Dual cross-talk between nitric oxide and D-serine in astrocytes and neurons in the brain.
The present review describes the role of the putative cross-talk between two neurotransmitters, nitric oxide (NO) and D-serine, in the brain. Under physiological conditions NO homeostasis guarantees the correct function of NO in a number of events in the brain such as neurotransmission and vascular tone regulation. D-serine, produced in astrocytes, acts synergistically with glutamate at NMDA receptors on postsynaptic neurons. Neuronal and endothelial NO synthase (nNOS and eNOS) in astrocytes cross-talk with serine racemase (SR) and D-amino acid oxydase (DAAO), catalyzing the synthesis and degradation of D-serine, respectively. SR is inhibited by NO which activates DAAO. D-serine inhibits nNOS but not eNOS and activates SR. Astrocytes and neurons also cross-talk through NO/D-serine system. D-serine released from astrocytes induces a rapid increase in NO contents in postsynaptic neurons. Overall, D-serine production in astrocytes is negatively regulated by NO. Under inflammatory conditions, pro-inflammatory cytokines or Abeta induce, first, a drop in NO contents and an increase in the amounts of D-serine in astrocytes. Together with enhanced glutamate release from presynaptic neurons, D-serine induces an increase in Ca(2+) up-take into presynaptic neurons. In astrocytes an initial drop in NO contents triggers NF-kappaB activation followed by inducible NOS (iNOS) expression. iNOS-derived massive amounts of NO may potentially be toxic. Under schizophrenic conditions, D-serine production is down-regulated. Together with reduced glutamate release, this situation leads to the decreased NO production in postsynaptic neurons. In astrocytes induction of iNOS expression becomes predominant. Initial drop in nNOS-derived NO is potentially toxic in this scenario.
Darra
Elena
E
Dipartimento di Scienze Morphologico-Biomediche, Università di Verona, Italy.
Ebner
Florian Heinrich
FH
Shoji
Kazuo
K
Suzuki
Hisanori
H
Mariotto
Sofia
S
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000166:cytology; D001932:Brain Neoplasms / Q000209:etiology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020239:Receptor Cross-Talk / Q000187:drug effects*; D012694:Serine / Q000737:chemistry / Q000494:pharmacology*; D013312:Stress, Physiological
D016207:Cytokines; D009569:Nitric Oxide; D018698:Glutamic Acid; D012694:Serine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III