Identification of a chronic non-neurodegenerative microglia activation state in a mouse model of peroxisomal β-oxidation deficiency

GLIA

Volumn 63, Issue 9, 2015, Pages 1606-1620

  Verheijden, Simon ^a   Beckers, Lien ^a   Casazza, Andrea ^a,b   Butovsky, Oleg ^c   Mazzone, Massimiliano ^a,b   Baes, Myriam ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^c HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Microglia; mTOR; Multifunctional protein 2; Neuroinflammation; Peroxisomes; Phagocytosis

Indexed keywords

LIPOPOLYSACCHARIDE; MAMMALIAN TARGET OF RAPAMYCIN; HSD17B4 PROTEIN, MOUSE; MTOR PROTEIN, MOUSE; PEROXISOMAL MULTIFUNCTIONAL PROTEIN 2; TARGET OF RAPAMYCIN KINASE;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL ACTIVATION; CONTROLLED STUDY; DOWN REGULATION; FLOW CYTOMETRY; GENE EXPRESSION PROFILING; IMMUNOHISTOCHEMISTRY; MICROGLIA; MOUSE; MOUSE MODEL; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PEROXISOME; PHAGOCYTOSIS; PRIORITY JOURNAL; ALTERNATIVE RNA SPLICING; ANIMAL; BRAIN; CELL CULTURE; DEFICIENCY; DISEASE MODEL; GENETICS; HOMEOSTASIS; IMMUNOMODULATION; KNOCKOUT MOUSE; METABOLISM; NERVE CELL; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; SPINAL CORD; TRANSGENIC MOUSE;

ALTERNATIVE SPLICING; AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; BRAIN; CELLS, CULTURED; DISEASE MODELS, ANIMAL; HOMEOSTASIS; LIPOPOLYSACCHARIDES; MICE, KNOCKOUT; MICE, TRANSGENIC; MICROGLIA; NEUROIMMUNOMODULATION; NEURONS; PEROXISOMAL MULTIFUNCTIONAL PROTEIN-2; PHAGOCYTOSIS; SPINAL CORD; TOR SERINE-THREONINE KINASES;

EID: 84949086663     PISSN: 08941491     EISSN: 10981136     Source Type: Journal    
DOI: 10.1002/glia.22831     Document Type: Article

References (59)

