Dataset Information

An Intimate Role for Adult Dorsal Root Ganglia Resident Cycling Cells in the Generation of Local Macrophages and Satellite Glial Cells.

ABSTRACT: The intricate interactions between neurons, glial, and inflammatory cells within peripheral ganglia are physiologically important, but not well explored. Here, we show that adult dorsal root ganglia (DRG) contain populations of self-renewing cells, collectively referred as DRG resident cycling cells (DRCCs), that are active not only in "quiescent" ganglia but also accelerate their turnover in response to distal axotomy. An unexpected proportion of DRCCs were resident macrophages. These cells closely accompanied, and aligned with recycling satellite glial cells (SGCs) that were juxtaposed to sensory neurons and possessed stem cell-like properties. Selective inhibition of colony stimulating factor 1 receptor prevented the local proliferation of macrophages. Interestingly, DRCC turnover was accompanied by apoptosis at later intervals indicating a balanced cellular milieu in the DRGs. These findings identify a complex interactive multicellular DRG microenvironment supporting self-renewal of both macrophages and SGCs and its potential implications in the overall response of adult DRGs to injury.

SUBMITTER: Krishnan A

PROVIDER: S-EPMC6140451 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

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An Intimate Role for Adult Dorsal Root Ganglia Resident Cycling Cells in the Generation of Local Macrophages and Satellite Glial Cells.

Krishnan Anand A Bhavanam Sudha S Zochodne Douglas D

Journal of neuropathology and experimental neurology 20181001 10

The intricate interactions between neurons, glial, and inflammatory cells within peripheral ganglia are physiologically important, but not well explored. Here, we show that adult dorsal root ganglia (DRG) contain populations of self-renewing cells, collectively referred as DRG resident cycling cells (DRCCs), that are active not only in "quiescent" ganglia but also accelerate their turnover in response to distal axotomy. An unexpected proportion of DRCCs were resident macrophages. These cells clo ...[more]

PMID: 30169768

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Project description:BackgroundRobust activation of glial cells has been reported to occur particularly during the pathogenesis of bone cancer pain (BCP). Researchers from our group and others have shown that histone deacetylases (HDACs) play a significant role in modulating glia-mediated immune responses; however, it still remains unclear whether HDACs are involved in the activation of glial cells during the development of BCP.MethodsBCP model was established by intra-tibia tumor cell inoculation (TCI). The expression levels and distribution sites of histone deacetylases (HDACs) in the spinal dorsal horn and dorsal root ganglia were evaluated by Western blot and immunofluorescent staining, respectively. Suberoylanilide hydroxamic acid (SAHA), a clinically used HDAC inhibitor, was then intraperitoneally and intrathecally injected to rescue the increased expression levels of HDAC1 and HDAC2. The analgesic effects of SAHA administration on BCP were then evaluated by measuring the paw withdrawal thresholds (PWTs). The effects of SAHA on activation of glial cells and expression of proinflammatory cytokines (TNF-?, IL-1?, and IL-6) in the spinal dorsal horn and dorsal root ganglia of TCI rats were further evaluated by immunofluorescent staining and Western blot analysis. Subsequently, the effects of SAHA administration on tumor growth and cancer cell-induced bone destruction were analyzed by hematoxylin and eosin (HE) staining and micro-CT scanning.ResultsTCI caused rapid and long-lasting increased expression of HDAC1/HDAC2 in glial cells of the spinal dorsal horn and dorsal root ganglia. Inhibiting HDACs by SAHA not only reversed TCI-induced upregulation of HDACs but also inhibited the activation of glial cells in the spinal dorsal horn and dorsal root ganglia, and relieved TCI-induced mechanical allodynia. Further, we found that SAHA administration could not prevent cancer infiltration or bone destruction in the tibia, which indicated that the analgesic effects of SAHA were not due to its anti-tumor effects. Moreover, we found that SAHA administration could inhibit GSK3? activity in the spinal dorsal horn and dorsal root ganglia, which might contributed to the relief of BCP.ConclusionOur findings suggest that HDAC1 and HDAC2 are involved in the glia-mediated neuroinflammation in the spinal dorsal horn and dorsal root ganglia underlying the pathogenesis of BCP, which indicated that inhibiting HDACs by SAHA might be a potential strategy for pain relief of BCP.

Dataset Information

An Intimate Role for Adult Dorsal Root Ganglia Resident Cycling Cells in the Generation of Local Macrophages and Satellite Glial Cells.

Publications

An Intimate Role for Adult Dorsal Root Ganglia Resident Cycling Cells in the Generation of Local Macrophages and Satellite Glial Cells.

Similar Datasets

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