Spatial arrangement of microglia in the mouse hippocampus: A stereological study in comparison with astrocytes

Jinno, Shozo; Fleischer, Frank; Eckel, Stefanie; Schmidt, Volker; Kosaka, Toshio

doi:10.1002/glia.20552

Cited by 84 publications

(65 citation statements)

References 54 publications

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“…However, the affinity of P2Y1R is higher for ADP than for ATP (71), allowing for a wider range of efficiency of ATP released from microglia. Microglia display highly ramified processes that are tightly interwoven with astrocytic processes (16). Astrocytes are, therefore, good candidates as intermediates between microglial ATP and synaptic regulation.…”

Section: Discussionmentioning

confidence: 99%

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Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission

Pascual

Achour

Rostaing

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

598

534

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Fine control of neuronal activity is crucial to rapidly adjust to subtle changes of the environment. This fine tuning was thought to be purely neuronal until the discovery that astrocytes are active players of synaptic transmission. In the adult hippocampus, microglia are the other major glial cell type. Microglia are highly dynamic and closely associated with neurons and astrocytes. They react rapidly to modifications of their environment and are able to release molecules known to control neuronal function and synaptic transmission. Therefore, microglia display functional features of synaptic partners, but their involvement in the regulation of synaptic transmission has not yet been addressed. We have used a combination of pharmacological approaches with electrophysiological analysis on acute hippocampal slices and ATP assays in purified cell cultures to show that activation of microglia induces a rapid increase of spontaneous excitatory postsynaptic currents. We found that this modulation is mediated by binding of ATP to P2Y1R located on astrocytes and is independent of TNFα or NOS2. Our data indicate that, on activation, microglia cells rapidly release small amounts of ATP, and astrocytes, in turn, amplified this release. Finally, P2Y1 stimulation of astrocytes increased excitatory postsynaptic current frequency through a metabotropic glutamate receptor 5-dependent mechanism. These results indicate that microglia are genuine regulators of neurotransmission and place microglia as upstream partners of astrocytes. Because pathological activation of microglia and alteration of neurotransmission are two early symptoms of most brain diseases, our work also provides a basis for understanding synaptic dysfunction in neuronal diseases.inflammation | lipopolysaccharide | purine | toll-like receptor 4 | epilepsy

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Section: Discussionmentioning

confidence: 99%

“…Under physiological conditions, microglial cells are present in all regions of the adult brain at rather high density (15). The density of microglia is comparable with the density of astrocytes, and both cell types are closely associated morphologically (16). Microglial cells are highly dynamic and react rapidly to the modification of their environment (17).…”

mentioning

confidence: 99%

Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission

Pascual

Achour

Rostaing

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

598

534

View full text Add to dashboard Cite

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“…The use of such an antibody has recently been reported in the brain or vas deferens of mice (23,27), but, to the best of our knowledge, its application to vascular nerves and to renal tissue is unknown. Validation of such a technical alternative in renal vessels requires further study.…”

Section: Discussionmentioning

confidence: 99%

Topology of Schwann cells and sympathetic innervation along preglomerular vessels: a confocal microscopic study in protein S100B/EGFP transgenic mice

