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

Abstract

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 [Ca 2+ ] i . The PP directly activated PC-12 cells and neurons by the release of Ca 2+ from the intracellular stores in a steady manner. The PP also stimulated the entry of Ca 2+ into the cells in a Ca 2+ 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 Ca 2+ 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 Ca 2+ into the cells was observed.

Toll-like Receptors 3, 4, and 7 Are Expressed in the Enteric Nervous System and Dorsal Root Ganglia

“…Physiological “close encounters” between enteric neurons and commensal microbiota are therefore not unlikely and might be at the base of a steady stimulation of neuro-immunomodulatory mechanisms participating in gut homeostasis. Modulatory effects of prebiotics and probiotics on nerve cells have already been demonstrated for enteric neurons (Kamm et al 2004), DRGs (Kamiya et al 2006), and rat brain neurons or pheochromocytoma-differentiated cells (Sobol et al 2005).…”