Endogenous opioid systems and the growth of oligodendrocyte progenitors: paradoxical increases in oligodendrogenesis as an indirect mechanism of opioid action.
Endogenous opioids inhibit nervous system development by inhibiting the proliferation of certain neuronal and glial progenitors. To determine whether opioids affect the growth of preoligodendrocytes, the effects of the endogenous opioid [Met5]-enkephalin were examined in preoligodendrocytes in primary mixed-glial and preoligodendrocyte-enriched (> 98% pure) cultures. Proliferating preoligodendrocytes in mixed-glial or preoligodendrocyte-enriched cultures were continuously treated for a total of 40 h with either basal growth media (controls), 1 microM [Met5]-enkephalin, 1 microM [Met5]-enkephalin plus the opioid antagonist naloxone (3 microM), or naloxone alone (3 microM), and incubated in [3H]-thymidine (0.2 microCi/ml/4-6 h) after 34-36 h of opioid exposure. Opioid-dependent changes in DNA synthesis were assessed autoradiographically in O4-immunoreactive oligodendrocyte progenitors. Naloxone alone significantly decreased the rate of DNA synthesis and number of O4-immunoreactive preoligodendrocytes in mixed-glial cultures. However, naloxone and/or [Met5]-enkephalin did not affect DNA synthesis or the number of O4-immunoreactive preoligodendrocytes in cultures enriched in preoligodendrocytes. The results suggest that astrocytes, or perhaps another cell type, play a permissive role in opioid-dependent alterations in preoligodendrocyte proliferation. Endogenous opioids affect the genesis of neural cells by both direct and indirect mechanisms.
Hauser
K F
KF
Department of Anatomy and Neurobiology, University of Kentucky School of Medicine, Lexington 40536-0084.
Gurwell
J A
JA
Bhat
N R
NR
D000818:Animals; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D004744:Enkephalin, Methionine / Q000502:physiology*; D009270:Naloxone / Q000008:administration & dosage; D009836:Oligodendroglia / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology*
D009270:Naloxone; D004744:Enkephalin, Methionine; D004247:DNA