Reversal of opiate-induced apoptosis by human recombinant growth hormone in murine foetus primary hippocampal neuronal cell cultures

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 105; no. 20; pp. 7304 - 7308
• Main Authors: Svensson, Anne-Lie, Bucht, Nora, Hallberg, Mathias, Nyberg, Fred
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 20.05.2008; National Acad Sciences
• Series: From the Cover
• Subjects: Animals; Apoptosis; Biological Sciences; Brain; Caspase 3 - metabolism; caspase-3; Cell culture; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; FARMACI; Growth Hormone - metabolism; Growth hormones; Hippocampus; Hippocampus - cytology; Hippocampus - embryology; Hippocampus - pathology; Hormones; Humans; lactate dehydrogenase; Mice; Models, Biological; Morphine; Morphine - pharmacology; Neurogenesis; Neurons; Neurons - metabolism; Neurosciences; Opiates; Opioid Peptides - pharmacology; PHARMACY; Proteases; Rats; Recombinant Proteins - chemistry; Studies
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0802531105

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 μM) 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 μM) 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.