Microglia and synapse: Interactions in health and neurodegeneration

Neural Plasticity

Volumn 2013, Issue , 2013, Pages

  Šišková, Zuzana ^a   Tremblay, Marie Ève ^b  

^a GERMAN CENTER FOR NEURODEGENERATIVE DISEASES DZNE   (Germany)

^b Université Laval   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ALZHEIMER DISEASE; CEREBROVASCULAR ACCIDENT; DENDRITIC SPINE; HUMAN; MICROGLIA; NERVE DEGENERATION; NERVE FUNCTION; NONHUMAN; PHAGOCYTOSIS; PRION DISEASE; REVIEW; SYNAPSE; ANIMAL; DEGENERATIVE DISEASE; HEALTH; PATHOLOGY; PHYSIOLOGY;

ALZHEIMER DISEASE; ANIMALS; HEALTH; HUMANS; MICROGLIA; NEURODEGENERATIVE DISEASES; PRION DISEASES; SYNAPSES;

EID: 84893854992     PISSN: 20905904     EISSN: 16875443     Source Type: Journal    
DOI: 10.1155/2013/425845     Document Type: Review

References (96)

1. Ginhoux F., Greter M., Leboeuf M., Nandi S., See P., Gokhan S., Mehler M. F., Conway S. J., Ng L. G., Stanley E. R., Samokhvalov I. M., Merad M., Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 2010 330 6005 841 845 2-s2.0-78149360132 10.1126/science.1194637
2. Ginhoux F., Lim S., Hoeffel G., Low D., Huber T., Origin and differentiation of microglia. Frontiers in Cellular Neuroscience 2013 7, article 45 10.3389/fncel.2013.00045
3. Kierdorf K., Erny D., Goldmann T., Sander V., Schulz C., Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nature Neuroscience 2013 16 273 280 10.1038/nn.3318
4. Davalos D., Grutzendler J., Yang G., Kim J. V., Zuo Y., Jung S., Littman D. R., Dustin M. L., Gan W.-B., ATP mediates rapid microglial response to local brain injury in vivo. Nature Neuroscience 2005 8 6 752 758 2-s2.0-22244464662 10.1038/nn1472 (Pubitemid 43085841)
5. Nimmerjahn A., Kirchhoff F., Helmchen F., Neuroscience: resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 2005 308 5726 1314 1318 2-s2.0-19744380563 10.1126/science.1110647 (Pubitemid 40746128)
6. Fontainhas A. M., Wang M., Liang K. J., Chen S., Mettu P., Damani M., Fariss R. N., Li W., Wong W. T., Microglial morphology and dynamic behavior is regulated by ionotropic glutamatergic and GABAergic neurotransmission. PLoS ONE 2011 6 1 2-s2.0-79551570269 10.1371/journal.pone.0015973 e15973
7. Eyo U. B., Dailey M. E., Microglia: key elements in neural development, plasticity, and pathology. Journal of Neuroimmune Pharmacology 2013 8 3 494 509 10.1007/s11481-013-9434-z
8. Dibaj P., Nadrigny F., Steffens H., Scheller A., Hirrlinger J., Schomburg E. D., Neusch C., Kirchhoff F., NO mediates microglial response to acute spinal cord injury under ATP control in vivo. Glia 2010 58 9 1133 1144 2-s2.0-77954398133 10.1002/glia.20993
9. Kreutzberg G. W., Microglia: a sensor for pathological events in the CNS. Trends in Neurosciences 1996 19 8 312 318 2-s2.0-0030222037 10.1016/0166-2236(96)10049-7 (Pubitemid 26349059)
10. Hanisch U.-K., Kettenmann H., Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nature Neuroscience 2007 10 11 1387 1394 2-s2.0-35548986304 10.1038/nn1997 (Pubitemid 350014685)
11. Ransohoff R. M., Perry V. H., Microglial physiology: unique stimuli, specialized responses. Annual Review of Immunology 2009 27 119 145 2-s2.0-67650966680 10.1146/annurev.immunol.021908.132528
12. Helmut K., Hanisch U.-K., Noda M., Verkhratsky A., Physiology of microglia. Physiological Reviews 2011 91 2 461 553 2-s2.0-79955605102 10.1152/physrev.00011.2010
