title: The effects of L-NAME on neuronal NOS and SOD1 expression in the DRG-spinal cord network of axotomised Thy 1.2 eGFP mice.
abstract: Nitric oxide (NO) plays an important role in pathophysiology of the nervous system. Copper/zinc superoxide dismutase (SOD1) reacts with superoxide, which is also a substrate for NO, to provide antioxidative protection. NO production is greatly altered following nerve injury, therefore we hypothesised that SOD1 and NO may be involved in modulating axotomy responses in dorsal root ganglion (DRG)-spinal network. To investigate this interaction, adult Thy1.2 enhanced membrane-bound green fluorescent protein (eGFP) mice underwent sciatic nerve axotomy and received NG-nitro- <l-arginine methylester (L-NAME) or vehicle 7-9 days later. L4-L6 spinal cord and DRG were harvested for immunohistochemical analyses. Effect of injury was confirmed by axotomy markers; small proline-rich repeat protein 1A (SPRR1A) was restricted to ipsilateral neuropathology, while Thy1.2 eGFP revealed also contralateral crossover effects. L-NAME, but not axotomy, increased neuronal NO synthase (nNOS) and SOD1 immunoreactive neurons, with no colocalisation, in a lamina-dependent manner in the dorsal horn of the spinal cord. Axotomy and/or L-NAME had no effect on total nNOS+ and SOD1+ neurons in DRG. However, L-NAME altered SOD1 expression in subsets of axotomised DRG neurons. These findings provide evidence for differential distribution of SOD1 and its modulation by NO, which may interact to regulate axotomy-induced changes in DRG-spinal network.
authors.affiliation: Faculty of Health and Life Sciences, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: Matthew J G
authors.initials: MJ
authors.lastname: Bradman
authors.forename: Richard
authors.initials: R
authors.lastname: Morris
authors.forename: Anne
authors.initials: A
authors.lastname: McArdle
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Jackson
authors.forename: Thimmasettappa
authors.initials: T
authors.lastname: Thippeswamy
mesh_terms: D000818:Animals; D019771:Axotomy / Q000379:methods; D005727:Ganglia, Spinal / Q000187:drug effects / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D049452:Green Fluorescent Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009415:Nerve Net / Q000187:drug effects / Q000201:enzymology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000072105:Superoxide Dismutase-1; D018800:Thy-1 Antigens / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D018800:Thy-1 Antigens; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019331:NG-Nitroarginine Methyl Ester