Acute in utero morphine exposure slows G2/M phase transition in radial glial and basal progenitor cells in the dorsal telencephalon of the E15.5 embryonic mouse.
The antiproliferative effects of opiate exposure on neurogenesis in vitro have been well documented, but the effects of opiates on brain development in vivo are less well understood. We have recently shown that mu opioid receptors are expressed on radial glia of the lateral ventricle, the neuronal and glial progenitor cells of the developing cortex. In the present study we show that in vivo morphine treatment of the E15.5 mouse increases the length of the G(2)/M phase of the radial glial cell cycle in the dorsal telencephalon, as well as slows interkinetic nuclear migration of radial glial nuclei from the basal ventricular zone to the apical surface. A prolonged G(2)/M phase was also observed in basal progenitor cells. Although morphine exposure altered the duration of the cell cycle for progenitor cells in the embryonic telencephalon, it did not affect whether the progenitors remained proliferative and re-entered the S phase, or whether they exited the cell cycle and became quiescent. In addition, morphine treatment did not change the proportion of basal to apical mitoses. These findings indicate that opioid signalling plays a role in cell cycle progression of both radial glia and basal progenitor cells in vivo in the developing cerebral cortex.
Sargeant
Tim J
TJ
School of Biological Sciences, Wellington 6140, New Zealand.
Day
Darren J
DJ
Miller
John H
JH
Steel
Ryan W J
RW
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D005260:Female; D016195:G2 Phase / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013687:Telencephalon / Q000166:cytology / Q000187:drug effects / Q000196:embryology
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D009020:Morphine