Mu‐ and delta‐opioid receptor antagonists decrease proliferation and increase neurogenesis in cultures of rat adult hippocampal progenitors

European Journal of Neuroscience - Tập 17 Số 6 - Trang 1159-1172 - 2003
Anders I. Persson1, Thorleif Thorlin1, Cecilia Bull1, Parisa Zarnegar2, Rolf Ekman1, Lars Terenius2, Peter S. Eriksson1
1Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden
2Institute of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden

Tóm tắt

AbstractOpioids have previously been shown to affect proliferation and differentiation in various neural cell types. In the present study, cultured rat adult hippocampal progenitors (AHPs) were shown to release β‐endorphin. Membrane preparations of AHPs were found to bind [125I]β‐endorphin, and immunoreactivity for mu‐ and delta‐opioid receptors (MORs and DORs), but not for kappa‐opioid receptors (KORs), was found on cells in culture. Both DNA content and [3H]thymidine incorporation were reduced after a 48‐h incubation with 100 µm naloxone, 10 µm naltrindole or 10 µmβ‐funaltrexamine, but not nor‐binaltorphimine, suggesting proliferative actions of endogenous opioids against MORs and DORs on AHPs. Furthermore, analysis of gene and protein expression after incubation with MOR and DOR antagonists for 48 h using RT‐PCR and Western blotting suggested decreased signalling through the mitogen‐activated protein kinase (MAPK) pathway and lowered levels of genes and proteins that are important in cell cycling. Cultures were incubated with naloxone (10 or 100 µm) for 10 days to study the effects on differentiation. This resulted in an approximately threefold increase in neurogenesis, a threefold decrease in astrogliogenesis and a 50% decrease in oligodendrogenesis. In conclusion, this study suggests that reduced signalling through MORs and DORs decreases proliferation in rat AHPs, increases the number of in vitro‐generated neurons and reduces the number of astrocytes and oligodendrocytes in culture.

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Tài liệu tham khảo

10.1006/mcne.2000.0947

10.1159/000054592

10.1523/JNEUROSCI.15-05-03328.1995

10.1016/S0361-9230(96)00298-5

10.1074/jbc.M101535200

10.1046/j.1471-4159.1998.70051819.x

10.1523/JNEUROSCI.21-19-07598.2001

10.1021/ac010777q

10.1016/S0306-4522(99)00030-5

10.1016/0003-2697(87)90021-2

10.1002/cne.903450104

10.1073/pnas.120552597

10.1073/pnas.94.23.12258

10.1046/j.1471-4159.1996.67031309.x

10.1126/science.287.5457.1433

10.1073/pnas.92.25.11879

10.1016/S0896-6273(01)00209-4

10.1097/00000542-199711000-00016

10.1002/glia.440090209

10.1046/j.1460-9568.2000.01015.x

10.1016/0006-8993(87)91509-5

10.1002/cne.902810103

10.1037/0735-7044.116.1.160

10.1016/S0168-0102(96)01141-8

10.1002/(SICI)1098-2795(200006)56:2<113::AID-MRD1>3.0.CO;2-Q

10.1002/(SICI)1098-1136(199802)22:2<189::AID-GLIA10>3.0.CO;2-U

10.1016/0165-3806(87)90081-2

10.1016/S0028-3908(99)00243-9

10.1523/JNEUROSCI.17-15-05820.1997

10.1016/S0006-8993(98)00806-3

Law P.Y., 1995, Properties of delta opioid receptor in neuroblastoma NS20Y: receptor activation and neuroblastoma proliferation, J. Pharmacol. Exp. Ther., 272, 322

10.1016/S0165-3806(00)00064-X

10.1016/S0014-5793(96)01126-X

10.1016/0092-8674(93)90666-E

10.1016/0166-2236(95)93946-U

10.1016/0006-8993(95)00928-J

Mansour A., 1987, Autoradiographic differentiation of mu, delta, and kappa opioid receptors in the rat forebrain and midbrain, J. Neurosci., 7, 2445

10.1002/cne.902550403

10.1002/cne.902080209

10.1006/mcne.1996.0595

10.1046/j.1460-9568.1999.00680.x

10.1016/0006-8993(89)90515-5

10.1016/0361-9230(93)90078-P

10.1523/JNEUROSCI.20-23-08727.2000

10.1097/00000542-200110000-00030

10.1152/ajpcell.1993.264.3.C632

Soliven B., 1995, Arachidonic acid inhibits potassium conductances in cultured rat oligodendrocytes, Am. J. Physiol., 269, C341, 10.1152/ajpcell.1995.269.2.C341

10.1038/nn844

10.1016/S0168-0102(00)00226-1

10.1016/0165-3806(91)90149-D

10.1002/glia.1097

10.1002/(SICI)1097-4695(199901)38:1<65::AID-NEU5>3.0.CO;2-Q

10.1002/(SICI)1098-1136(199711)21:3<277::AID-GLIA3>3.0.CO;2-2

10.1016/S0028-3908(98)00026-4

10.1016/0167-0115(86)90018-2

10.1016/0165-3806(86)90025-8

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European Journal of Neuroscience

Tập 17 Số 6

1159-1172

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