13. Bessis A., Béchade C., Bernard D., Roumier A., Microglial control of neuronal death and synaptic properties. Glia 2007 55 3 233 238 2-s2.0-33846887598 10.1002/glia.20459 (Pubitemid 46225955)
14. Neher J. J., Neniskyte U., Brown G. C., Primary phagocytosis of neurons by inflamed microglia: potential roles in neurodegeneration. Frontiers in Pharmacology 2012 3, article 27 10.3389/fphar.2012.00027
15. Prinz M., Priller J., Sisodia S. S., Ransohoff R. M., Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nature Neuroscience 2011 14 10 1227 1235 2-s2.0-80053233055 10.1038/nn.2923
16. Trapp B. D., Wujek J. R., Criste G. A., Jalabi W., Yin X., Kidd G. J., Stohlman S., Ransohoff R., Evidence for synaptic stripping by cortical microglia. Glia 2007 55 4 360 368 2-s2.0-33846953580 10.1002/glia.20462
17. Blinzinger K., Kreutzberg G., Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Zeitschrift für Zellforschung und Mikroskopische Anatomie 1968 85 2 145 157 2-s2.0-0014369295 10.1007/BF00325030
18. Tremblay M.-È., The role of microglia at synapses in the healthy CNS: novel insights from recent imaging studies. Neuron Glia Biology 2011 7 67 76 10.1017/S1740925X12000038
19. Tremblay M.-È., Stevens B., Sierra A., Wake H., Bessis A., Nimmerjahn A., The role of microglia in the healthy brain. Journal of Neuroscience 2011 31 45 16064 16069 2-s2.0-80755168115 10.1523/JNEUROSCI.4158- 11.2011
20. Hellwig S., Heinrich A., Biber K., The brain's best friend: microglial neurotoxicity revisited. Frontiers in Cellular Neuroscience 2013 10.3389/fncel.2013.00071
21. Paolicelli R. C., Bolasco G., Pagani F., Maggi L., Scianni M., Panzanelli P., Giustetto M., Ferreira T. A., Guiducci E., Dumas L., Ragozzino D., Gross C. T., Synaptic pruning by microglia is necessary for normal brain development. Science 2011 333 6048 1456 1458 2-s2.0-80052633284 10.1126/science.1202529
22. Cunningham C. L., Martinez-Cerdeno V., Noctor S. C., Microglia regulate the number of neural precursor cells in the developing cerebral cortex. Journal of Neuroscience 2013 33 4216 4233 10.1523/JNEUROSCI.3441-12.2013
23. Hoshiko M., Arnoux I., Avignone E., Yamamoto N., Audinat E., Deficiency of the microglial receptor CX3CR1 impairs postnatal functional development of thalamocortical synapses in the barrel cortex. Journal of Neuroscience 2012 32 15106 15111
24. Pascual O., Achour S. B., Rostaing P., Triller A., Bessis A., Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission. Proceedings of the National Academy of Sciences of the United States of America 2012 109 4 E197 E205 2-s2.0-84856384517 10.1073/pnas. 1111098109
25. Li Y., Du X. F., Liu C. S., Wen Z. L., Du J. L., Reciprocal regulation between resting microglial dynamics and neuronal activity in vivo. Developmental Cell 2012 23 6 1189 1202 10.1016/j.devcel.2012.10.027
26. Sierra A., Encinas J. M., Deudero J. J. P., Chancey J. H., Enikolopov G., Overstreet-Wadiche L. S., Tsirka S. E., Maletic-Savatic M., Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 2010 7 4 483 495 2-s2.0-77957328867 10.1016/j.stem.2010.08.014
27. Bechade C., Cantaut-Belarif Y., Bessis A., Microglial control of neuronal activity. Frontiers in Cellular Neuroscience 2013 7, article 32
