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Astroglia-Microglia Cross Talk during Neurodegeneration in the Rat Hippocampus.

Batlle M, Ferri L, Andrade C, Ortega FJ, Vidal-Taboada JM, Pugliese M, Mahy N, Rodríguez MJ - Biomed Res Int (2015)

Bottom Line: Microglial glucocorticoid receptor expression increased up to day 5, before returning progressively to sham values.We observed a striking maintenance of neuronal death associated with enhanced microglial reaction and proliferation, increased YM1 concentration, and decreased TNF-α secretion and glucocorticoid receptor expression.S100B reactivity only increased after astroglia recovery.

View Article: PubMed Central - PubMed

Affiliation: Unitat de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), C/Casanova 143, 08036 Barcelona, Spain.

ABSTRACT
Brain injury triggers a progressive inflammatory response supported by a dynamic astroglia-microglia interplay. We investigated the progressive chronic features of the astroglia-microglia cross talk in the perspective of neuronal effects in a rat model of hippocampal excitotoxic injury. N-Methyl-D-aspartate (NMDA) injection triggered a process characterized within 38 days by atrophy, neuronal loss, and fast astroglia-mediated S100B increase. Microglia reaction varied with the lesion progression. It presented a peak of tumor necrosis factor-α (TNF-α) secretion at one day after the lesion, and a transient YM1 secretion within the first three days. Microglial glucocorticoid receptor expression increased up to day 5, before returning progressively to sham values. To further investigate the astroglia role in the microglia reaction, we performed concomitant transient astroglia ablation with L-α-aminoadipate and NMDA-induced lesion. We observed a striking maintenance of neuronal death associated with enhanced microglial reaction and proliferation, increased YM1 concentration, and decreased TNF-α secretion and glucocorticoid receptor expression. S100B reactivity only increased after astroglia recovery. Our results argue for an initial neuroprotective microglial reaction, with a direct astroglial control of the microglial cytotoxic response. We propose the recovery of the astroglia-microglia cross talk as a tissue priority conducted to ensure a proper cellular coordination that retails brain damage.

No MeSH data available.


Related in: MedlinePlus

α-AA effect on the NMDA-induced microglial reaction in the hippocampus. (a) Quantification of the hippocampal area of microglial reaction in IB4-stained sections of sham (PBS), α-AA, NMDA, and α-AA + NMDA rats at postlesion days 1, 3, 15, and 38. Photomicrographs show hippocampal IB4-stained cells illustrating different microglial morphology between NMDA (b) and α-AA + NMDA (c) rats 3 days after the lesion. (d) TNF-α hippocampal concentration in PBS, α-AA, NMDA, and α-AA + NMDA rats during the first 5 days of the study. (e) Immunoblots and densitometric analysis (graphs) of YM1 in the hippocampus of PBS, α-AA, NMDA, and α-AA + NMDA rats during the first 5 days of the study. Values were normalized to β-actin bands. (f) Quantification of the nucleus/cytoplasm ratio of GR-immunolabeling in hippocampal glial cells 3 days after the lesion of the four groups of the study. P, PBS; A, α-AA; N, NMDA; NA, α-AA + NMDA; ∗P < 0.05 different from PBS; #P < 0.05 different from NMDA; $P < 0.05 different from α-AA (LSD post hoc test in (a), (e); Student's t-test in (d), (f)) (n = 6 rats/group). Bar: 10 μm.
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fig5: α-AA effect on the NMDA-induced microglial reaction in the hippocampus. (a) Quantification of the hippocampal area of microglial reaction in IB4-stained sections of sham (PBS), α-AA, NMDA, and α-AA + NMDA rats at postlesion days 1, 3, 15, and 38. Photomicrographs show hippocampal IB4-stained cells illustrating different microglial morphology between NMDA (b) and α-AA + NMDA (c) rats 3 days after the lesion. (d) TNF-α hippocampal concentration in PBS, α-AA, NMDA, and α-AA + NMDA rats during the first 5 days of the study. (e) Immunoblots and densitometric analysis (graphs) of YM1 in the hippocampus of PBS, α-AA, NMDA, and α-AA + NMDA rats during the first 5 days of the study. Values were normalized to β-actin bands. (f) Quantification of the nucleus/cytoplasm ratio of GR-immunolabeling in hippocampal glial cells 3 days after the lesion of the four groups of the study. P, PBS; A, α-AA; N, NMDA; NA, α-AA + NMDA; ∗P < 0.05 different from PBS; #P < 0.05 different from NMDA; $P < 0.05 different from α-AA (LSD post hoc test in (a), (e); Student's t-test in (d), (f)) (n = 6 rats/group). Bar: 10 μm.

Mentions: In the α-AA group, the histochemistry with IB4 stained morphologically reactive microglia already at day 1 in an area that reached a maximal value at day 3, before decreasing to sham group values at day 38 (Figure 5(a)). In NMDA-lesioned group the area of microglial reactivity reached significance at day 1 and increased by day 15 and then decreased at day 38 (Figure 5(a)). In the α-AA + NMDA group, microglial reactivity was already significant at day 1 and covered a maximal area at day 3, to then progressively decrease at day 38 (Figure 5(a)). At days 1 and 3, reactive microglia of the α-AA + NMDA group presented a ramified morphology clearly different to the shape showed by microglial cells of the NMDA group, which presented clear reduction of processes (Figures 5(b) and 5(c)).


