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Published in: Journal of Neuroinflammation 1/2014

Open Access 01-12-2014 | Research

Quantitative assessment of microglial morphology and density reveals remarkable consistency in the distribution and morphology of cells within the healthy prefrontal cortex of the rat

Authors: Ratchaniporn Kongsui, Sarah B Beynon, Sarah J Johnson, Frederick Rohan Walker

Published in: Journal of Neuroinflammation | Issue 1/2014

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Abstract

Background

Microglial morphology within the healthy brain has been the subject of a number of observational studies. These have suggested that microglia may consist of separate classes, which possess substantially different morphological features. Critically, there have been no systematic quantitative studies of microglial morphology within the healthy brain.

Methods

We examined microglial cells within the adult rat prefrontal cortex. At high magnification, digital reconstructions of cells labelled with the microglial-specific marker ionized calcium-binding adapter molecule-1 (Iba-1) were made in each of the cortical layers. These reconstructions were subsequently analyzed to determine the convex hull area of the cells, their somal perimeter, the length of processes, the number of processes, the extent of process branching and the volume of processes. We additionally examined whether cells’ morphological features were associated with cell size or numerical density.

Results

Our analysis indicated that while there was substantial variability in the size of cells within the prefrontal cortex, cellular morphology was extremely consistent within each of the cortical layers.

Conclusions

Our results provide quantitative confirmation that microglia are largely homogenous in the uninjured rodent prefrontal cortex.
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Literature
1.
go back to reference Streit WJ, Mrak RE, Griffin WS: Microglia and neuroinflammation: a pathological perspective. J Neuroinflammation. 2004, 1 (1): 14-10.1186/1742-2094-1-14.PubMedCentralCrossRefPubMed Streit WJ, Mrak RE, Griffin WS: Microglia and neuroinflammation: a pathological perspective. J Neuroinflammation. 2004, 1 (1): 14-10.1186/1742-2094-1-14.PubMedCentralCrossRefPubMed
2.
go back to reference Yong VW, Rivest S: Taking advantage of the systemic immune system to cure brain diseases. Neuron. 2009, 64 (1): 55-60. 10.1016/j.neuron.2009.09.035.CrossRefPubMed Yong VW, Rivest S: Taking advantage of the systemic immune system to cure brain diseases. Neuron. 2009, 64 (1): 55-60. 10.1016/j.neuron.2009.09.035.CrossRefPubMed
3.
go back to reference Gao HM, Hong JS: Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol. 2008, 29 (8): 357-365. 10.1016/j.it.2008.05.002.CrossRefPubMed Gao HM, Hong JS: Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol. 2008, 29 (8): 357-365. 10.1016/j.it.2008.05.002.CrossRefPubMed
4.
go back to reference Napoli I, Neumann H: Microglial clearance function in health and disease. Neuroscience. 2009, 158 (3): 1030-1038. 10.1016/j.neuroscience.2008.06.046.CrossRefPubMed Napoli I, Neumann H: Microglial clearance function in health and disease. Neuroscience. 2009, 158 (3): 1030-1038. 10.1016/j.neuroscience.2008.06.046.CrossRefPubMed
5.
go back to reference Graeber MB: Changing face of microglia. Science. 2010, 330 (6005): 783-788. 10.1126/science.1190929.CrossRefPubMed Graeber MB: Changing face of microglia. Science. 2010, 330 (6005): 783-788. 10.1126/science.1190929.CrossRefPubMed
6.
go back to reference Ralay Ranaivo H, Craft JM, Hu W, Guo L, Wing LK, Van Eldik LJ, Watterson DM: Glia as a therapeutic target: selective suppression of human amyloid-β-induced upregulation of brain proinflammatory cytokine production attenuates neurodegeneration. J Neurosci. 2006, 26 (2): 662-670. 10.1523/JNEUROSCI.4652-05.2006.CrossRefPubMed Ralay Ranaivo H, Craft JM, Hu W, Guo L, Wing LK, Van Eldik LJ, Watterson DM: Glia as a therapeutic target: selective suppression of human amyloid-β-induced upregulation of brain proinflammatory cytokine production attenuates neurodegeneration. J Neurosci. 2006, 26 (2): 662-670. 10.1523/JNEUROSCI.4652-05.2006.CrossRefPubMed
7.
go back to reference Zlokovic BV: The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008, 57 (2): 178-201. 10.1016/j.neuron.2008.01.003.CrossRefPubMed Zlokovic BV: The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008, 57 (2): 178-201. 10.1016/j.neuron.2008.01.003.CrossRefPubMed
8.
go back to reference Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, Ransohoff RM, Greenberg ME, Barres BA, Stevens B: Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron. 2012, 74 (4): 691-705. 10.1016/j.neuron.2012.03.026.PubMedCentralCrossRefPubMed Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, Ransohoff RM, Greenberg ME, Barres BA, Stevens B: Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron. 2012, 74 (4): 691-705. 10.1016/j.neuron.2012.03.026.PubMedCentralCrossRefPubMed
9.
go back to reference Wake H, Moorhouse AJ, Jinno S, Kohsaka S, Nabekura J: Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci. 2009, 29 (13): 3974-3980. 10.1523/JNEUROSCI.4363-08.2009.CrossRefPubMed Wake H, Moorhouse AJ, Jinno S, Kohsaka S, Nabekura J: Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci. 2009, 29 (13): 3974-3980. 10.1523/JNEUROSCI.4363-08.2009.CrossRefPubMed
10.
go back to reference Tremblay ME, Lowery RL, Majewska AK: Microglial interactions with synapses are modulated by visual experience. PLoS Biol. 2010, 8 (11): e1000527-10.1371/journal.pbio.1000527.PubMedCentralCrossRefPubMed Tremblay ME, Lowery RL, Majewska AK: Microglial interactions with synapses are modulated by visual experience. PLoS Biol. 2010, 8 (11): e1000527-10.1371/journal.pbio.1000527.PubMedCentralCrossRefPubMed
11.
go back to reference Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB: ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci. 2005, 8 (6): 752-758. 10.1038/nn1472.CrossRefPubMed Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB: ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci. 2005, 8 (6): 752-758. 10.1038/nn1472.CrossRefPubMed
12.
go back to reference Nimmerjahn A, Kirchhoff F, Helmchen F: Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science. 2005, 308 (5726): 1314-1318. 10.1126/science.1110647.CrossRefPubMed Nimmerjahn A, Kirchhoff F, Helmchen F: Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science. 2005, 308 (5726): 1314-1318. 10.1126/science.1110647.CrossRefPubMed
13.
go back to reference Raivich G: Like cops on the beat: the active role of resting microglia. Trends Neurosci. 2005, 28 (11): 571-573. 10.1016/j.tins.2005.09.001.CrossRefPubMed Raivich G: Like cops on the beat: the active role of resting microglia. Trends Neurosci. 2005, 28 (11): 571-573. 10.1016/j.tins.2005.09.001.CrossRefPubMed