28. Schafer D. P., Lehrman E. K., Kautzman A. G., 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
29. Wake H., Moorhouse A. J., Jinno S., Kohsaka S., Nabekura J., Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. Journal of Neuroscience 2009 29 13 3974 3980 2-s2.0-65249157852 10.1523/JNEUROSCI.4363-08.2009
30. Tremblay M.-È., Lowery R. L., Majewska A. K., Microglial interactions with synapses are modulated by visual experience. PLoS Biology 2010 8 11 2-s2.0-78649976052 10.1371/journal.pbio.1000527 e1000527
31. Tremblay M.-È., Zettel M. L., Ison J. R., Allen P. D., Majewska A. K., Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices. Glia 2012 60 4 541 558 2-s2.0-84856756074 10.1002/glia.22287
32. Sogn C. J., Puchades M., Gundersen V., Rare contacts between synapses and microglial processes containing high levels of Iba1 and actin-a postembedding immunogold study in the healthy rat brain. European Journal of Neuroscience 2013 32 1 2030 2040 10.1111/ejn.12213
33. Neumann H., Kotter M. R., Franklin R. J. M., Debris clearance by microglia: an essential link between degeneration and regeneration. Brain 2009 132 2 288 295 2-s2.0-60149098421 10.1093/brain/awn109
34. Sierra A., Abiega O., Shahraz A., Neumann H., Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis. Frontiers in Cellular Neuroscience 2013 7, article 6
35. Lu S.-M., Tremblay M.-È., King I. L., Qi J., Reynolds H. M., Marker D. F., Varrone J. J. P., Majewska A. K., Dewhurst S., Gelbard H. A., HIV-1 Tat-induced microgliosis and synaptic damage via interactions between peripheral and central myeloid cells. PLoS ONE 2011 6 9 2-s2.0-80052425327 10.1371/journal.pone.0023915 e23915
36. Marker D. F., Tremblay M.-È., Puccini J. M., The new small-molecule mixed-lineage kinase 3 inhibitor URMC-099 is neuroprotective and anti-inflammatory in models of human immunodeficiency virus-associated neurocognitive disorders. Journal of Neuroscience 2013 33 24 9998 10010 10.1523/JNEUROSCI.0598-13.2013
37. Keck T., Mrsic-Flogel T. D., Vaz Afonso M., Eysel U. T., Bonhoeffer T., Hübener M., Massive restructuring of neuronal circuits during functional reorganization of adult visual cortex. Nature Neuroscience 2008 11 10 1162 1167 2-s2.0-52949133401 10.1038/nn.2181
38. Majewska A., Sur M., Motility of dendritic spines in visual cortex in vivo: changes during the critical period and effects of visual deprivation. Proceedings of the National Academy of Sciences of the United States of America 2003 100 26 16024 16029 2-s2.0-0346734111 10.1073/pnas.2636949100 (Pubitemid 38021108)
39. Tropea D., Majewska A. K., Garcia R., Sur M., Structural dynamics of synapses in vivo correlate with functional changes during experience-dependent plasticity in visual cortex. Journal of Neuroscience 2010 30 33 11086 11095 2-s2.0-77955873697 10.1523/JNEUROSCI.1661-10.2010
40. Damani M. R., Zhao L., Fontainhas A. M., Amaral J., Fariss R. N., Wong W. T., Age-related alterations in the dynamic behavior of microglia. Aging Cell 2011 10 2 263 276 2-s2.0-79952610280 10.1111/j.1474-9726.2010.00660.x
41. Sierra A., Gottfried-Blackmore A. C., Mcewen B. S., Bulloch K., Microglia derived from aging mice exhibit an altered inflammatory profile. Glia 2007 55 4 412 424 2-s2.0-33846980461 10.1002/glia.20468
