Limits...
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

Timing of the microglial reaction to NMDA in the hippocampus. Photomicrographs illustrate the hippocampal injury and microglial reaction to NMDA-induced lesion at the injection site. Photomicrographs of cresyl-violet stained brain sections of (a) sham rats and (b) NMDA rats 15 days after the lesion. (c) Graph shows the quantification of the area of lesion relative to the whole HF in cresyl-violet stained sections. IB4 histochemistry of sham (PBS) (d) and NMDA rats (e) 15 days after the lesion. (f) Distribution of specific binding sites for [3H]PK-11195 in a coronal rat brain section 15 days after 20 nmol NMDA injection. Note the NMDA-induced increase of specific binding (arrowhead) seen as a white area in the left hippocampus. Graphs show the quantification of the area of microglial reaction in IB4-stained sections (g), the area of enhanced [3H]PK-11195 specific binding (h), and the hippocampal concentration of TNF-α (i) of PBS and NMDA rats during the 38 days of the study. Asterisks in (a), (b), (d), and (e) indicate the injection site. CA1, Cornu Ammonis area 1; DG, dentate gyrus. ∗P < 0.05 different from PBS; #P < 0.05 different from day 0 (LSD post hoc test in (d), (f); KW test in (e)) (n = 6 PBS; n = 6 NMDA rats). Bar: 1 mm in (a), (b), (d), and (e) and 2 mm in (f).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4419226&req=5

fig1: Timing of the microglial reaction to NMDA in the hippocampus. Photomicrographs illustrate the hippocampal injury and microglial reaction to NMDA-induced lesion at the injection site. Photomicrographs of cresyl-violet stained brain sections of (a) sham rats and (b) NMDA rats 15 days after the lesion. (c) Graph shows the quantification of the area of lesion relative to the whole HF in cresyl-violet stained sections. IB4 histochemistry of sham (PBS) (d) and NMDA rats (e) 15 days after the lesion. (f) Distribution of specific binding sites for [3H]PK-11195 in a coronal rat brain section 15 days after 20 nmol NMDA injection. Note the NMDA-induced increase of specific binding (arrowhead) seen as a white area in the left hippocampus. Graphs show the quantification of the area of microglial reaction in IB4-stained sections (g), the area of enhanced [3H]PK-11195 specific binding (h), and the hippocampal concentration of TNF-α (i) of PBS and NMDA rats during the 38 days of the study. Asterisks in (a), (b), (d), and (e) indicate the injection site. CA1, Cornu Ammonis area 1; DG, dentate gyrus. ∗P < 0.05 different from PBS; #P < 0.05 different from day 0 (LSD post hoc test in (d), (f); KW test in (e)) (n = 6 PBS; n = 6 NMDA rats). Bar: 1 mm in (a), (b), (d), and (e) and 2 mm in (f).

Mentions: Observation of Nissl-stained sections revealed that 20 nmol NMDA produced major layer disorganization, neuronal loss, and gliosis in all layers of the hippocampal formation (HF). Animals from the sham group showed no cellular alterations except for the needle scar (Figure 1(a)). The hippocampal lesion extended within 2 mm around the injection site in the rostrocaudal axis, with a slight tendency to grow towards the caudal direction. In the NMDA group (Figure 1(b)), we observed an increase in the area of lesion as a consequence of an initial massive neuronal loss within the first 3 days, followed by a more discrete neuronal death that still progressed at 38 days (Figure 1(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)

Timing of the microglial reaction to NMDA in the hippocampus. Photomicrographs illustrate the hippocampal injury and microglial reaction to NMDA-induced lesion at the injection site. Photomicrographs of cresyl-violet stained brain sections of (a) sham rats and (b) NMDA rats 15 days after the lesion. (c) Graph shows the quantification of the area of lesion relative to the whole HF in cresyl-violet stained sections. IB4 histochemistry of sham (PBS) (d) and NMDA rats (e) 15 days after the lesion. (f) Distribution of specific binding sites for [3H]PK-11195 in a coronal rat brain section 15 days after 20 nmol NMDA injection. Note the NMDA-induced increase of specific binding (arrowhead) seen as a white area in the left hippocampus. Graphs show the quantification of the area of microglial reaction in IB4-stained sections (g), the area of enhanced [3H]PK-11195 specific binding (h), and the hippocampal concentration of TNF-α (i) of PBS and NMDA rats during the 38 days of the study. Asterisks in (a), (b), (d), and (e) indicate the injection site. CA1, Cornu Ammonis area 1; DG, dentate gyrus. ∗P < 0.05 different from PBS; #P < 0.05 different from day 0 (LSD post hoc test in (d), (f); KW test in (e)) (n = 6 PBS; n = 6 NMDA rats). Bar: 1 mm in (a), (b), (d), and (e) and 2 mm in (f).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4419226&req=5

fig1: Timing of the microglial reaction to NMDA in the hippocampus. Photomicrographs illustrate the hippocampal injury and microglial reaction to NMDA-induced lesion at the injection site. Photomicrographs of cresyl-violet stained brain sections of (a) sham rats and (b) NMDA rats 15 days after the lesion. (c) Graph shows the quantification of the area of lesion relative to the whole HF in cresyl-violet stained sections. IB4 histochemistry of sham (PBS) (d) and NMDA rats (e) 15 days after the lesion. (f) Distribution of specific binding sites for [3H]PK-11195 in a coronal rat brain section 15 days after 20 nmol NMDA injection. Note the NMDA-induced increase of specific binding (arrowhead) seen as a white area in the left hippocampus. Graphs show the quantification of the area of microglial reaction in IB4-stained sections (g), the area of enhanced [3H]PK-11195 specific binding (h), and the hippocampal concentration of TNF-α (i) of PBS and NMDA rats during the 38 days of the study. Asterisks in (a), (b), (d), and (e) indicate the injection site. CA1, Cornu Ammonis area 1; DG, dentate gyrus. ∗P < 0.05 different from PBS; #P < 0.05 different from day 0 (LSD post hoc test in (d), (f); KW test in (e)) (n = 6 PBS; n = 6 NMDA rats). Bar: 1 mm in (a), (b), (d), and (e) and 2 mm in (f).
Mentions: Observation of Nissl-stained sections revealed that 20 nmol NMDA produced major layer disorganization, neuronal loss, and gliosis in all layers of the hippocampal formation (HF). Animals from the sham group showed no cellular alterations except for the needle scar (Figure 1(a)). The hippocampal lesion extended within 2 mm around the injection site in the rostrocaudal axis, with a slight tendency to grow towards the caudal direction. In the NMDA group (Figure 1(b)), we observed an increase in the area of lesion as a consequence of an initial massive neuronal loss within the first 3 days, followed by a more discrete neuronal death that still progressed at 38 days (Figure 1(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