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Neuroimmune and Neuropathic Responses of Spinal Cord and Dorsal Root Ganglia in Middle Age.

Galbavy W, Kaczocha M, Puopolo M, Liu L, Rebecchi MJ - PLoS ONE (2015)

Bottom Line: Results showed that CD2, CD3e, CD68, CD45, TNF-α, IL6, CCL2, ATF3 and TGFβ1 mRNA levels were substantially elevated in LSC from naïve middle-aged animals compared to young adults.The patterns of marker expression and microglial morphologies in healthy middle age are consistent with development of a para-inflammatory state involving microglial activation and T-cell marker elevation in the dorsal horn, and neuronal stress and satellite cell activation in the DRG.These changes, however, did not affect the establishment of neuropathic pain.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Stony Brook University, Stony Brook, New York, United States of America.

ABSTRACT
Prior studies of aging and neuropathic injury have focused on senescent animals compared to young adults, while changes in middle age, particularly in the dorsal root ganglia (DRG), have remained largely unexplored. 14 neuroimmune mRNA markers, previously associated with peripheral nerve injury, were measured in multiplex assays of lumbar spinal cord (LSC), and DRG from young and middle-aged (3, 17 month) naïve rats, or from rats subjected to chronic constriction injury (CCI) of the sciatic nerve (after 7 days), or from aged-matched sham controls. Results showed that CD2, CD3e, CD68, CD45, TNF-α, IL6, CCL2, ATF3 and TGFβ1 mRNA levels were substantially elevated in LSC from naïve middle-aged animals compared to young adults. Similarly, LSC samples from older sham animals showed increased levels of T-cell and microglial/macrophage markers. CCI induced further increases in CCL2, and IL6, and elevated ATF3 mRNA levels in LSC of young and middle-aged adults. Immunofluorescence images of dorsal horn microglia from middle-aged naïve or sham rats were typically hypertrophic with mostly thickened, de-ramified processes, similar to microglia following CCI. Unlike the spinal cord, marker expression profiles in naïve DRG were unchanged across age (except increased ATF3); whereas, levels of GFAP protein, localized to satellite glia, were highly elevated in middle age, but independent of nerve injury. Most neuroimmune markers were elevated in DRG following CCI in young adults, yet middle-aged animals showed little response to injury. No age-related changes in nociception (heat, cold, mechanical) were observed in naïve adults, or at days 3 or 7 post-CCI. The patterns of marker expression and microglial morphologies in healthy middle age are consistent with development of a para-inflammatory state involving microglial activation and T-cell marker elevation in the dorsal horn, and neuronal stress and satellite cell activation in the DRG. These changes, however, did not affect the establishment of neuropathic pain.

No MeSH data available.


Related in: MedlinePlus

Neuroimmune gene expression profile in lumbar spinal cords of naïve young and middle-aged rats.Expression levels were normalized to the geomean of Hprt1 and Pplb expression and the ratios multiplied by 100. Results are presented as means +/- SD. Significance of differences between YN v MN * p < 0.0015.
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pone.0134394.g001: Neuroimmune gene expression profile in lumbar spinal cords of naïve young and middle-aged rats.Expression levels were normalized to the geomean of Hprt1 and Pplb expression and the ratios multiplied by 100. Results are presented as means +/- SD. Significance of differences between YN v MN * p < 0.0015.

Mentions: Many of these markers were significantly elevated in the LSC of middle-aged naïve adults (Fig 1), particularly T cell and microglial/macrophage markers, ATF3 (stress), as well as TNFα, a pro-inflammatory cytokine, and CCL2, a chemokine implicated in microglial activation and establishment of neuropathic pain [31]. Up-modulation of TGFβ1, a powerful anti-inflammatory immunomodulator [43], was also observed. In DRG, however, only ATF3 was elevated in middle age (Table 1).


Neuroimmune and Neuropathic Responses of Spinal Cord and Dorsal Root Ganglia in Middle Age.

Galbavy W, Kaczocha M, Puopolo M, Liu L, Rebecchi MJ - PLoS ONE (2015)

Neuroimmune gene expression profile in lumbar spinal cords of naïve young and middle-aged rats.Expression levels were normalized to the geomean of Hprt1 and Pplb expression and the ratios multiplied by 100. Results are presented as means +/- SD. Significance of differences between YN v MN * p < 0.0015.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524632&req=5

pone.0134394.g001: Neuroimmune gene expression profile in lumbar spinal cords of naïve young and middle-aged rats.Expression levels were normalized to the geomean of Hprt1 and Pplb expression and the ratios multiplied by 100. Results are presented as means +/- SD. Significance of differences between YN v MN * p < 0.0015.
Mentions: Many of these markers were significantly elevated in the LSC of middle-aged naïve adults (Fig 1), particularly T cell and microglial/macrophage markers, ATF3 (stress), as well as TNFα, a pro-inflammatory cytokine, and CCL2, a chemokine implicated in microglial activation and establishment of neuropathic pain [31]. Up-modulation of TGFβ1, a powerful anti-inflammatory immunomodulator [43], was also observed. In DRG, however, only ATF3 was elevated in middle age (Table 1).

Bottom Line: Results showed that CD2, CD3e, CD68, CD45, TNF-α, IL6, CCL2, ATF3 and TGFβ1 mRNA levels were substantially elevated in LSC from naïve middle-aged animals compared to young adults.The patterns of marker expression and microglial morphologies in healthy middle age are consistent with development of a para-inflammatory state involving microglial activation and T-cell marker elevation in the dorsal horn, and neuronal stress and satellite cell activation in the DRG.These changes, however, did not affect the establishment of neuropathic pain.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Stony Brook University, Stony Brook, New York, United States of America.

ABSTRACT
Prior studies of aging and neuropathic injury have focused on senescent animals compared to young adults, while changes in middle age, particularly in the dorsal root ganglia (DRG), have remained largely unexplored. 14 neuroimmune mRNA markers, previously associated with peripheral nerve injury, were measured in multiplex assays of lumbar spinal cord (LSC), and DRG from young and middle-aged (3, 17 month) naïve rats, or from rats subjected to chronic constriction injury (CCI) of the sciatic nerve (after 7 days), or from aged-matched sham controls. Results showed that CD2, CD3e, CD68, CD45, TNF-α, IL6, CCL2, ATF3 and TGFβ1 mRNA levels were substantially elevated in LSC from naïve middle-aged animals compared to young adults. Similarly, LSC samples from older sham animals showed increased levels of T-cell and microglial/macrophage markers. CCI induced further increases in CCL2, and IL6, and elevated ATF3 mRNA levels in LSC of young and middle-aged adults. Immunofluorescence images of dorsal horn microglia from middle-aged naïve or sham rats were typically hypertrophic with mostly thickened, de-ramified processes, similar to microglia following CCI. Unlike the spinal cord, marker expression profiles in naïve DRG were unchanged across age (except increased ATF3); whereas, levels of GFAP protein, localized to satellite glia, were highly elevated in middle age, but independent of nerve injury. Most neuroimmune markers were elevated in DRG following CCI in young adults, yet middle-aged animals showed little response to injury. No age-related changes in nociception (heat, cold, mechanical) were observed in naïve adults, or at days 3 or 7 post-CCI. The patterns of marker expression and microglial morphologies in healthy middle age are consistent with development of a para-inflammatory state involving microglial activation and T-cell marker elevation in the dorsal horn, and neuronal stress and satellite cell activation in the DRG. These changes, however, did not affect the establishment of neuropathic pain.

No MeSH data available.


Related in: MedlinePlus