42. Luo X.-G., Ding J.-Q., Chen S.-D., Microglia in the aging brain: relevance to neurodegeneration. Molecular Neurodegeneration 2010 5 1, article 12 2-s2.0-77950826971 10.1186/1750-1326-5-12
43. Kettenmann H., Kirchhoff F., Verkhratsky A., Microglia: new roles for the synaptic stripper. Neuron 2013 77 10 18
44. Wong W. T., Microglial aging in the healthy CNS: phenotypes, drivers, and rejuvenation. Frontiers in Cellular Neuroscience 2013 7, article 22
45. Selkoe D. J., Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases. Nature Cell Biology 2004 6 11 1054 1061 2-s2.0-7944233158 10.1038/ncb1104-1054 (Pubitemid 39468006)
46. Haass C., Selkoe D. J., Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β -peptide. Nature Reviews Molecular Cell Biology 2007 8 2 101 112 2-s2.0-33847662852 10.1038/nrm2101 (Pubitemid 46432529)
47. Walsh D. M., Klyubin I., Fadeeva J. V., Cullen W. K., Anwyl R., Wolfe M. S., Rowan M. J., Selkoe D. J., Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature 2002 416 6880 535 539 2-s2.0-0037041426 10.1038/416535a (Pubitemid 34288854)
48. Townsend M., Shankar G. M., Mehta T., Walsh D. M., Selkoe D. J., Effects of secreted oligomers of amyloid β -protein on hippocampal synaptic plasticity: a potent role for trimers. Journal of Physiology 2006 572 2 477 492 2-s2.0-33645505550 10.1113/jphysiol.2005.103754
49. Terry R. D., Masliah E., Salmon D. P., Butters N., DeTeresa R., Hill R., Hansen L. A., Katzman R., Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Annals of Neurology 1991 30 4 572 580 2-s2.0-0025987048 10.1002/ana.410300410
50. Scheff S. W., Price D. A., Schmitt F. A., Mufson E. J., Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiology of Aging 2006 27 10 1372 1384 2-s2.0-33747760358 10.1016/j.neurobiolaging.2005.09.012 (Pubitemid 44279897)
51. Malinow R., New developments on the role of NMDA receptors in Alzheimer's disease. Current Opinion in Neurobiology 2012 22 3 559 563 10.1016/j.conb.2011. 09.001
52. McGeer E. G., McGeer P. L., Brain inflammation in Alzheimer disease and the therapeutic implications. Current Pharmaceutical Design 1999 5 10 821 836 2-s2.0-0032731763 (Pubitemid 29510788)
53. Meyer-Luehmann M., Spires-Jones T. L., Prada C., Garcia-Alloza M., de Calignon A., Rozkalne A., Koenigsknecht-Talboo J., Holtzman D. M., Bacskai B. J., Hyman B. T., Rapid appearance and local toxicity of amyloid- β plaques in a mouse model of Alzheimer's disease. Nature 2008 451 7179 720 724 2-s2.0-38949123792 10.1038/nature06616 (Pubitemid 351220570)
54. Simard A. R., Rivest S., Bone marrow stem cells have the ability to populate the entire central nervous system into fully differentiated parenchymal microglia. FASEB Journal 2004 18 9 998 1000 2-s2.0-6944234040 10.1096/fj.04-1517fje (Pubitemid 39561504)
55. Qiu W. Q., Ye Z., Kholodenko D., Seubert P., Selkoe D. J., Degradation of amyloid β -protein by a metalloprotease secreted by microglia and other neural and non-neural cells. Journal of Biological Chemistry 1997 272 10 6641 6646 2-s2.0-1842367306 10.1074/jbc.272.10.6641 (Pubitemid 27118149)
56. Paresce D. M., Ghosh R. N., Maxfield F. R., Microglial cells internalize aggregates of the Alzheimer's disease amyloid β -protein via a scavenger receptor. Neuron 1996 17 3 553 565 2-s2.0-0030248270 10.1016/S0896-6273(00) 80187-7 (Pubitemid 26322226)