Astroglia-Microglia Cross Talk during Neurodegeneration in the Rat Hippocampus.

Batlle M, Ferri L, Andrade C, Ortega FJ, Vidal-Taboada JM, Pugliese M, Mahy N, Rodríguez MJ - Biomed Res Int (2015)

α-AA effect on the NMDA-induced microglial reaction in the hippocampus. (a) Quantification of the hippocampal area of microglial reaction in IB4-stained sections of sham (PBS), α-AA, NMDA, and α-AA + NMDA rats at postlesion days 1, 3, 15, and 38. Photomicrographs show hippocampal IB4-stained cells illustrating different microglial morphology between NMDA (b) and α-AA + NMDA (c) rats 3 days after the lesion. (d) TNF-α hippocampal concentration in PBS, α-AA, NMDA, and α-AA + NMDA rats during the first 5 days of the study. (e) Immunoblots and densitometric analysis (graphs) of YM1 in the hippocampus of PBS, α-AA, NMDA, and α-AA + NMDA rats during the first 5 days of the study. Values were normalized to β-actin bands. (f) Quantification of the nucleus/cytoplasm ratio of GR-immunolabeling in hippocampal glial cells 3 days after the lesion of the four groups of the study. P, PBS; A, α-AA; N, NMDA; NA, α-AA + NMDA; ∗P < 0.05 different from PBS; #P < 0.05 different from NMDA; $P < 0.05 different from α-AA (LSD post hoc test in (a), (e); Student's t-test in (d), (f)) (n = 6 rats/group). Bar: 10 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig5: α-AA effect on the NMDA-induced microglial reaction in the hippocampus. (a) Quantification of the hippocampal area of microglial reaction in IB4-stained sections of sham (PBS), α-AA, NMDA, and α-AA + NMDA rats at postlesion days 1, 3, 15, and 38. Photomicrographs show hippocampal IB4-stained cells illustrating different microglial morphology between NMDA (b) and α-AA + NMDA (c) rats 3 days after the lesion. (d) TNF-α hippocampal concentration in PBS, α-AA, NMDA, and α-AA + NMDA rats during the first 5 days of the study. (e) Immunoblots and densitometric analysis (graphs) of YM1 in the hippocampus of PBS, α-AA, NMDA, and α-AA + NMDA rats during the first 5 days of the study. Values were normalized to β-actin bands. (f) Quantification of the nucleus/cytoplasm ratio of GR-immunolabeling in hippocampal glial cells 3 days after the lesion of the four groups of the study. P, PBS; A, α-AA; N, NMDA; NA, α-AA + NMDA; ∗P < 0.05 different from PBS; #P < 0.05 different from NMDA; $P < 0.05 different from α-AA (LSD post hoc test in (a), (e); Student's t-test in (d), (f)) (n = 6 rats/group). Bar: 10 μm.
Mentions: In the α-AA group, the histochemistry with IB4 stained morphologically reactive microglia already at day 1 in an area that reached a maximal value at day 3, before decreasing to sham group values at day 38 (Figure 5(a)). In NMDA-lesioned group the area of microglial reactivity reached significance at day 1 and increased by day 15 and then decreased at day 38 (Figure 5(a)). In the α-AA + NMDA group, microglial reactivity was already significant at day 1 and covered a maximal area at day 3, to then progressively decrease at day 38 (Figure 5(a)). At days 1 and 3, reactive microglia of the α-AA + NMDA group presented a ramified morphology clearly different to the shape showed by microglial cells of the NMDA group, which presented clear reduction of processes (Figures 5(b) and 5(c)).

Bottom Line: Microglial glucocorticoid receptor expression increased up to day 5, before returning progressively to sham values.We observed a striking maintenance of neuronal death associated with enhanced microglial reaction and proliferation, increased YM1 concentration, and decreased TNF-α secretion and glucocorticoid receptor expression.S100B reactivity only increased after astroglia recovery.

View Article: PubMed Central - PubMed

Affiliation: Unitat de Bioquímica i Biologia Molecular, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), C/Casanova 143, 08036 Barcelona, Spain.

ABSTRACT
Brain injury triggers a progressive inflammatory response supported by a dynamic astroglia-microglia interplay. We investigated the progressive chronic features of the astroglia-microglia cross talk in the perspective of neuronal effects in a rat model of hippocampal excitotoxic injury. N-Methyl-D-aspartate (NMDA) injection triggered a process characterized within 38 days by atrophy, neuronal loss, and fast astroglia-mediated S100B increase. Microglia reaction varied with the lesion progression. It presented a peak of tumor necrosis factor-α (TNF-α) secretion at one day after the lesion, and a transient YM1 secretion within the first three days. Microglial glucocorticoid receptor expression increased up to day 5, before returning progressively to sham values. To further investigate the astroglia role in the microglia reaction, we performed concomitant transient astroglia ablation with L-α-aminoadipate and NMDA-induced lesion. We observed a striking maintenance of neuronal death associated with enhanced microglial reaction and proliferation, increased YM1 concentration, and decreased TNF-α secretion and glucocorticoid receptor expression. S100B reactivity only increased after astroglia recovery. Our results argue for an initial neuroprotective microglial reaction, with a direct astroglial control of the microglial cytotoxic response. We propose the recovery of the astroglia-microglia cross talk as a tissue priority conducted to ensure a proper cellular coordination that retails brain damage.

No MeSH data available.


Related in: MedlinePlus