| Journal of Neuroinflammation | |
| Altered morphological dynamics of activated microglia after induction of status epilepticus | |
| U. Valentin Nägerl1  Julie Angibaud1  Marilyn Lepleux1  Elena Avignone1  | |
| [1] Université de Bordeaux, CNRS UMR 5297, Bordeaux, 33077, France | |
| 关键词: Laser lesion; Two-photon microscopy; Inflammation; Epilepsy; Microglial dynamics; Microglia; | |
| Others : 1230484 DOI : 10.1186/s12974-015-0421-6 |
|
| received in 2015-06-15, accepted in 2015-10-26, 发布年份 2015 | |
【 摘 要 】
Background
Microglia cells are the resident macrophages of the central nervous system and are considered its first line of defense. In the normal brain, their ramified processes are highly motile, constantly scanning the surrounding brain tissue and rapidly moving towards sites of acute injury or danger signals. These microglial dynamics are thought to be critical for brain homeostasis. Under pathological conditions, microglial cells undergo “activation,” which modifies many of their molecular and morphological properties. Investigations of the effects of activation on motility are limited and have given mixed results. In particular, little is known about how microglial motility is altered in epilepsy, which is characterized by a strong inflammatory reaction and microglial activation.
Methods
We used a mouse model of status epilepticus induced by kainate injections and time-lapse two-photon microscopy to image GFP-labeled microglia in acute hippocampal brain slices. We studied how microglial activation affected the motility of microglial processes, including basal motility, and their responses to local triggering stimuli.
Results
Our study reveals that microglial motility was largely preserved in kainate-treated animals, despite clear signs of microglial activation. In addition, whereas the velocities of microglial processes during basal scanning and towards a laser lesion were unaltered 48 h after status epilepticus, we observed an increase in the size of the territory scanned by single microglial processes during basal motility and an elevated directional velocity towards a pipette containing a purinergic agonist.
Conclusions
Microglial activation differentially impacted the dynamic scanning behavior of microglia in response to specific acute noxious stimuli, which may be an important feature of the adaptive behavior of microglia during pathophysiological conditions.
【 授权许可】
2015 Avignone et al.
| Files | Size | Format | View |
|---|---|---|---|
| Fig. 4. | 92KB | Image | |
| Fig. 3. | 66KB | Image | |
| Fig. 2. | 71KB | Image | |
| Fig. 1. | 106KB | Image | |
| Fig. 4. | 92KB | Image | |
| Fig. 3. | 66KB | Image | |
| Fig. 2. | 71KB | Image | |
| Fig. 1. | 106KB | Image |
【 图 表 】
Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
【 参考文献 】
- [1]Kettenmann H, Hanisch U-K, Noda M, Verkhratsky A: Physiology of microglia. Physiol Rev 2011, 91:461-553.
- [2]Kettenmann H, Kirchhoff F, Verkhratsky A: Microglia: new roles for the synaptic stripper. Neuron 2013, 77:10-18.
- [3]Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, et al.: ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 2005, 8:752-758.
- [4]Nimmerjahn A, Kirchhoff F, Helmchen F: Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 2005, 308:1314-1318.
- [5]Parkhurst CN, Gan W-B: Microglia dynamics and function in the CNS. Curr Opin Neurobiol 2010, 20:595-600.
- [6]Madry C, Attwell D: Receptors, ion channels, and signaling mechanisms underlying microglial dynamics. J Biol Chem 2015, 290:12443-12450.
- [7]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 Off J Soc Neurosci 2009, 29:3974-3980.
- [8]Tremblay M-È, Lowery RL, Majewska AK: Microglial interactions with synapses are modulated by visual experience. PLoS Biol 2010., 8Article ID e1000527
- [9]Dibaj P, Nadrigny F, Steffens H, Scheller A, Hirrlinger J, Schomburg ED, et al.: NO mediates microglial response to acute spinal cord injury under ATP control in vivo. Glia 2010, 58:1133-1144.
- [10]Hines DJ, Hines RM, Mulligan SJ, Macvicar BA: Microglia processes block the spread of damage in the brain and require functional chloride channels. Glia 2009, 57:1610-1618.
- [11]Domercq M, Vázquez-Villoldo N, Matute C: Neurotransmitter signaling in the pathophysiology of microglia. Front Cell Neurosci 2013, 7:49.
- [12]Fontainhas AM, Wang M, Liang KJ, Chen S, Mettu P, Damani M, et al.: Microglial morphology and dynamic behavior is regulated by ionotropic glutamatergic and GABAergic neurotransmission. PLoS One 2011., 6Article ID e15973
- [13]Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan W-B, et al.: The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 2006, 9:1512-1519.
- [14]Sieger D, Moritz C, Ziegenhals T, Prykhozhij S, Peri F: Long-range Ca2+ waves transmit brain-damage signals to microglia. Dev Cell 2012, 22:1138-1148.
- [15]Hanisch U-K, Kettenmann H: Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 2007, 10:1387-1394.
- [16]Ransohoff RM, Perry VH: Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol 2009, 27:119-145.
- [17]Vezzani A, Aronica E, Mazarati A, Pittman QJ: Epilepsy and brain inflammation. Exp Neurol 2013, 244:11-21.
- [18]Avignone E, Ulmann L, Levavasseur F, Rassendren F, Audinat E: Status epilepticus induces a particular microglial activation state characterized by enhanced purinergic signaling. J Neurosci Off J Soc Neurosci 2008, 28:9133-9144.
- [19]Ulmann L, Levavasseur F, Avignone E, Peyroutou R, Hirbec H, Audinat E, et al.: Involvement of P2X4 receptors in hippocampal microglial activation after status epilepticus. Glia 2013, 61:1306-1319.
- [20]Jimenez-Pacheco A, Mesuret G, Sanz-Rodriguez A, Tanaka K, Mooney C, Conroy R, et al.: Increased neocortical expression of the P2X7 receptor after status epilepticus and anticonvulsant effect of P2X7 receptor antagonist A-438079. Epilepsia 2013, 54:1551-1561.
- [21]Eyo UB, Peng J, Swiatkowski P, Mukherjee A, Bispo A, Wu L-J: Neuronal hyperactivity recruits microglial processes via neuronal NMDA receptors and microglial P2Y12 receptors after status epilepticus. J Neurosci Off J Soc Neurosci 2014, 34:10528-10540.
- [22]Thévenaz P, Ruttimann UE, Unser M: A pyramid approach to subpixel registration based on intensity. IEEE Trans Image Process Publ IEEE Signal Process Soc 1998, 7:27-41.
- [23]Meijering E, Dzyubachyk O, Smal I: Methods for cell and particle tracking. Methods Enzymol 2012, 504:183-200.
- [24]Kozlowski C, Weimer RM: An automated method to quantify microglia morphology and application to monitor activation state longitudinally in vivo. PLoS One 2012., 7Article ID e31814
- [25]Papageorgiou IE, Fetani AF, Lewen A, Heinemann U, Kann O: Widespread activation of microglial cells in the hippocampus of chronic epileptic rats correlates only partially with neurodegeneration. Brain Struct Funct 2015, 220:2423-2439.
- [26]Shapiro LA, Wang L, Ribak CE: Rapid astrocyte and microglial activation following pilocarpine-induced seizures in rats. Epilepsia 2008, 49(Suppl 2):33-41.
- [27]Morrison HW, Filosa JA: A quantitative spatiotemporal analysis of microglia morphology during ischemic stroke and reperfusion. J Neuroinflammation 2013, 10:4. BioMed Central Full Text
- [28]Wu LJ, Vadakkan KI, Zhuo M: ATP-induced chemotaxis of microglial processes requires P2Y receptor-activated initiation of outward potassium currents. Glia 2007, 55:810-821.