Darlot¹,

Artuso²,

Lautrédou-Audouy³

et al. 2008

American Journal of Physiology-Renal Physiology

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Darlot F, Artuso A, Lautredou-Audouy N, Casellas D. Topology of Schwann cells and sympathetic innervation along preglomerular vessels: a confocal microscopic study in protein S100B/EGFP transgenic mice. Am J Physiol Renal Physiol 295: F1142-F1148, 2008. First published August 20, 2008 doi:10.1152/ajprenal.00599.2007, associated axons, and nearby vascular endothelium constitute a functional trilogy of major importance during the development and regrowth of peripheral vascular nerves. The goal of the present study is to provide a technique of triple fluorescence confocal imaging of these cell types along renal preglomerular vessels. We took advantage of a protein S100B/EGFP transgenic mouse to visualize Sc. The endothelium was labeled with an intravenous injection of fluorescently tagged lectin, and after tissue processing, adrenergic nerves were revealed with an antibody against the marker protein synaptophysin. As a validation step, we found that EGFPpositive perivascular cells with prominent cell bodies and extensive, multidirectional cell processes were protein S100B positive. They were identified as Sc and indirectly assumed to be unmyelinated Sc. By contrast, we found strong EGFP expression in proximal epithelial cells and in the epithelium lining thin limbs of Henle. This epithelial fluorescence was not associated with immunoreactive protein S100B and thus corresponded to ectopic EGFP expressions in this mouse strain. Sc were organized in bundles or as a meshwork surrounding the preglomerular vasculature from arcuate arteries to afferent arterioles. No Sc were detected in the medulla. Although most Sc were closely apposed to adrenergic varicosities, many varicosities were not associated with detectable Sc processes. The present technique, and the capacity of confocal microscopy to yield three-dimensional imaging, allow the study of the microtopology of Sc and related sympathetic axons in the renal perivascular interstitium.immunohistochemistry; triple fluorescence labeling; synaptophysin; Griffonia simplicifolia; isolectin; myelinated and unmyelinated nerves RECENT STUDIES UNDERLINE THE crucial role played by Schwann cells (Sc) in the development and maturation of peripheral sympathetic nerves (5, 21). Functional interactions between Sc and axons are also present during posttraumatic axonal regrowth (5, 7). In this respect, the addition and/or migration of Sc within artificial nerve guides appears as an essential determinant of axonal regrowth (13,26,43). In addition, recent studies establish the existence of common molecular mechanisms that link axonal and vascular guidance during early development (1,31,33,34,38), during posttraumatic axonal regrowth (20), and during tumoral angiogenesis (4, 34). The existence of such a "functional trilogy" among Sc, axons, and vascular endothelial cells gives relevance and importance to the possibility of specifically, and simultaneously, imaging these three cell types in normal and pathological animal models.Transmission electron microscopy (TEM) and immunohistochemist...

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“…They are implemented, for instance, in the GeoStoch Software (Mayer et al 2004) and in the Fspatstat_ package for R (Baddeley & Turner 2005). However, very few attempts have been made to apply such methods to cell biology data (Beil et al 2005, Jinno et al 2007.…”

Section: Clustering Of Genes To Nuclear Bodiesmentioning

confidence: 99%

Spatial quantitative analysis of fluorescently labeled nuclear structures: Problems, methods, pitfalls

et al. 2008

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The vast majority of microscopic data in biology of the cell nucleus is currently collected using fluorescence microscopy, and most of these data are subsequently subjected to quantitative analysis. The analysis process unites a number of steps, from image acquisition to statistics, and at each of these steps decisions must be made that may crucially affect the conclusions of the whole study. This often presents a really serious problem because the researcher is typically a biologist, while the decisions to be taken require expertise in the fields of physics, computer image analysis, and statistics. The researcher has to choose between multiple options for data collection, numerous programs for preprocessing and processing of images, and a number of statistical approaches. Written for biologists, this article discusses some of the typical problems and errors that should be avoided. The article was prepared by a team uniting expertise in biology, microscopy, image analysis, and statistics. It considers the options a researcher has at the stages of data acquisition (choice of the microscope and acquisition settings), preprocessing (filtering, intensity normalization, deconvolution), image processing (radial distribution, clustering, co-localization, shape and orientation of objects), and statistical analysis. Abbreviations

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Spatial arrangement of microglia in the mouse hippocampus: A stereological study in comparison with astrocytes

Cited by 84 publications

References 54 publications

Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission

Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission

Topology of Schwann cells and sympathetic innervation along preglomerular vessels: a confocal microscopic study in protein S100B/EGFP transgenic mice

Spatial quantitative analysis of fluorescently labeled nuclear structures: Problems, methods, pitfalls

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