1. Baes M, Huyghe S, Carmeliet P, Declercq PE, Collen D, Mannaerts GP, Van Veldhoven PP. 2000. Inactivation of the peroxisomal multifunctional protein-2 in mice impedes the degradation of not only 2-methyl branched fatty acids and bile acid intermediates but also of very long chain fatty acids. J Biol Chem 275:16329-16336.
2. Biber K, Owens T, Boddeke E. 2014. What is microglia neurotoxicity (not)? Glia 62:841-854.
3. Block ML, Zecca L, Hong JS. 2007. Microglia-mediated neurotoxicity: Uncovering the molecular mechanisms. Nat Rev Neurosci 8:57-69.
4. Bottelbergs A, Verheijden S, Hulshagen L, Gutmann DH, Goebbels S, Nave KA, Kassmann C, Baes M. 2010. Axonal integrity in the absence of functional peroxisomes from projection neurons and astrocytes. Glia 58:1532-1543.
5. Brown GC, Neher JJ. 2014. Microglial phagocytosis of live neurons. Nat Rev Neurosci 15:209-216.
6. Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ, Gabriely G, Koeglsperger T, Dake B, Wu PM, Doykan CE, Fanek Z, Liu L, Chen Z, Rothstein JD, Ransohoff RM, Gygi SP, Antel JP, Weiner HL. 2014. Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat Neurosci 17:131-143.
7. Butovsky O, Siddiqui S, Gabriely G, Lanser AJ, Dake B, Murugaiyan G, Doykan CE, Wu PM, Gali RR, Iyer LK, Lawson R, Berry J, Krichevsky AM, Cudkowicz ME, Weiner HL. 2012. Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS. J Clin Invest 122:3063-3087.
8. Byles V, Covarrubias AJ, Ben-Sahra I, Lamming DW, Sabatini DM, Manning BD, Horng T. 2013. The TSC-mTOR pathway regulates macrophage polarization. Nat Commun 4:2834.
9. Cartier N, Aubourg P. 2010. Hematopoietic stem cell transplantation and hematopoietic stem cell gene therapy in X-linked adrenoleukodystrophy. Brain Pathol 20:857-862.
10. Cartier N, Hacein-Bey-Abina S, Bartholomae CC, Veres G, Schmidt M, Kutschera I, Vidaud M, Abel U, Dal-Cortivo L, Caccavelli L, Mahlaoui N, Kiermer V, Mittelstaedt D, Bellesme C, Lahlou N, Lefrere F, Blanche S, Audit M, Payen E, Leboulch P, l'Homme B, Bougneres P, Von KC, Fischer A, Cavazzana-Calvo M, Aubourg P. 2009. Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science 326:818-823.
11. Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, Giamarellos-Bourboulis EJ, Martens JH, Rao NA, Aghajanirefah A, Manjeri GR, Li Y, Ifrim DC, Arts RJ, van der Veer BM, Deen PM, Logie C, O'Neill LA, Willems P, van de Veerdonk FL, van der Meer JW, Ng A, Joosten LA, Wijmenga C, Stunnenberg HG, Xavier RJ, Netea MG. 2014. mTOR- and HIF-1alpha-mediated aerobic glycolysis as metabolic basis for trained immunity. Science 345:1250684.
12. Cherry JD, Olschowka JA, O'Banion MK. 2014. Neuroinflammation and m2 microglia: the good, the bad, and the inflamed. J Neuroinflammation 11:98.
13. Chiu IM, Morimoto ET, Goodarzi H, Liao JT, O'Keeffe S, Phatnani HP, Muratet M, Carroll MC, Levy S, Tavazoie S, Myers RM, Maniatis T. 2013. A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model. Cell Rep 4:385-401.
14. De Haas AH, Boddeke HW, Brouwer N, Biber K. 2007. Optimized isolation enables ex vivo analysis of microglia from various central nervous system regions. Glia 55:1374-1384.
15. Derecki NC, Cronk JC, Kipnis J. 2013. The role of microglia in brain maintenance: Implications for Rett syndrome. Trends Immunol 34:144-150.
16. Duvel K, Yecies JL, Menon S, Raman P, Lipovsky AI, Souza AL, Triantafellow E, Ma Q, Gorski R, Cleaver S, Vander Heiden MG, MacKeigan JP, Finan PM, Clish CB, Murphy LO, Manning BD. 2010. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell 39:171-183.
