Cyclic AMP regulates the rate of differentiation of oligodendrocytes without changing the lineage commitment of their progenitors.
Oligodendrocytes differentiate in primary cultures of rat brain cells on a specific schedule similar to that observed in vivo. We show that the pace of this developmental schedule is accelerated by the addition of the cyclic AMP analogs dibutyryl cAMP (dbcAMP) or 8-bromo cAMP. Dibutyryl cAMP also inhibits DNA synthesis in A2B5-positive oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells, consistent with the relationship between cessation of proliferation and onset of differentiation observed in vivo and in vitro. Treatment of cultures with dbcAMP has no effect on the proportion of O-2A progenitors that become oligodendrocytes rather than type 2 astrocytes and thus does not affect progenitor lineage decisions. Thus, cyclic AMP analogs accelerate the differentiation of cells apparently already determined to become oligodendrocytes.
Raible
D W
DW
David Mahoney Institute of Neurological Sciences, University of Pennsylvania, Philadelphia.
McMorris
F A
FA
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001769:Blood; D001921:Brain / Q000166:cytology / Q000254:growth & development; D003994:Bucladesine / Q000494:pharmacology; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D009457:Neuroglia / Q000166:cytology*; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D007328:Insulin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D004247:DNA; D000242:Cyclic AMP