@entity1919 -elevating agents are highly effective in preventing the loss of dopaminergic neurons that occurs spontaneously in neuronal-glial mesencephalic cultures. We demonstrate here that @entity268 causes a concomitant decline in the number of dividing non-neuronal cells, suggesting that inhibition of proliferation contributes to neuroprotection. Consistent with this hypothesis, a transient treatment with the antimitotic @entity2592 , at concentrations that induce long-term repression of glial cell proliferation, mimicked the neuroprotective action of @entity268 and also obviated the need for the @entity1921 . Treatment with @entity268 -elevating agents reduced the population of OX-42-positive microglial cells and the number of immature astrocytes expressing vimentin and low levels of the astrocytic marker glial fibrillary acidic protein. The effect on the immature astrocytes, however, seemed essential for neuroprotection. @entity2057 and @entity1778 inhibitory factor, which stimulate astrocyte differentiation without reducing cell proliferation, failed to reproduce the protective effects of the cyclic @entity377 . @entity1919 did not operate by counteracting the action of the astrocyte mitogen epidermal growth factor or by reducing activation of the mitogen-activated protein kinase signaling pathway. The neuroprotective and antiproliferative actions of @entity268 , however, were closely mimicked by @entity38501 and @entity9363 , potent inhibitors of the cyclin-dependent kinase @entity10610 that are structurally related to @entity268 . Measurement of @entity10610 activity confirmed that neuroprotection was closely correlated with inhibition of this kinase by @entity268 . In summary, neuroprotection of mesencephalic dopaminergic neurons by @entity268 most probably requires the repression of presumptive astrocytes through inhibition of @entity10610 .

Prevention of dopaminergic neuronal death by XXXX in mixed neuronal/glial mesencephalic cultures requires the repression of presumptive astrocytes.

@entity268 :: ('CHEBI:17489', 'Chemical') :: ['cAMP'] @entity10610 :: ('983', 'Gene') :: ['CDK1'] @entity377 :: ('CHEBI:36976', 'Chemical') :: ['nucleotide'] @entity1921 :: ('CHEBI:23447', 'Chemical') :: ['cyclic nucleotide'] @entity2592 :: ('MESH:D003561', 'Chemical') :: ['cytosine arabinoside'] @entity1778 :: ('MESH:D007938', 'Disease') :: ['leukemia'] @entity1919 :: ('MESH:D000242', 'Chemical') :: ['Cyclic AMP'] @entity9363 :: ('MESH:C104586', 'Chemical') :: ['roscovitine'] @entity2057 :: ('MESH:D009133', 'Disease') :: ['Ciliary neurotrophic factor'] @entity38501 :: ('MESH:C090046', 'Chemical') :: ['olomoucine']
@entity1919 :: (MESH:D000242,Chemical) :: ['cyclic AMP']
