The Contribution of Nitric Oxide and Carbon Monoxide to Neuronal Function and Development

Nitric oxide (NO) and carbomonoxide (CO) are gaseous molecules that have been recently implicated in a series of activities in the nervous system. These cellular messengers function as neurotransmitters, and their neurodegenerative and neuroprotective actions observed in in vitro and in vivo suggest participation of these gases in cell survival and neuronal differentiation. Lack of NO resulted in cell death in neuronal cell lines and is accompanied by neuropathological conditions in animal models. Altered adult neurogenesis was found in NO-synthetase knock-out animals. Moreover, animals with NO-shortage showed defects in hippocampal long term potentiation and retinal map formation. Abnormalities in CO- metabolism and -function are involved in neurodegenerative disease states. This review summarizes the historical record of evidences for NO and CO functions in the nervous system, and describes the participation of these second messengers in the early steps of neuronal differentiation during embryonic development, i.e. migration, dendritic and axonal growth, and synaptogenesis. Moreover, the localization of NO- and CO- synthesis and the intracellular targets of these gases and their downstream targets, such as cGMP and their respective receptors, are discussed. The association of expression of NO- and CO- induced signaling cascades with glutamate receptors activating NO- and CO- production, provides strong evidence regarding the participation of these gases in formation of the nervous system. These mechanisms indicate novel targets for therapeutic intervention in disease states resulting from the lack of NO- and CO-synthesis.