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01 February 2004

Nitric oxide modulates microglial activation

George B. Stefano, Ellen Kim, Yu Liu, Wei Zhu, Federico Casares, Kirk J. Mantione, Dolisha Jones, Patrick Cadet

Med Sci Monit 2004; 10(2): BR17-22 :: ID: 11594

Abstract

Background:Nitric oxide (NO) has important physiological regulatory roles, i.e, vasodilation, neurotransmitter release, etc. Little is known about the processes in neural tissues, which stabilize microglia. This study attempts to answer this question by demonstrating a role for basal NO in maintaining microglia juxtaposed to neurons.Material/Methods: Mytilus edulis (a marine bivalve), were used to examine microglia egress from excised pedal ganglia microscopically. Nitric oxide is measured in excised pedal ganglia amperometrically in real-time.Results: Pedal ganglia exhibit basal NO release (1 nM range). Inhibition of basal NO release by L-NAME results in greater numbers of microglia in the incubation medium. This process appears to involve two phases of egress. The first involves a slow egress of microglia, whereas the second, occurring 18 hours later, involves a more rapid release of these cells. Low levels of the NO donor SNAP (1 nM) does not interrupt microglial egress, whereas in the presence of L-NAME it does. Exposing the ganglia to high NO levels for a short period of time inhibits their egress.Conclusions: Spontaneous ganglionic NO release maintains/stabilizes microglia juxtaposed to neurons. Excised ganglia at the various observation periods reveals a transition of constitutive nitric oxide synthase (NOS) to inducible NOS derived NO. It also appears that the microglia in some unknown manner become insensitive to iNOS derived NO since they exhibit enhanced migration during this last phase of the ganglionic NO response. Taken together, NO is involved with regulating microglial activation.

Keywords: Microglia - metabolism, Animals, Bivalvia - cytology, Electrochemistry - methods, Enzyme Inhibitors - pharmacology, Ganglia, Invertebrate - metabolism, Microglia - physiology, NG-Nitroarginine Methyl Ester - pharmacology, Nitric Oxide - physiology, Nitric Oxide Donors - pharmacology, Penicillamine - pharmacology

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