OLIGODENDROGLIAL SIGNAL-TRANSDUCTION SYSTEMS ARE DEVELOPMENTALLY-REGULATED

Studies from several laboratories indicate that oligodendroglia exhibi t signal transduction systems that can be activated by classical neuro transmitters. Previous studies from this laboratory indicate that olig odendroglia express neuroligand receptors linked to the regulation of Ca-i(2+). Experiments presented in this article were designed to deter mine if developmental processes that influence the ability of oligoden droglia to respond to neuroligands with an increase in Ca-i(2+) procee d either in vitro or in vivo. Findings support the view that developme ntal processes markedly affected the sensitivity of these cells to bot h purinergic and cholinergic receptor agonists, whereas their responsi veness to either histamine or bradykinin appeared relatively stable ov er time. Approximately 90 and 75% of oligodendroglia responded to ATP or carbachol, respectively, after 4 days in vitro, whereas <10% of the se cells responded to either of these neuroligands after 8 days in vit ro. The decrease in the percentage of oligodendroglia responding to AT P, but not carbachol, could be prevented by including dibutyryl cyclic AMP in the culture medium during the final 4 days in vitro. However, once the loss in responsiveness to ATP had occurred, it could not be r eversed by exposure to dibutyryl cyclic AMP. Developmental changes in the ATP sensitivity of oligodendroglia occurred in cells expressing ga lactocerebroside and myelin basic protein. The neuroligand sensitivity of oligodendroglia isolated from either neonatal, 2-, 3-, or 5-week-o ld spinal cord was examined to determine if developmental changes in o ligodendroglial Ca2+ regulation occurred in vivo The results of these experiments indicate that the percentage of oligodendroglia responding to either ATP or carbachol markedly decreased as a function of the ag e of the animal used to prepare the cultures; this was not the case fo r the stimulation of Ca-i(2+) by histamine. The decreased sensitivity of oligodendroglia isolated from older animals could not be reversed t hrough the addition of dibutyryl cyclic AMP. Overall, the results of t hese experiments indicate that developmental processes selectively inf luence the sensitivity of oligodendroglia to specific neuroligands and suggest that oligodendroglial processes unrelated to myelin formation may be regulated by neuroligands in vivo.