Reversal of opiate-induced apoptosis by human recombinant growth hormone in murine foetus primary hippocampal neuronal cell cultures.
Previous studies have shown that chronic opiates may inhibit cell growth and trigger apoptosis leading to impaired cognitive capabilities in both humans and other mammals. In contrast, growth hormone (GH) has been demonstrated to stimulate cell growth and counteract apoptosis. GH has also been shown to improve learning and memory in both human and rodents. In this work, we demonstrate that GH may reverse opiate-induced apoptosis in cells derived from prenatal mouse hippocampus. Primary hippocampal cell cultures derived from 16-day-old fetal mouse neurons were treated with morphine for 7 days during growth in the absence or presence of recombinant human GH (rhGH). The release of lactate dehydrogenase (LDH) into the culture media and the level of cleaved caspase-3 were measured. Results indicate that morphine (15 microM) decreased the cell content in a concentration-dependent manner and increased LDH release and caspase-3 activity. Thus, fetal mouse neurons treated with morphine showed less viability compared with controls. Interestingly, the addition of rhGH (1 microM) counteracted the morphine-induced effect on the cell density. Furthermore, the hormone attenuated the effects on LHD release and caspase-3 activity elicited by morphine. These results suggest that the hormone is capable of preventing or even repairing morphine-induced damage to hippocampal cells.
Svensson
Anne-Lie
AL
Department of Pharmaceutical Biosciences, Uppsala University, P. O. Box 591, S-751 24 Uppsala, Sweden. anne-lie.svensson@farmbio.uu.se
Bucht
Nora
N
Hallberg
Mathias
M
Nyberg
Fred
F
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology* / Q000196:embryology* / Q000473:pathology; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009020:Morphine / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D018847:Opioid Peptides / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000737:chemistry
D018847:Opioid Peptides; D011994:Recombinant Proteins; D009020:Morphine; D013006:Growth Hormone; D053148:Caspase 3