Recently, a new system of astrocyte-neurone glutamatergic signalling has been identified. It is started in astrocytes by ectocellular, CD38-catalysed conversion of NAD+ to the calcium mobilizer cyclic ADP-ribose (cADPR). This is then pumped by CD38 itself into the cytosol where the resulting free intracellular Ca2+ concentration [Ca 2+]i transients elicit an increased release of glutamate, which can induce an enhanced Ca2+ response in neighbouring neurones. Here, we demonstrate that co-culture of either cortical or hippocampal astrocytes with neurones results in a significant overexpression of astrocyte CD38 both on the plasma membrane and intracellularly. The causal role of neurone-released glutamate in inducing overexpression of astrocyte CD38 is demonstrated by two observations: first, in the absence of neurones, induction of CD38 in pure astrocyte cultures can be obtained with glutamate and second, it can be prevented in co-cultures by glutamate receptor antagonists. The neuronal glutamate-mediated effect of neurones on astrocyte CD38 expression is paralleled by increased intracellular cADPR and [Ca2+]i levels, both findings indicating functionality of overexpressed CD38. These results reveal a new neurone-to-astrocyte glutamatergic signalling based on the CD38/cADPR system, which affects the [Ca2+]i in both cell types, adding further complexity to the bi-directional patterns of communication between astrocytes and neurones.
|Number of pages||9|
|Journal||Journal of Neurochemistry|
|Publication status||Published - Apr 2004|
- Cyclic ADP-ribose
- Intracellular calcium
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience