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Journal of Neuroinflammation

, 13:265

First Online: 11 October 2016Received: 30 May 2016Accepted: 22 September 2016

Abstract

BackgroundNogo-A and its putative receptor NgR are considered to be among the inhibitors of axonal regeneration in the CNS. However, few studies so far have addressed the issue of local NgR complex multilateral localization within inflammation in an MS mouse model of autoimmune demyelination.

MethodsChronic experimental autoimmune encephalomyelitis EAE was induced in C57BL-6 mice. Analyses were performed on acute days 18–22 and chronic day 50 time points and compared to controls. The temporal and spatial expression of the Nogo receptor complex NgR and coreceptors was studied at the spinal cord using epifluorescent and confocal microscopy or real-time PCR. Data are expressed as cells-mm, as mean % ± SEM, or as arbitrary units of integrated density.

ResultsAnimals developed a moderate to severe EAE without mortality, followed by a progressive, chronic clinical course. NgR complex spatial expression varied during the main time points of EAE. NgR with coreceptors LINGO-1 and TROY was increased in the spinal cord in the acute phase whereas LINGO-1 and p75 signal seemed to be dominant in the chronic phase, respectively. NgR was detected on gray matter NeuN neurons of the spinal cord, within the white matter inflammatory foci 14.2 ± 4.3 % NgR inflammatory cells, and found to be colocalized with GAP-43 axonal growth cones while no β-TubIII, SMI-32, or APP axons were found as NgR. Among the NgR inflammatory cells, 75.6 ± 9.0 % were microglial-macrophages lectin, 49.6 ± 14.2 % expressed CD68 phagocytic ED1 cells, and no cells were Mac-3. Of these macrophages-monocytes, only Arginase-1-NgR but not iNOS-NgR were present in lesions both in acute and chronic phases.

ConclusionsOur data describe in detail the expression of the Nogo receptor complex within the autoimmune inflammatory foci and suggest a possible immune action for NgR apart from the established inhibitory one on axonal growth. Its expression by inflammatory macrophages-monocytes could signify a possible role of these cells on axonal guidance and clearance of the lesioned area during inflammatory demyelination.

KeywordsNogo receptor complex NgR LINGO-1 p75 TROY Experimental autoimmune encephalomyelitis Neuroinflammation Macrophages AbbreviationsANOVAAnalysis of variance

APPβ-Amyloid precursor protein

CFAComplete Freund’s adjuvant

CNSCentral nervous system

DAPI4′,6-Diamidino-2-phenylindole

EAEExperimental autoimmune encephalomyelitis

GFAPGlial fibrillary acidic protein

GPIGlycosylphosphatidylinositol

Iba-1Ionized calcium-binding adaptor molecule-1

iNOSInducible nitric oxide synthase

LFBLuxol fast blue

LRRLeucine-rich-repeat

MOGMyelin oligodendrocyte glycoprotein

MSMultiple sclerosis

NeuNNeuronal nuclei

SEMStandard error of the mean

Electronic supplementary materialThe online version of this article doi:10.1186-s12974-016-0730-4 contains supplementary material, which is available to authorized users.

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Autor: Paschalis Theotokis - Olga Touloumi - Roza Lagoudaki - Evangelia Nousiopoulou - Evangelia Kesidou - Spyridon Siafis - Theodo

Fuente: https://link.springer.com/



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