title: Glutamate-mediated overexpression of CD38 in astrocytes cultured with neurones.
abstract: 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 Ca(2+) concentration [Ca(2+)](i) transients elicit an increased release of glutamate, which can induce an enhanced Ca(2+) 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 [Ca(2+)](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 [Ca(2+)](i) in both cell types, adding further complexity to the bi-directional patterns of communication between astrocytes and neurones.
authors.affiliation: Department of Experimental Medicine, Sections of Biochemistry and Pharmacology, University of Genova, Italy.
authors.forename: Santina
authors.initials: S
authors.lastname: Bruzzone
authors.forename: Claudia
authors.initials: C
authors.lastname: Verderio
authors.forename: Ursula
authors.initials: U
authors.lastname: Schenk
authors.forename: Ernesto
authors.initials: E
authors.lastname: Fedele
authors.forename: Elena
authors.initials: E
authors.lastname: Zocchi
authors.forename: Michela
authors.initials: M
authors.lastname: Matteoli
authors.forename: Antonio
authors.initials: A
authors.lastname: De Flora
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000096:biosynthesis*; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D036563:Cyclic ADP-Ribose / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats
chemical_list: D015703:Antigens, CD; D018691:Excitatory Amino Acid Antagonists; D008562:Membrane Glycoproteins; D036563:Cyclic ADP-Ribose; D018698:Glutamic Acid; C090939:GDP-ribosyl cyclase; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498156:Cd38 protein, rat; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium