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Complex Inflammation mRNA-Related Response in ALS Is Region Dependent.

Berjaoui S, Povedano M, Garcia-Esparcia P, Carmona M, Aso E, Ferrer I - Neural Plast. (2015)

Bottom Line: Increased numbers of astrocytes and activated microglia are found in the anterior horn of the spinal cord and pyramidal tracts.Significant increased expression of TLR7, CTSS, and CTSC mRNA and a trend to increased expression of IL10RA, TGFB1, and TGFB2 are found in the anterior lumbar spinal cord in ALS cases compared to control cases, whereas C1QTNF7 and TNFRSF1A mRNA expression levels are significantly decreased.IL-6 immunoreactivity is found in scattered monocyte-derived macrophages/microglia and TNF-α in a few cells of unknown origin in ALS cases.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuropathology, Bellvitge University Hospital, University of Barcelona, CIBERNED (Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas), 08907 L'Hospitalet de Llobregat, Spain.

ABSTRACT
Inflammatory changes are analyzed in the anterior spinal cord and frontal cortex area 8 in typical spinal-predominant ALS cases. Increased numbers of astrocytes and activated microglia are found in the anterior horn of the spinal cord and pyramidal tracts. Significant increased expression of TLR7, CTSS, and CTSC mRNA and a trend to increased expression of IL10RA, TGFB1, and TGFB2 are found in the anterior lumbar spinal cord in ALS cases compared to control cases, whereas C1QTNF7 and TNFRSF1A mRNA expression levels are significantly decreased. IL6 is significantly upregulated and IL1B shows a nonsignificant increased expression in frontal cortex area 8 in ALS cases. IL-6 immunoreactivity is found in scattered monocyte-derived macrophages/microglia and TNF-α in a few cells of unknown origin in ALS cases. Increased expression and abnormal distribution of IL-1β occurred in motor neurons of the lumbar spinal cord in ALS. Strong IL-10 immunoreactivity colocalizes with TDP-43-positive inclusions in motor neurons in ALS cases. The present observations show a complex participation of cytokines and mediators of the inflammatory response in ALS consistent with increased proinflammatory cytokines and sequestration of anti-inflammatory IL-10 in affected neurons.

No MeSH data available.


Related in: MedlinePlus

(a–c): CD68 immunohistochemistry shows amoeboid monocyte derived macrophages/microglia in the anterior lumbar horn (a and b) and pyramidal tracts (c) of the lumbar spinal cord in control (a) and ALS (b and c). (d and e) IBA1 stains immunoreactivity is present in large numbers of monocyte derived macrophages/microglia in the lateral pyramidal tract in control (D) and ALS cases with predominance of amoeboid cells in disease. (f) TNF-α is localized in a few round cells of undetermined origin. (g–i) IL-6 immunoreactivity is found in the wall of blood vessels (g) and in scattered microglial cells (h and i). (j and k) IL-1β immunoreactivity is present in neurons in control (j) and ALS cases but increased immunoreactivity and abnormal distribution of IL-1β is observed in a few motor neurons of the lumbar spinal cord only in ALS (k). (l–o) Strong IL-10 immunoreactivity is seen in cytoplasmic inclusions in ALS reminiscent of ubiquitinated, TDP-43-positive inclusions currently found in motor neurons in sALS. Paraffin sections, slight haematoxylin counterstaining, bar in (o) valid for all figures = 30 µm, excepting bar in F = 50 µm.
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fig2: (a–c): CD68 immunohistochemistry shows amoeboid monocyte derived macrophages/microglia in the anterior lumbar horn (a and b) and pyramidal tracts (c) of the lumbar spinal cord in control (a) and ALS (b and c). (d and e) IBA1 stains immunoreactivity is present in large numbers of monocyte derived macrophages/microglia in the lateral pyramidal tract in control (D) and ALS cases with predominance of amoeboid cells in disease. (f) TNF-α is localized in a few round cells of undetermined origin. (g–i) IL-6 immunoreactivity is found in the wall of blood vessels (g) and in scattered microglial cells (h and i). (j and k) IL-1β immunoreactivity is present in neurons in control (j) and ALS cases but increased immunoreactivity and abnormal distribution of IL-1β is observed in a few motor neurons of the lumbar spinal cord only in ALS (k). (l–o) Strong IL-10 immunoreactivity is seen in cytoplasmic inclusions in ALS reminiscent of ubiquitinated, TDP-43-positive inclusions currently found in motor neurons in sALS. Paraffin sections, slight haematoxylin counterstaining, bar in (o) valid for all figures = 30 µm, excepting bar in F = 50 µm.

