1, Wen S Sheng, James R Lokensgard
1Neuroimmunology Laboratory, Minneapolis Medical Research Foundation, Minneapolis, MN 55404, USA.
Abstract:
Apoptosis plays a critical role in normal brain development and in a number of neurodegenerative diseases. Recently, opiates have been shown to promote apoptotic death of cells of the immune and nervous systems. In this study, we investigated the effect of morphine on apoptosis of primary human fetal microglial cell, astrocyte and neuronal cell cultures. Exposure of microglia and neurons to 10(-6) M morphine potently induced apoptosis of these brain cells (approximately fourfold increase above untreated control cells). In contrast to microglia and neurons, astrocytes were completely resistant to morphine-induced apoptosis. Concentration-response and time-course studies indicated that neurons were more sensitive than microglia to morphine's effect on apoptosis. Naloxone blocked morphine-induced apoptosis suggesting involvement of an opiate receptor mechanism. Potent inhibition (>70%) of apoptosis by an inhibitor of caspase-3 as well as co-localization of active caspase-3 and DNA fragmentation in microglia or neurons treated with morphine indicated that caspase-3 is involved in the execution phase of morphine-induced apoptosis. The results of these in vitro studies have implications regarding the potential effect of opiates on fetal brain development and on the course of certain neurodegenerative diseases.
Insights
Morphine induces apoptosis in human fetal microglia and neurons, but not astrocytes. This opiate-induced cell death involves caspase-3 and suggests potential risks to fetal brain development.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Apoptosis is crucial for brain development and neurodegenerative diseases.
- Opiates are known to induce cell death in immune and nervous system cells.
Purpose of the Study:
- To investigate the effect of morphine on apoptosis in primary human fetal microglial, astrocyte, and neuronal cell cultures.
- To elucidate the mechanisms underlying morphine-induced apoptosis.
Main Methods:
- Primary human fetal microglial, astrocyte, and neuronal cell cultures were exposed to morphine.
- Apoptosis was assessed, and involvement of opiate receptors and caspase-3 was investigated using naloxone and a caspase-3 inhibitor.
- Confocal microscopy was used to visualize active caspase-3 and DNA fragmentation.
Main Results:
- Morphine (10(-6) M) significantly increased apoptosis in microglia and neurons (approx. fourfold increase).
- Astrocytes were resistant to morphine-induced apoptosis.
- Neurons were more sensitive to morphine's apoptotic effects than microglia.
- Naloxone blocked morphine-induced apoptosis, indicating opiate receptor involvement.
- Caspase-3 inhibition and co-localization of active caspase-3 with DNA fragmentation confirmed caspase-3's role in the execution phase.
Conclusions:
- Morphine induces apoptosis in human fetal microglia and neurons via an opiate receptor-mediated pathway involving caspase-3.
- Astrocytes are resistant to morphine-induced apoptosis.
- These findings highlight potential risks of opiate exposure to fetal brain development and neurodegenerative disease progression.
