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Immunity and Ageing

, 14:9

First Online: 13 April 2017Received: 08 December 2016Accepted: 05 April 2017DOI: 10.1186-s12979-017-0091-6

Cite this article as: Galbavy, W., Lu, Y., Kaczocha, M. et al. Immun Ageing 2017 14: 9. doi:10.1186-s12979-017-0091-6

Abstract

BackgroundWe have previously reported elevated expression of multiple pro-inflammatory markers in the lumbar spinal cord LSC of middle-aged male rats compared to young adults suggesting a para-inflammatory state develops in the LSC by middle age, a time that in humans is associated with the greatest pain prevalence and persistence. The goal of the current study was to examine the transcriptome-wide gene expression differences between young and middle aged LSC.

MethodsYoung 3 month and middle-aged 17 month naïve Fisher 344 rats n = 5 per group were euthanized, perfused with heparinized saline, and the LSC were removed.

Results~70% of 31,000 coding sequences were detected. After normalization, ~ 1100 showed statistically significant differential expression. Of these genes, 353 middle-aged annotated genes differed by > 1.5 fold compared to the young group. Nearly 10% of these genes belonged to the microglial sensome. Analysis of this subset revealed that the principal age-related differential pathways populated are complement, pattern recognition receptors, OX40, and various T cell regulatory pathways consistent with microglial priming and T cell invasion and modulation. Many of these pathways substantially overlap those previously identified in studies of LSC of young animals with chronic inflammatory or neuropathic pain.

ConclusionsUp-modulation of complement pathway, microglial priming and activation, and T cell-antigen-presenting cell communication in healthy middle-aged LSC was found. Taken together with our previous work, the results support our conclusion that an incipient or para-inflammatory state develops in the LSC in healthy middle-aged adults.

KeywordsTranscriptome Aging Spinal cord Microglia Neuropathic Complement T-cell Inflammation AbbreviationsAPCAntigen presenting cell

CNSCentral nervous system

LSCLumbar spinal cord

qPCRQuantitative polymerase chain reaction

Electronic supplementary materialThe online version of this article doi:10.1186-s12979-017-0091-6 contains supplementary material, which is available to authorized users.

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Autor: William Galbavy - Yong Lu - Martin Kaczocha - Michelino Puopolo - Lixin Liu - Mario J. Rebecchi

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







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