Mentions: CD68 immunohistochemistry revealed that the phenotype of monocyte derived macrophages/microglia was ramified and amoeboid in the anterior lumbar horn, anterior root, and direct and crossed pyramidal tracts of the spinal cord in ALS (Figures 1(a)–1(c)). Differences in number were assessed regarding IBA1-immunoreactive cells; increased numbers of monocyte derived macrophages/microglia (543.1 ± 36.2 cells/mm2 in ALS versus 312.6 ± 19.3 cells/mm2 in controls), in addition to high predominance of amoeboid cells, were found in the pyramidal tracts of the spinal cord in ALS (Figures 2(d) and 2(e)). Yet TNF-α was restricted to a few round cells of unknown origin (Figure 2(f)). Strong IL-6 immunoreactivity occurred in the wall of the blood vessels (Figure 2(g)) and in scattered glial cells with the morphology of microglia/macrophage in ALS (Figures 2(g) and 2(h)). Increased IL-1β immunoreactivity was observed in motor neurons in ALS (118.7 ± 24.5 cells/mm2) when compared to controls (64.3 ± 15.0 cells/mm2); abnormal distribution of IL-1β was also found in a few motor neurons of the lumbar spinal cord only in ALS (Figures 2(i) and 2(j)). IL-10 immunoreactivity was present in neurons in control (41.5 ± 4.3 cells/mm2) and ALS cases (63.5 ± 20.2 cells/mm2). Curiously, increased IL-10 immunoreactivity was seen in cytoplasmic inclusions reminiscent of ubiquitinated, TDP-43-positive inclusions currently seen in motor neurons in sALS (Figures 2(k)–2(o)).


Complex Inflammation mRNA-Related Response in ALS Is Region Dependent.

Berjaoui S, Povedano M, Garcia-Esparcia P, Carmona M, Aso E, Ferrer I - Neural Plast. (2015)