57. El Khoury J., Hickman S. E., Thomas C. A., Cao L., Silverstein S. C., Loike J. D., Scavenger receptor-mediated adhesion of microglia to β -amyloid fibrils. Nature 1996 382 6593 716 719 2-s2.0-0029787599 10.1038/382716a0 (Pubitemid 26282177)
58. Koenigsknecht J., Landreth G., Microglial phagocytosis of fibrillar β -amyloid through a β 1 integrin-dependent mechanism. Journal of Neuroscience 2004 24 44 9838 9846 2-s2.0-7744235869 10.1523/JNEUROSCI.2557-04. 2004 (Pubitemid 39463564)
59. El Khoury J., Toft M., Hickman S. E., Means T. K., Terada K., Geula C., Luster A. D., Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nature Medicine 2007 13 4 432 438 2-s2.0-34147115541 10.1038/nm1555 (Pubitemid 46559828)
60. Nicoll J. A., Barton E., Boche D., Abeta species removal after A β 42 immunization. Journal of Neuropathology and Experimental Neurology 2006 65 11 1040 1048 10.1097/01.jnen.0000240466.10758.ce (Pubitemid 44684661)
61. Cramer P. E., Cirrito J. R., Wesson D. W., Lee C. Y. D., Karlo J. C., Zinn A. E., Casali B. T., Restivo J. L., Goebel W. D., James M. J., Brunden K. R., Wilson D. A., Landreth G. E., ApoE-directed therapeutics rapidly clear β -amyloid and reverse deficits in AD mouse models. Science 2012 335 6075 1503 1506 2-s2.0-84858794819 10.1126/science.1217697
62. Heneka M. T., Kummer M. P., Stutz A., NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 2013 493 674 678 10.1038/nature11729
63. Naert G., Rivest S., CC chemokine receptor 2 deficiency aggravates cognitive impairments and amyloid pathology in a transgenic mouse model of Alzheimer's disease. Journal of Neuroscience 2011 31 16 6208 6220 2-s2.0-79955775349 10.1523/JNEUROSCI.0299-11.2011
64. Grathwohl S. A., Kälin R. E., Bolmont T., Prokop S., Winkelmann G., Kaeser S. A., Odenthal J., Radde R., Eldh T., Gandy S., Aguzzi A., Staufenbiel M., Mathews P. M., Wolburg H., Heppner F. L., Jucker M., Formation and maintenance of Alzheimer's disease β -amyloid plaques in the absence of microglia. Nature Neuroscience 2009 12 11 1361 1363 2-s2.0-74949127437 10.1038/nn.2432
65. Hellwig S., Heinrich A., Biber K., The brain's best friend: microglial neurotoxicity revisited. Frontiers in Cellular Neuroscience 2013 7 1 11
66. Varvel N. H., Grathwohl S. A., Baumann F., Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells. Proceedings of the National Academy of Sciences of the United States of America 2012 109 44 18150 18155
67. Yan S. D., Chen X., Fu J., Chen M., Zhu H., Roher A., Slattery T., Zhao L., Nagashima M., Morser J., Migheli A., Nawroth P., Stern D., Schmidt A. M., RAGE and amyloid- β peptide neurotoxicity in Alzheimer's disease. Nature 1996 382 6593 685 691 2-s2.0-0013615899 10.1038/382685a0 (Pubitemid 26282167)
68. Weldon D. T., Rogers S. D., Ghilardi J. R., Finke M. P., Cleary J. P., O'Hare E., Esler W. P., Maggio J. E., Mantyh P. W., Fibrillar β -amyloid induces microglial phagocytosis, expression of inducible nitric oxide synthase, and loss of a select population of neurons in the rat CNS in vivo. Journal of Neuroscience 1998 18 6 2161 2173 2-s2.0-0032521111 (Pubitemid 28141421)
69. Harrison J. K., Jiang Y., Chen S., Xia Y., Maciejewski D., Mcnamara R. K., Streit W. J., Salafranca M. N., Adhikari S., Thompson D. A., Botti P., Bacon K. B., Feng L., Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proceedings of the National Academy of Sciences of the United States of America 1998 95 18 10896 10901 2-s2.0-13144279282 10.1073/pnas.95.18.10896 (Pubitemid 28413165)