14.
go back to reference Hinwood M, Tynan RJ, Charnley JL, Beynon SB, Day TA, Walker FR: Chronic stress induced remodeling of the prefrontal cortex: structural re-organization of microglia and the inhibitory effect of minocycline. Cereb Cortex. 2012, 23: 1784-1797. 10.1093/cercor/bhs151.CrossRefPubMed Hinwood M, Tynan RJ, Charnley JL, Beynon SB, Day TA, Walker FR: Chronic stress induced remodeling of the prefrontal cortex: structural re-organization of microglia and the inhibitory effect of minocycline. Cereb Cortex. 2012, 23: 1784-1797. 10.1093/cercor/bhs151.CrossRefPubMed
15.
go back to reference Walker FR, Beynon SB, Jones KA, Zhao Z, Kongsui R, Cairns M, Nilsson M: Dynamic structural remodelling of microglia in health and disease: a review of the models, the signals and the mechanisms. Brain Behav Immun. 2014, 37: 1-14. 10.1016/j.bbi.2013.12.010.CrossRefPubMed Walker FR, Beynon SB, Jones KA, Zhao Z, Kongsui R, Cairns M, Nilsson M: Dynamic structural remodelling of microglia in health and disease: a review of the models, the signals and the mechanisms. Brain Behav Immun. 2014, 37: 1-14. 10.1016/j.bbi.2013.12.010.CrossRefPubMed
16.
go back to reference Lawson LJ, Perry VH, Dri P, Gordon S: Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience. 1990, 39 (1): 151-170. 10.1016/0306-4522(90)90229-W.CrossRefPubMed Lawson LJ, Perry VH, Dri P, Gordon S: Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience. 1990, 39 (1): 151-170. 10.1016/0306-4522(90)90229-W.CrossRefPubMed
17.
go back to reference Vela JM, Dalmau I, Gonzalez B, Castellano B: Morphology and distribution of microglial cells in the young and adult mouse cerebellum. J Comp Neurol. 1995, 361 (4): 602-616. 10.1002/cne.903610405.CrossRefPubMed Vela JM, Dalmau I, Gonzalez B, Castellano B: Morphology and distribution of microglial cells in the young and adult mouse cerebellum. J Comp Neurol. 1995, 361 (4): 602-616. 10.1002/cne.903610405.CrossRefPubMed
18.
go back to reference Jinno S, Fleischer F, Eckel S, Schmidt V, Kosaka T: Spatial arrangement of microglia in the mouse hippocampus: a stereological study in comparison with astrocytes. Glia. 2007, 55 (13): 1334-1347. 10.1002/glia.20552.CrossRefPubMed Jinno S, Fleischer F, Eckel S, Schmidt V, Kosaka T: Spatial arrangement of microglia in the mouse hippocampus: a stereological study in comparison with astrocytes. Glia. 2007, 55 (13): 1334-1347. 10.1002/glia.20552.CrossRefPubMed
19.
go back to reference Yamada J, Jinno S: Novel objective classification of reactive microglia following hypoglossal axotomy using hierarchical cluster analysis. J Comp Neurol. 2012, 521: 1184-1201. 10.1002/cne.23228.CrossRef Yamada J, Jinno S: Novel objective classification of reactive microglia following hypoglossal axotomy using hierarchical cluster analysis. J Comp Neurol. 2012, 521: 1184-1201. 10.1002/cne.23228.CrossRef
20.
go back to reference Torres-Platas SG, Comeau S, Rachalski A, Bo GD, Cruceanu C, Turecki G, Giros B, Mechawar N: Morphometric characterization of microglial phenotypes in human cerebral cortex. J Neuroinflammation. 2014, 11: 12-10.1186/1742-2094-11-12.PubMedCentralCrossRefPubMed Torres-Platas SG, Comeau S, Rachalski A, Bo GD, Cruceanu C, Turecki G, Giros B, Mechawar N: Morphometric characterization of microglial phenotypes in human cerebral cortex. J Neuroinflammation. 2014, 11: 12-10.1186/1742-2094-11-12.PubMedCentralCrossRefPubMed
21.
go back to reference Sasaki Y, Ohsawa K, Kanazawa H, Kohsaka S, Imai Y: Iba1 is an actin-cross-linking protein in macrophages/microglia. Biochem Biophys Res Commun. 2001, 286 (2): 292-297. 10.1006/bbrc.2001.5388.CrossRefPubMed Sasaki Y, Ohsawa K, Kanazawa H, Kohsaka S, Imai Y: Iba1 is an actin-cross-linking protein in macrophages/microglia. Biochem Biophys Res Commun. 2001, 286 (2): 292-297. 10.1006/bbrc.2001.5388.CrossRefPubMed
22.
go back to reference Kondo S, Kohsaka S, Okabe S: Long-term changes of spine dynamics and microglia after transient peripheral immune response triggered by LPS in vivo. Molecular Brain. 2011, 4: 27-10.1186/1756-6606-4-27.PubMedCentralCrossRefPubMed Kondo S, Kohsaka S, Okabe S: Long-term changes of spine dynamics and microglia after transient peripheral immune response triggered by LPS in vivo. Molecular Brain. 2011, 4: 27-10.1186/1756-6606-4-27.PubMedCentralCrossRefPubMed
23.
go back to reference Tynan RJ, Naicker S, Hinwood M, Nalivaiko E, Buller KM, Pow DV, Day TA, Walker FR: Chronic stress alters the density and morphology of microglia in a subset of stress-responsive brain regions. Brain Behav Immun. 2010, 24 (7): 1058-1068. 10.1016/j.bbi.2010.02.001.CrossRefPubMed Tynan RJ, Naicker S, Hinwood M, Nalivaiko E, Buller KM, Pow DV, Day TA, Walker FR: Chronic stress alters the density and morphology of microglia in a subset of stress-responsive brain regions. Brain Behav Immun. 2010, 24 (7): 1058-1068. 10.1016/j.bbi.2010.02.001.CrossRefPubMed
24.
