Neuronal nitric oxide synthase expression is induced in neocortical astrocytes after spreading depression.

摘要: Since the discovery that nitric oxide (NO) is produced by neurons (Garthwaite et al., 1988) and may function as a neurotransmitter (Bredt Snyder, 1989; Garthwaite 1989) mediator of brain injury (Dawson 1991), much attention has been given to cellular sources this diffusible molecule. Cells produce NO through action at least three isoforms synthase (NOS): neuronal (nNOS), inducible (iNOS), endothelial 1994; Zhang 1995). Neuronal NOS localized discrete regions brain, where expression exclusive 1991; Schmidt 1992); however, in cerebellum hippocampus, nNOS also found astrocytes (Schmidt 1992; Murphy 1993; Kugler Drenckhahn, 1996). In neocortex, expressed small percentage total neurons, mostly residing deeper lamina 1991). The observations subset can express 1992) mRNA could be isolated from derived many (Minc-Golomb Schwartz, suggest throughout have potential nNOS. Knowledge under what circumstances they are able important implications for understanding normal pathologic conditions. Expression induced cell types after variety stimuli. Induction iNOS occurs hepatocytes cytokine stimulation (Geller 1993), cerebral ischemia (Iadecola 1995), body lipopolysaccharide (Liu 1993). Expression increases transient global (Endoh 1994) both microglia vitro various perturbations (e.g., exposure cytokines; Simmons Murphy, 1992). events cause death, such peripheral nerve transection (Fiallos-Estrada Verge Wu (Zhang, 1994a). Nitric activity modulates ischemic (Iadecola, 1997). Intracellular conditions Ca2+, pH) influence which active. Because intracellular glial cells change dramatically during spreading depression (SD) differ significantly surrounding (Kraig Chesler, 1988; Chesler Kraig, Kraig Lascola, knowledge essential their contribution production brain. If neocortical or multiple perturbation, would diversify roles modulating injury. For example, damage reduced nNOS-deficient mice (Huang Panahian 1996; Hara glia vivo similar (such SD), become site potentially involved earlier observation. Furthermore, several studies show (Hewett (Boje Arora. Chao mediates death excitotoxic Thus, identifying isoform further role function. Here we demonstrate SD induces astrocytes. Spreading benign perturbation characterized propagating wave electrical silence negative interstitial direct current (Leao, 1944). It not associated with (Nedergaard Hansen, 1991); it does reactive Gehrmann Caggiano addition transforming into species, enzymes mediators inflammation (Caggiano manipulation shown modulate 1997), sought determine if might induce isoforms, so, source expression. We neocortex experiencing SD, was within 6 hours, stronger 3 days SD. depression-induced limited astrocytes, but all any addition, course determining itself effected expression, blocked treatment animals phenylephrine (PE), an adrenergic agonist used conjunction agents production. These results select population noninjurious prevented agonists.