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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 astroglial reaction in the hippocampus. GFAP-immunostaining 1 (a) and 3 days (b) in sham animals, 1 (c) and 3 days (d) after α-AA, 1 (e) and 3 days (f) after NMDA lesion, and 1 (g) and 3 days (h) after α-AA + NMDA injection (arrowheads show the injection site). Please note in (c) and (g) the lack of GFAP-immunopositive cells in the surroundings of the injection site. Graphs show the quantification of the area of astrogliosis in the whole hippocampus. (i) GFAP-immunostained and S100B-immunostained (j) sections of sham (PBS), α-AA, NMDA, and α-AA + NMDA rats at postlesion days 1, 3, 15, and 38. (k) Graph shows the estimation of the ratio S100B/GFAP, calculated as the quotient between the area of increased S100B and the area of increased GFAP in these rats. Photomicrographs illustrate GFAP-immunoreactive cells of NMDA (l) and α-AA + NMDA (m) rats and S100B-immunoreactive cells of MNDA (n) and α-AA + NMDA (o) rats in the hippocampal parenchyma 3 days after the lesion. ∗P < 0.05 different from PBS; #P < 0.05 different from NMDA; $P < 0.05 different from day 15 (LSD post hoc test) (n = 6 rats/group). Bar: 1 mm in (a)–(h) and 10 μm in (l)–(o).
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fig4: α-AA effect on the NMDA-induced astroglial reaction in the hippocampus. GFAP-immunostaining 1 (a) and 3 days (b) in sham animals, 1 (c) and 3 days (d) after α-AA, 1 (e) and 3 days (f) after NMDA lesion, and 1 (g) and 3 days (h) after α-AA + NMDA injection (arrowheads show the injection site). Please note in (c) and (g) the lack of GFAP-immunopositive cells in the surroundings of the injection site. Graphs show the quantification of the area of astrogliosis in the whole hippocampus. (i) GFAP-immunostained and S100B-immunostained (j) sections of sham (PBS), α-AA, NMDA, and α-AA + NMDA rats at postlesion days 1, 3, 15, and 38. (k) Graph shows the estimation of the ratio S100B/GFAP, calculated as the quotient between the area of increased S100B and the area of increased GFAP in these rats. Photomicrographs illustrate GFAP-immunoreactive cells of NMDA (l) and α-AA + NMDA (m) rats and S100B-immunoreactive cells of MNDA (n) and α-AA + NMDA (o) rats in the hippocampal parenchyma 3 days after the lesion. ∗P < 0.05 different from PBS; #P < 0.05 different from NMDA; $P < 0.05 different from day 15 (LSD post hoc test) (n = 6 rats/group). Bar: 1 mm in (a)–(h) and 10 μm in (l)–(o).

Mentions: The treatment only with α-AA induced a loss in the GFAP-immunoreactivity (IR) in a small area of the hippocampus around the injection site that was already recovered at day 3 after injection (Figures 4(a)–4(d)). In the NMDA group, the GFAP-IR increase was maximal at day 13 (Figures 4(c) and 4(d)) and then progressively decreased by day 38. In the α-AA + NMDA group only a few astrocytes showed a weak reactive morphology at day 1 (Figures 4(e)–4(h)). At day 3, the area of enhanced GFAP-IR covered 29 ± 7% of the HF (Figure 4(i)), which increased slightly by day 38 to reach similar values to those obtained in the NMDA group at this time point. At day 38, reactive hippocampal astrocytes of α-AA + NMDA rats presented enhanced hypertrophy and hyperplasia and stronger GFAP-IR than did those of the NMDA group (Figures 4(l) and 4(m)).


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 astroglial reaction in the hippocampus. GFAP-immunostaining 1 (a) and 3 days (b) in sham animals, 1 (c) and 3 days (d) after α-AA, 1 (e) and 3 days (f) after NMDA lesion, and 1 (g) and 3 days (h) after α-AA + NMDA injection (arrowheads show the injection site). Please note in (c) and (g) the lack of GFAP-immunopositive cells in the surroundings of the injection site. Graphs show the quantification of the area of astrogliosis in the whole hippocampus. (i) GFAP-immunostained and S100B-immunostained (j) sections of sham (PBS), α-AA, NMDA, and α-AA + NMDA rats at postlesion days 1, 3, 15, and 38. (k) Graph shows the estimation of the ratio S100B/GFAP, calculated as the quotient between the area of increased S100B and the area of increased GFAP in these rats. Photomicrographs illustrate GFAP-immunoreactive cells of NMDA (l) and α-AA + NMDA (m) rats and S100B-immunoreactive cells of MNDA (n) and α-AA + NMDA (o) rats in the hippocampal parenchyma 3 days after the lesion. ∗P < 0.05 different from PBS; #P < 0.05 different from NMDA; $P < 0.05 different from day 15 (LSD post hoc test) (n = 6 rats/group). Bar: 1 mm in (a)–(h) and 10 μm in (l)–(o).
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Related In: Results  -  Collection

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fig4: α-AA effect on the NMDA-induced astroglial reaction in the hippocampus. GFAP-immunostaining 1 (a) and 3 days (b) in sham animals, 1 (c) and 3 days (d) after α-AA, 1 (e) and 3 days (f) after NMDA lesion, and 1 (g) and 3 days (h) after α-AA + NMDA injection (arrowheads show the injection site). Please note in (c) and (g) the lack of GFAP-immunopositive cells in the surroundings of the injection site. Graphs show the quantification of the area of astrogliosis in the whole hippocampus. (i) GFAP-immunostained and S100B-immunostained (j) sections of sham (PBS), α-AA, NMDA, and α-AA + NMDA rats at postlesion days 1, 3, 15, and 38. (k) Graph shows the estimation of the ratio S100B/GFAP, calculated as the quotient between the area of increased S100B and the area of increased GFAP in these rats. Photomicrographs illustrate GFAP-immunoreactive cells of NMDA (l) and α-AA + NMDA (m) rats and S100B-immunoreactive cells of MNDA (n) and α-AA + NMDA (o) rats in the hippocampal parenchyma 3 days after the lesion. ∗P < 0.05 different from PBS; #P < 0.05 different from NMDA; $P < 0.05 different from day 15 (LSD post hoc test) (n = 6 rats/group). Bar: 1 mm in (a)–(h) and 10 μm in (l)–(o).
Mentions: The treatment only with α-AA induced a loss in the GFAP-immunoreactivity (IR) in a small area of the hippocampus around the injection site that was already recovered at day 3 after injection (Figures 4(a)–4(d)). In the NMDA group, the GFAP-IR increase was maximal at day 13 (Figures 4(c) and 4(d)) and then progressively decreased by day 38. In the α-AA + NMDA group only a few astrocytes showed a weak reactive morphology at day 1 (Figures 4(e)–4(h)). At day 3, the area of enhanced GFAP-IR covered 29 ± 7% of the HF (Figure 4(i)), which increased slightly by day 38 to reach similar values to those obtained in the NMDA group at this time point. At day 38, reactive hippocampal astrocytes of α-AA + NMDA rats presented enhanced hypertrophy and hyperplasia and stronger GFAP-IR than did those of the NMDA group (Figures 4(l) and 4(m)).

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