go back to reference Hinwood M, Morandini J, Day TA, Walker FR: Evidence that microglia mediate the neurobiological effects of chronic psychological stress on the medial prefrontal cortex. Cereb Cortex. 2012, 22 (6): 1442-1454. 10.1093/cercor/bhr229.CrossRefPubMed Hinwood M, Morandini J, Day TA, Walker FR: Evidence that microglia mediate the neurobiological effects of chronic psychological stress on the medial prefrontal cortex. Cereb Cortex. 2012, 22 (6): 1442-1454. 10.1093/cercor/bhr229.CrossRefPubMed
25.
go back to reference Paxinos G, Watson C: The Rat Brain in Stereotaxic Coordinates. 1998, Academic Press, San Diego, California Paxinos G, Watson C: The Rat Brain in Stereotaxic Coordinates. 1998, Academic Press, San Diego, California
26.
go back to reference Morshedi MM, Meredith GE: Differential laminar effects of amphetamine on prefrontal parvalbumin interneurons. Neuroscience. 2007, 149 (3): 617-624. 10.1016/j.neuroscience.2007.07.047.PubMedCentralCrossRefPubMed Morshedi MM, Meredith GE: Differential laminar effects of amphetamine on prefrontal parvalbumin interneurons. Neuroscience. 2007, 149 (3): 617-624. 10.1016/j.neuroscience.2007.07.047.PubMedCentralCrossRefPubMed
27.
go back to reference Gabbott PL, Warner TA, Jays PR, Salway P, Busby SJ: Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers. J Comp Neurol. 2005, 492 (2): 145-177. 10.1002/cne.20738.CrossRefPubMed Gabbott PL, Warner TA, Jays PR, Salway P, Busby SJ: Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers. J Comp Neurol. 2005, 492 (2): 145-177. 10.1002/cne.20738.CrossRefPubMed
28.
go back to reference Fernandez E, Jelinek HF: Use of fractal theory in neuroscience: methods, advantages, and potential problems. Methods. 2001, 24 (4): 309-321. 10.1006/meth.2001.1201.CrossRefPubMed Fernandez E, Jelinek HF: Use of fractal theory in neuroscience: methods, advantages, and potential problems. Methods. 2001, 24 (4): 309-321. 10.1006/meth.2001.1201.CrossRefPubMed
29.
go back to reference Sholl DA: The measurable parameters of the cerebral cortex and their significance in its organization. Prog Neurobiol. 1956, 2: 324-333.PubMed Sholl DA: The measurable parameters of the cerebral cortex and their significance in its organization. Prog Neurobiol. 1956, 2: 324-333.PubMed
30.
go back to reference Beynon SB, Walker FR: Microglial activation in the injured and healthy brain: what are we really talking about? Practical and theoretical issues associated with the measurement of changes in microglial morphology. Neuroscience. 2012, 225: 162-171. 10.1016/j.neuroscience.2012.07.029.CrossRefPubMed Beynon SB, Walker FR: Microglial activation in the injured and healthy brain: what are we really talking about? Practical and theoretical issues associated with the measurement of changes in microglial morphology. Neuroscience. 2012, 225: 162-171. 10.1016/j.neuroscience.2012.07.029.CrossRefPubMed
31.
go back to reference Yamada J, Nakanishi H, Jinno S: Differential involvement of perineuronal astrocytes and microglia in synaptic stripping after hypoglossal axotomy. Neuroscience. 2011, 182: 1-10. 10.1016/j.neuroscience.2011.03.030.CrossRefPubMed Yamada J, Nakanishi H, Jinno S: Differential involvement of perineuronal astrocytes and microglia in synaptic stripping after hypoglossal axotomy. Neuroscience. 2011, 182: 1-10. 10.1016/j.neuroscience.2011.03.030.CrossRefPubMed
32.
go back to reference Herculano-Houzel S, Mota B, Lent R: Cellular scaling rules for rodent brains. Proc Natl Acad Sci USA. 2006, 103 (32): 12138-12143. 10.1073/pnas.0604911103.PubMedCentralCrossRefPubMed Herculano-Houzel S, Mota B, Lent R: Cellular scaling rules for rodent brains. Proc Natl Acad Sci USA. 2006, 103 (32): 12138-12143. 10.1073/pnas.0604911103.PubMedCentralCrossRefPubMed
33.
go back to reference Cotter DR, Pariante CM, Everall IP: Glial cell abnormalities in major psychiatric disorders: the evidence and implications. Brain Res Bull. 2001, 55 (5): 585-595. 10.1016/S0361-9230(01)00527-5.CrossRefPubMed Cotter DR, Pariante CM, Everall IP: Glial cell abnormalities in major psychiatric disorders: the evidence and implications. Brain Res Bull. 2001, 55 (5): 585-595. 10.1016/S0361-9230(01)00527-5.CrossRefPubMed
34.
go back to reference Eyre H, Baune BT: Neuroplastic changes in depression: a role for the immune system. Psychoneuroendocrinology. 2012, 37: 1397-1416. 10.1016/j.psyneuen.2012.03.019.CrossRefPubMed Eyre H, Baune BT: Neuroplastic changes in depression: a role for the immune system. Psychoneuroendocrinology. 2012, 37: 1397-1416. 10.1016/j.psyneuen.2012.03.019.CrossRefPubMed
Metadata
Title
Quantitative assessment of microglial morphology and density reveals remarkable consistency in the distribution and morphology of cells within the healthy prefrontal cortex of the rat
Authors
Ratchaniporn Kongsui
Sarah B Beynon
Sarah J Johnson
Frederick Rohan Walker
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2014
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-014-0182-7

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