Purinergic signalling between axons and microglia.

Neurons are delicate elements unable to withstand prolonged exposure to the many toxic factors that gain access to the CNS or which are made by activated leukocytes. The well-being of neurons and their functional properties are dependent on glial cells. Microglia have a unique role in this context because they are involved in both neuronal support and immunological defence. We now know that neuron-microglia communication is bidirectional: neurons and microglia continuously exchange messages and integrate information received from neighbouring cells. It is now generally accepted that purinergic signalling is a key pathway in this continuous flow of information in health and disease. Release of ATP from neurons directly modulates microglial cell function eliciting secretion of neurotrophic or, in some cases, neurotoxic factors that deeply affect neuronal physiology. Purinergic stimulation of microglia P2 receptors might in turn elicit a burst of ATP release that feeds back onto the neurons. Development of sophisticated techniques for the measurement of extracellular ATP now makes possible real-time measurement of ATP release into the pericellular space and allows validation of the purinergic hypothesis for neuron-microglia signalling.