RESUMO
Ethanol consumption typically begins during adolescence and is associated with age-dependent responses and maladaptive neuronal consequences. Our previous work established the role of a putative signaling cascade involving cytoplasmic phospholipase A2 (cPLA2), arachidonic acid (AA) and novel protein kinase C isoforms in adolescent hypnotic sensitivity. The current study aimed to further delineate this pathway by ascertaining the cellular specificity as well as the upstream activators of cPLA2 using an immature cultured cortical preparation. A threefold increase in cPLA2 was detected within 2 min of 100 mM ethanol exposure as measured by phosphorylation of serine 505 (Ser505). Increases in cPLA2 activity were further observed to be primarily confined to neuronal cells. Increases in the number of neurons co-expressing cPLA2 Ser505 phosphorylation were prevented by preincubation with an ERK1/2 inhibitor, but not P38 MAPK inhibition. Finally, conditioned media studies were used to determine whether glial cells were involved in the ethanol-induced neuronal cPLA2 activity. Rapid increases in neuronal cPLA2 activity appears to be initiated through ethanol stimulated microglial, but not astrocytic releasable factors. Taken together, these data extend the proposed signaling cascade involved in developmental ethanol responding.