70. Fuhrmann M., Bittner T., Jung C. K. E., Burgold S., Page R. M., Mitteregger G., Haass C., Laferla F. M., Kretzschmar H., Herms J., Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease. Nature Neuroscience 2010 13 4 411 413 2-s2.0-77950188666 10.1038/nn.2511
71. Yoshiyama Y., Higuchi M., Zhang B., Huang S.-M., Iwata N., Saido T., Maeda J., Suhara T., Trojanowski J. Q., Lee V. M.-Y., Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 2007 53 3 337 351 2-s2.0-33846538660 10.1016/j.neuron.2007.01.010 (Pubitemid 46161268)
72. Fraser D. A., Pisalyaput K., Tenner A. J., C1q enhances microglial clearance of apoptotic neurons and neuronal blebs, and modulates subsequent inflammatory cytokine production. Journal of Neurochemistry 2010 112 3 733 743 2-s2.0-73949103664 10.1111/j.1471-4159.2009.06494.x
73. Prusiner S. B., DeArmond S. J., Prion diseases and neurodegeneration. Annual Review of Neuroscience 1994 17 311 339 2-s2.0-0028213351 (Pubitemid 24117033)
74. Johnston A. R., Black C., Fraser J., MacLeod N., Scrapie infection alters the membrane and synaptic properties of mouse hippocampal CA1 pyramidal neurones. Journal of Physiology 1997 500 part 1 1 15 2-s2.0-0030956658 (Pubitemid 27165827)
75. Belichenko P. V., Brown D., Jeffrey M., Fraser J. R., Dendritic and synaptic alterations of hippocampal pyramidal neurones in scrapie-infected mice. Neuropathology and Applied Neurobiology 2000 26 2 143 149 2-s2.0-0000158060 10.1046/j.1365-2990.2000.026002143.x (Pubitemid 30251387)
76. Hogan R. N., Baringer J. R., Prusiner S. B., Scrapie infection diminishes spines and increases varicosities of dendrites in hamsters: a quantitative Golgi analysis. Journal of Neuropathology and Experimental Neurology 1987 46 4 461 473 2-s2.0-0023240262 (Pubitemid 17105153)
77. Landis D. M. D., Williams R. S., Masters C. L., Golgi and electron microscopic studies of spongiform encephalopathy. Neurology 1981 31 5 538 549 2-s2.0-0019394488 (Pubitemid 11126264)
78. Caughey B., Baron G. S., Prions and their partners in crime. Nature 2006 443 7113 803 810 2-s2.0-33750310849 10.1038/nature05294 (Pubitemid 44622685)
79. Jeffrey M., Halliday W. G., Bell J., Johnston A. R., Macleod N. K., Ingham C., Sayers A. R., Brown D. A., Fraser J. R., Synapse loss associated with abnormal PrP precedes neuronal degeneration in the scrapie-infected murine hippocampus. Neuropathology and Applied Neurobiology 2000 26 1 41 54 2-s2.0-0034016049 10.1046/j.1365-2990.2000.00216.x (Pubitemid 30145305)
80. Cunningham C., Deacon R., Wells H., Boche D., Waters S., Picanco Diniz C., Scott H., Rawlins J. N. P., Perry V. H., Synaptic changes characterize early behavioural signs in the ME7 model of murine prion disease. European Journal of Neuroscience 2003 17 10 2147 2155 2-s2.0-0038809966 10.1046/j.1460-9568.2003. 02662.x (Pubitemid 36713975)
81. Gray B. C., Siskova Z., Perry V. H., O'Connor V., Selective presynaptic degeneration in the synaptopathy associated with ME7-induced hippocampal pathology. Neurobiology of Disease 2009 35 1 63 74 2-s2.0-67349280983 10.1016/j.nbd.2009.04.001
