Cultured PC12 CellsA Model for Neuronal Function, Differentiation, and Survival

Adverse Neurodevelopmental Effects of Dexamethasone Modeled in PC12 Cells: Identifying the Critical Stages and Concentration Thresholds for the Targeting of Cell Acquisition, Differentiation and Viability

“…These considerations become more important with the rise in activity seen as differentiating cells specialize into the two different phenotypes. As expected (Teng and Greene, 1994), NGF-induced differentiation produced a large increment in both ChAT and TH activities, whether assessed on a per cell basis or relative to total protein. However, whereas DEX increased TH activity, it decreased ChAT, again at concentrations orders of magnitude below those required for clinical utility.…”

“…Primary neurons do not maintain cell division in culture and do not provide a uniform population either in terms of cell types or differentiation state. In the current study, we utilized rat pheochromocytoma PC12 cells, a model for evaluating neuronal cell replication and differentiation (Teng and Greene, 1994). In the presence of nerve growth factor (NGF), the cells gradually exit the mitotic cycle and begin to differentiate, developing axonal projections, electrical excitability, and the characteristics of two distinct phenotypes, cholinergic, and catecholaminergic neurons (Fujita et al, 1989;Song et al, 1998;Teng and Greene, 1994).…”

“…In the current study, we utilized rat pheochromocytoma PC12 cells, a model for evaluating neuronal cell replication and differentiation (Teng and Greene, 1994). In the presence of nerve growth factor (NGF), the cells gradually exit the mitotic cycle and begin to differentiate, developing axonal projections, electrical excitability, and the characteristics of two distinct phenotypes, cholinergic, and catecholaminergic neurons (Fujita et al, 1989;Song et al, 1998;Teng and Greene, 1994). These specific phenotypes are highly targeted by DEX treatment in vivo (Ebert et al, 1997;Hu et al, 1996;Kreider et al, 2005aKreider et al, , b, 2006Reznikov et al, 2004;Slotkin et al, 1991;Zahalka et al, 1993).…”

“…Accordingly, the PC12 model is particularly appropriate to evaluate the mechanisms underlying the effects of DEX on neural cell replication and differentiation into defined phenotypes. Indeed, the medium required to maintain PC12 cell replication, differentiation, and growth entails the use of sera containing endogenous glucocorticoids (Qiao et al, 2005;Song et al, 1998;Teng and Greene, 1994), so that, as with the situation in vivo, effects of DEX are exerted over and above the requisite normal concentration required to maintain neural cell development. At the same time, as with all in vitro models, the cell cultures lack many features common to the developing brain, including the ability to evaluate neuronalglial interactions or more architectural aspects of regional development.…”

“…The effects on cell number, size, and cell surface area were compared to those on viability, evaluated by Trypan blue exclusion. To characterize the cholinergic and catecholaminergic phenotypes, we assessed the activities of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH), the respective biosynthetic enzymes for acetylcholine and dopamine (Teng and Greene, 1994).…”