Calcium Signalling in Rat Brain Neurons and Differentiation of PC-12 Cells Induced by Application of a Probiotic Product

The effects of a biotechnological probiotic product, PP, produced by food fermentation with Lactobacilli (US patent approved), on the growth of neurites in rat pheochromocytoma cells (PC-12) and on calcium responses of rat brain neurons were studied in culture. The PP increased the length of neurites in PC-12 cells, resulting in an irreversible differentiation of cancerous cells into neuron-like structures. Moreover, a change in the neurotransmitter phenotype of differentiated cells was found; some cells, such as excitatory neurons, began to respond to glutamate application by increasing [Ca2+](i). The PP directly activated PC-12 cells and neurons by the release of Ca2+ from the intracellular stores in a steady manner. The PP also stimulated the entry of Ca2+ into the cells in a Ca2+ add-back protocol, which was considerable upon washing out of PP. Thus, the products of Lactobacillus metabolism, such as those in PP, can act as a neuronal growth factor and manifest clear pharmacological reactions at the cellular level. By comparison, commercial lyophilized probiotic bacteria also induced a Ca2+ rise in neurons, but not in PC-12 cells. Some neurons did not respond to probiotic bacteria, and some neurons responded with some delay. Upon wash out of probiotic bacteria, a huge entry of Ca2+ into the cells was observed.