82. Kitamoto T., Shin R.-W., Doh-ura K., Tomokane N., Miyazono M., Muramoto T., Tateishi J., Abnormal isoform of prion proteins accumulates in the synaptic structures of the central nervous system in patients with Creutzfeldt-Jakob disease. American Journal of Pathology 1992 140 6 1285 1294 2-s2.0-0026751775
83. Williams K., Ulvestad E., Antel J., Immune regulatory and effector properties of human adult microglia studied in vitro and in situ. Advances in Neuroimmunology 1994 4 3 273 281 2-s2.0-0028062835 (Pubitemid 24325874)
84. Manuelidis L., Fritch W., Xi Y.-G., Evolution of a strain of CJD that induces BSE-like plaques. Science 1997 277 5322 94 98 2-s2.0-0030758270 10.1126/science.277.5322.94 (Pubitemid 27450654)
85. Baker T. A., Protein unfolding: trapped in the act. Nature 1999 401 6748 29 30 2-s2.0-0033517317 10.1038/43341 (Pubitemid 29418423)
86. Boche D., Cunningham C., Docagne F., Scott H., Perry V. H., TGF β 1 regulates the inflammatory response during chronic neurodegeneration. Neurobiology of Disease 2006 22 3 638 650 2-s2.0-33744832035 10.1016/j.nbd.2006.01.004 (Pubitemid 43832134)
87. Fadok V. A., Chimini G., The phagocytosis of apoptotic cells. Seminars in Immunology 2001 13 6 365 372 2-s2.0-0035209395 10.1006/smim.2001.0333 (Pubitemid 33121962)
88. Guenther K., Deacon R. M. J., Perry V. H., Rawlins J. N. P., Early behavioural changes in scrapie-affected mice and the influence of dapsone. European Journal of Neuroscience 2001 14 2 401 409 2-s2.0-0034883360 10.1046/j.0953-816X.2001.01645.x (Pubitemid 32777645)
89. Šišková Z., Page A., O'Connor V., Perry V. H., Degenerating synaptic boutons in prion disease: microglia activation without synaptic stripping. American Journal of Pathology 2009 175 4 1610 1621 2-s2.0-73549119497 10.2353/ajpath.2009.090372
90. Siskova Z., Reynolds R. A., O'Connor V., Perry V. H., Brain region specific pre-synaptic and post-synaptic degeneration are early components of neuropathology in prion disease. PLoS ONE 2013 8 1 e55004 10.1371/journal.pone. 0055004
91. Sisková Z., Sanyal N. K., Orban A., O'Connor V., Perry V. H., Reactive hypertrophy of synaptic varicosities within the hippocampus of prion-infected mice. Biochemical Society Transactions 2010 38 2 471 475 2-s2.0-77953249289 10.1042/BST0380471
92. Bertoni-Freddari C., Fattoretti P., Casoli T., Meier-Ruge W., Ulrich J., Morphological adaptive response of the synaptic junctional zones in the human dentate gyrus during aging and Alzheimer's disease. Brain Research 1990 517 1-2 69 75 2-s2.0-0025283380 10.1016/0006-8993(90)91009-6 (Pubitemid 20207221)
93. DeKosky S. T., Scheff S. W., Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Annals of Neurology 1990 27 5 457 464 2-s2.0-0025269152 (Pubitemid 20149963)
94. Ronnevi L. O., Spontaneous phagocytosis of C-type synaptic terminals by spinal α -motoneurons in newborn kittens. An electron microscopic study. Brain Research 1979 162 2 189 199 2-s2.0-0018429316 10.1016/0006-8993(79)90283-X (Pubitemid 9167923)
95. Fuhrmann M., Mitteregger G., Kretzschmar H., Herms J., Dendritic pathology in prion disease starts at the synaptic spine. Journal of Neuroscience 2007 27 23 6224 6233 2-s2.0-34250007899 10.1523/JNEUROSCI.5062-06.2007 (Pubitemid 46890034)
96. Perry V. H., Teeling J., Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration. Seminars in Immunopathology 2013 35 5 601 612 10.1007/s00281-013-0382-8