(a–c): CD68 immunohistochemistry shows amoeboid monocyte derived macrophages/microglia in the anterior lumbar horn (a and b) and pyramidal tracts (c) of the lumbar spinal cord in control (a) and ALS (b and c). (d and e) IBA1 stains immunoreactivity is present in large numbers of monocyte derived macrophages/microglia in the lateral pyramidal tract in control (D) and ALS cases with predominance of amoeboid cells in disease. (f) TNF-α is localized in a few round cells of undetermined origin. (g–i) IL-6 immunoreactivity is found in the wall of blood vessels (g) and in scattered microglial cells (h and i). (j and k) IL-1β immunoreactivity is present in neurons in control (j) and ALS cases but increased immunoreactivity and abnormal distribution of IL-1β is observed in a few motor neurons of the lumbar spinal cord only in ALS (k). (l–o) Strong IL-10 immunoreactivity is seen in cytoplasmic inclusions in ALS reminiscent of ubiquitinated, TDP-43-positive inclusions currently found in motor neurons in sALS. Paraffin sections, slight haematoxylin counterstaining, bar in (o) valid for all figures = 30 µm, excepting bar in F = 50 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig2: (a–c): CD68 immunohistochemistry shows amoeboid monocyte derived macrophages/microglia in the anterior lumbar horn (a and b) and pyramidal tracts (c) of the lumbar spinal cord in control (a) and ALS (b and c). (d and e) IBA1 stains immunoreactivity is present in large numbers of monocyte derived macrophages/microglia in the lateral pyramidal tract in control (D) and ALS cases with predominance of amoeboid cells in disease. (f) TNF-α is localized in a few round cells of undetermined origin. (g–i) IL-6 immunoreactivity is found in the wall of blood vessels (g) and in scattered microglial cells (h and i). (j and k) IL-1β immunoreactivity is present in neurons in control (j) and ALS cases but increased immunoreactivity and abnormal distribution of IL-1β is observed in a few motor neurons of the lumbar spinal cord only in ALS (k). (l–o) Strong IL-10 immunoreactivity is seen in cytoplasmic inclusions in ALS reminiscent of ubiquitinated, TDP-43-positive inclusions currently found in motor neurons in sALS. Paraffin sections, slight haematoxylin counterstaining, bar in (o) valid for all figures = 30 µm, excepting bar in F = 50 µm.
Mentions: CD68 immunohistochemistry revealed that the phenotype of monocyte derived macrophages/microglia was ramified and amoeboid in the anterior lumbar horn, anterior root, and direct and crossed pyramidal tracts of the spinal cord in ALS (Figures 1(a)–1(c)). Differences in number were assessed regarding IBA1-immunoreactive cells; increased numbers of monocyte derived macrophages/microglia (543.1 ± 36.2 cells/mm2 in ALS versus 312.6 ± 19.3 cells/mm2 in controls), in addition to high predominance of amoeboid cells, were found in the pyramidal tracts of the spinal cord in ALS (Figures 2(d) and 2(e)). Yet TNF-α was restricted to a few round cells of unknown origin (Figure 2(f)). Strong IL-6 immunoreactivity occurred in the wall of the blood vessels (Figure 2(g)) and in scattered glial cells with the morphology of microglia/macrophage in ALS (Figures 2(g) and 2(h)). Increased IL-1β immunoreactivity was observed in motor neurons in ALS (118.7 ± 24.5 cells/mm2) when compared to controls (64.3 ± 15.0 cells/mm2); abnormal distribution of IL-1β was also found in a few motor neurons of the lumbar spinal cord only in ALS (Figures 2(i) and 2(j)). IL-10 immunoreactivity was present in neurons in control (41.5 ± 4.3 cells/mm2) and ALS cases (63.5 ± 20.2 cells/mm2). Curiously, increased IL-10 immunoreactivity was seen in cytoplasmic inclusions reminiscent of ubiquitinated, TDP-43-positive inclusions currently seen in motor neurons in sALS (Figures 2(k)–2(o)).

Bottom Line: Increased numbers of astrocytes and activated microglia are found in the anterior horn of the spinal cord and pyramidal tracts.Significant increased expression of TLR7, CTSS, and CTSC mRNA and a trend to increased expression of IL10RA, TGFB1, and TGFB2 are found in the anterior lumbar spinal cord in ALS cases compared to control cases, whereas C1QTNF7 and TNFRSF1A mRNA expression levels are significantly decreased.IL-6 immunoreactivity is found in scattered monocyte-derived macrophages/microglia and TNF-α in a few cells of unknown origin in ALS cases.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuropathology, Bellvitge University Hospital, University of Barcelona, CIBERNED (Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas), 08907 L'Hospitalet de Llobregat, Spain.

ABSTRACT
Inflammatory changes are analyzed in the anterior spinal cord and frontal cortex area 8 in typical spinal-predominant ALS cases. Increased numbers of astrocytes and activated microglia are found in the anterior horn of the spinal cord and pyramidal tracts. Significant increased expression of TLR7, CTSS, and CTSC mRNA and a trend to increased expression of IL10RA, TGFB1, and TGFB2 are found in the anterior lumbar spinal cord in ALS cases compared to control cases, whereas C1QTNF7 and TNFRSF1A mRNA expression levels are significantly decreased. IL6 is significantly upregulated and IL1B shows a nonsignificant increased expression in frontal cortex area 8 in ALS cases. IL-6 immunoreactivity is found in scattered monocyte-derived macrophages/microglia and TNF-α in a few cells of unknown origin in ALS cases. Increased expression and abnormal distribution of IL-1β occurred in motor neurons of the lumbar spinal cord in ALS. Strong IL-10 immunoreactivity colocalizes with TDP-43-positive inclusions in motor neurons in ALS cases. The present observations show a complex participation of cytokines and mediators of the inflammatory response in ALS consistent with increased proinflammatory cytokines and sequestration of anti-inflammatory IL-10 in affected neurons.

No MeSH data available.


Related in: MedlinePlus