- [29]Ridley AJ: Life at the leading edge. Cell 2011, 145:1012-1022.
- [30]Sadok A, Marshall CJ: Rho GTPases: masters of cell migration. Small GTPases 2014., 5Article ID e29710
- [31]Murali A, Rajalingam K: Small Rho GTPases in the control of cell shape and mobility. Cell Mol Life Sci CMLS 2014, 71:1703-1721.
- [32]Soulet C, Hechler B, Gratacap M-P, Plantavid M, Offermanns S, Gachet C, et al.: A differential role of the platelet ADP receptors P2Y1 and P2Y12 in Rac activation. J Thromb Haemost JTH 2005, 3:2296-2306.
- [33]Erb L, Weisman GA: Coupling of P2Y receptors to G proteins and other signaling pathways. Wiley Interdiscip Rev Membr Transp Signal 2012, 1:789-803.
- [34]Dibaj P, Steffens H, Zschüntzsch J, Nadrigny F, Schomburg ED, Kirchhoff F, et al.: In vivo imaging reveals distinct inflammatory activity of CNS microglia versus PNS macrophages in a mouse model for ALS. PLoS One 2011., 6Article ID e17910
- [35]Brawek B, Schwendele B, Riester K, Kohsaka S, Lerdkrai C, Liang Y, et al.: Impairment of in vivo calcium signaling in amyloid plaque-associated microglia. Acta Neuropathol (Berl) 2014, 127:495-505.
- [36]Krabbe G, Halle A, Matyash V, Rinnenthal JL, Eom GD, Bernhardt U, et al.: Functional impairment of microglia coincides with beta-amyloid deposition in mice with Alzheimer-like pathology. PLoS One 2013., 8Article ID e60921
- [37]Bolmont T, Haiss F, Eicke D, Radde R, Mathis CA, Klunk WE, et al.: Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance. J Neurosci Off J Soc Neurosci 2008, 28:4283-4292.
- [38]Kondo S, Kohsaka S, Okabe S: Long-term changes of spine dynamics and microglia after transient peripheral immune response triggered by LPS in vivo. Mol Brain 2011, 4:27. BioMed Central Full Text
- [39]Madore C, Joffre C, Delpech JC, De Smedt-Peyrusse V, Aubert A, Coste L, et al.: Early morphofunctional plasticity of microglia in response to acute lipopolysaccharide. Brain Behav Immun 2013, 34:151-158.
- [40]Gyoneva S, Davalos D, Biswas D, Swanger SA, Garnier-Amblard E, Loth F, et al.: Systemic inflammation regulates microglial responses to tissue damage in vivo. Glia 2014, 62:1345-1360.
- [41]Uhlemann R, Gertz K, Boehmerle W, Schwarz T, Nolte C, Freyer D, et al. Actin dynamics shape microglia effector functions. Brain Struct Funct. 2015.
- [42]Kobayashi K, Yamanaka H, Fukuoka T, Dai Y, Obata K, Noguchi K: P2Y12 receptor upregulation in activated microglia is a gateway of p38 signaling and neuropathic pain. J Neurosci Off J Soc Neurosci 2008, 28:2892-2902.
- [43]Moore CS, Ase AR, Kinsara A, Rao VTS, Michell-Robinson M, Leong SY, et al.: P2Y12 expression and function in alternatively activated human microglia. Neurol Neuroimmunol Neuroinflammation 2015., 2Article ID e80
- [44]Amadio S, Montilli C, Magliozzi R, Bernardi G, Reynolds R, Volonté C: P2Y12 receptor protein in cortical gray matter lesions in multiple sclerosis. Cereb Cortex 2010, 20:1263-1273.
- [45]Amadio S, Parisi C, Montilli C, Carrubba AS, Apolloni S, Volonté C: P2Y(12) receptor on the verge of a neuroinflammatory breakdown. Mediators Inflamm 2014, 2014:975849.