17. Estevez AG, Sahawneh MA, Lange PS, Bae N, Egea M, Ratan RR. 2006. Arginase 1 regulation of nitric oxide production is key to survival of trophic factor-deprived motor neurons. J Neurosci 26:8512-8516.
18. Ferdinandusse S, Denis S, Mooyer PA, Dekker C, Duran M, Soorani-Lunsing RJ, Boltshauser E, Macaya A, Gartner J, Majoie CB, Barth PG, Wanders RJ, Poll-The BT. 2006a. Clinical and biochemical spectrum of D-bifunctional protein deficiency. Ann Neurol 59:92-104.
19. Ferdinandusse S, Denis S, Mooyer PAW, Dekker C, Duran M, Soorani-Lunsing RJ, Boltshauser E, Macaya A, Gartner J, Majoie CBLM, Barth PG, Wanders RJA, Poll-The BT. 2006b. Clinical and biochemical spectrum of D-bifunctional protein deficiency. Ann Neurol 59:92-104.
20. Gautier EL, Shay T, Miller J, Greter M, Jakubzick C, Ivanov S, Helft J, Chow A, Elpek KG, Gordonov S, Mazloom AR, Ma'ayan A, Chua WJ, Hansen TH, Turley SJ, Merad M, Randolph GJ. 2012. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat Immunol 13:1118-1128.
21. Giulietti A, Overbergh L, Valckx D, Decallonne B, Bouillon R, Mathieu C. 2001. An overview of real-time quantitative PCR: Applications to quantify cytokine gene expression. Methods 25:386-401.
22. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. 2010. Mechanisms underlying inflammation in neurodegeneration. Cell 140:918-934.
23. Gomez-Nicola D, Fransen NL, Suzzi S, Perry VH. 2013. Regulation of microglial proliferation during chronic neurodegeneration. J Neurosci 33:2481-2493.
24. Hay N, Sonenberg N. 2004. Upstream and downstream of mTOR. Genes Dev 18:1926-1945.
25. Hickman SE, Kingery ND, Ohsumi TK, Borowsky ML, Wang LC, Means TK, El Khoury J. 2013. The microglial sensome revealed by direct RNA sequencing. Nat Neurosci 16:1896-1905.
26. Hochberg Y, Benjamini Y. 1990. More powerful procedures for multiple significance testing. Stat Med 9:811-818.
27. Hughes V. 2012. Microglia: The constant gardeners. Nature 485:570-572.
28. Hulshagen L, Krysko O, Bottelbergs A, Huyghe S, Klein R, Van Veldhoven PP, De Deyn PP, D'Hooge R, Hartmann D, Baes M. 2008. Absence of functional peroxisomes from mouse CNS causes dysmyelination and axon degeneration. J Neurosci 28:4015-4027.
29. Huyghe S, Mannaerts GP, Baes M, Van Veldhoven PP. 2006a. Peroxisomal multifunctional protein-2: The enzyme, the patients and the knockout mouse model. BBA Mol Cell Biol L 1761:973-994.
30. Huyghe S, Schmalbruch H, De Gendt K, Verhoeven G, Guillou F, Van Veldhoven PP, Baes M, 2006b. Peroxisomal multifunctional protein 2 is essential for lipid homeostasis in sertoli cells and for male fertility in mice. Endocrinology 147:2228-2236.
31. Huyghe S, Schmalbruch H, Hulshagen L, Van Veldhoven PP, Baes M, Hartmann D. 2006c. Peroxisomal multifunctional protein-2 deficiency causes motor deficits and glial lesions in the adult CNS. Am J Pathol 168:1321-1334.
32. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP. 2003. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4:249-264.
33. Jia Y, Qi C, Zhang Z, Hashimoto T, Rao MS, Huyghe S, Suzuki Y, Van Veldhoven PP, Baes M, Reddy JK. 2003. Overexpression of peroxisome proliferator-activated receptor-alpha (PPARalpha)-regulated genes in liver in the absence of peroxisome proliferation in mice deficient in both L- and D- forms of enoyl-CoA hydratase/dehydrogenase enzymes of peroxisomal beta-oxidation system. J Biol Chem 278:47232-47239.
34. Kemp S, Berger J, Aubourg P. 2012. X-linked adrenoleukodystrophy: Metabolic, genetic and clinical aspects. BBA-Mol Basis Dis 1822:1465-1474.
35. Khan A, Wei XC, Snyder FF, Mah JK, Waterham H, Wanders RJ. 2010. Neurodegeneration in D-bifunctional protein deficiency: diagnostic clues and natural history using serial magnetic resonance imaging. Neuroradiol 52:1163-1166.
36. Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. 2009. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci 29:13435-13444.
37. Lange PS, Langley B, Lu P, Ratan RR. 2004. Novel roles for arginase in cell survival, regeneration, and translation in the central nervous system. J Nutr 134:2812S-2817S.
38. Liao B, Zhao W, Beers DR, Henkel JS, Appel SH. 2012. Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS. Exp Neurol 237:147-152.
39. Lu DY, Liou HC, Tang CH, Fu WM. 2006. Hypoxia-induced iNOS expression in microglia is regulated by the PI3-kinase/akt/mTOR signaling pathway and activation of hypoxia inducible factor-1alpha. Biochem Pharmacol 72:992-1000.
40. Lu Q, Gao L, Huang L, Ruan L, Yang J, Huang W, Li Z, Zhang Y, Jin K, Zhuge Q. 2014. Inhibition of mammalian target of rapamycin improves neurobehavioral deficit and modulates immune response after intracerebral hemorrhage in rat. J Neuroinflammation 11:44.
41. Luo L, Wall AA, Yeo JC, Condon ND, Norwood SJ, Schoenwaelder S, Chen KW, Jackson S, Jenkins BJ, Hartland EL, Schroder K, Collins BM, Sweet MJ, Stow JL. 2014. Rab8a interacts directly with PI3Kgamma to modulate TLR4-driven PI3K and mTOR signalling. Nat Commun 5:4407.
42. Norden DM, Godbout JP. 2013. Review: Microglia of the aged brain: Primed to be activated and resistant to regulation. Neuropathol Appl Neurobiol 39:19-34.
43. Olah M, Raj D, Brouwer N, De Haas AH, Eggen BJ, Den Dunnen WF, Biber KP, Boddeke HW. 2012. An optimized protocol for the acute isolation of human microglia from autopsy brain samples. Glia 60:96-111.
44. Parkhurst CN, Yang G, Ninan I, Savas JN, Yates JR III, Lafaille JJ, Hempstead BL, Littman DR, Gan WB. 2013. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155:1596-1609.
45. Perry VH, Holmes C. 2014. Microglial priming in neurodegenerative disease. Nat Rev Neurol 10:217-224.
46. Prinz M, Mildner A, 2011. Microglia in the CNS: Immigrants from another world. Glia 59:177-187.
47. Prinz M, Priller J, 2014. Microglia and brain macrophages in the molecular age: From origin to neuropsychiatric disease. Nat Rev Neurosci 15:300-312.
48. Ransohoff RM, Perry VH. 2009. Microglial physiology: Unique stimuli, specialized responses. Annu Rev Immunol 27:119-145.
49. Saeed S, Quintin J, Kerstens HH, Rao NA, Aghajanirefah A, Matarese F, Cheng SC, Ratter J, Berentsen K, van der Ent MA, Sharifi N, Janssen-Megens EM, Ter Huurne M, Mandoli A, van Schaik T, Ng A, Burden F, Downes K, Frontini M, Kumar V, Giamarellos-Bourboulis EJ, Ouwehand WH, van der Meer JW, Joosten LA, Wijmenga C, Martens JH, Xavier RJ, Logie C, Netea MG, Stunnenberg HG. 2014. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science 345:1251086.
50. Salter MW, Beggs S, 2014. Sublime microglia: Expanding roles for the guardians of the CNS. Cell 158:15-24.
51. Sanagi T, Yuasa S, Nakamura Y, Suzuki E, Aoki M, Warita H, Itoyama Y, Uchino S, Kohsaka S, Ohsawa K. 2010. Appearance of phagocytic microglia adjacent to motoneurons in spinal cord tissue from a presymptomatic transgenic rat model of amyotrophic lateral sclerosis. J Neurosci Res 88:2736-2746.
52. Satoh J, Tabunoki H, Ishida T, Yagishita S, Jinnai K, Futamura N, Kobayashi M, Toyoshima I, Yoshioka T, Enomoto K, Arai N, Arima K. 2011. Immunohistochemical characterization of microglia in Nasu-hakola disease brains. Neuropathology 31:363-375.
53. Sekiguchi A, Kanno H, Ozawa H, Yamaya S, Itoi E. 2012. Rapamycin promotes autophagy and reduces neural tissue damage and locomotor impairment after spinal cord injury in mice. J Neurotrauma 29:946-956.
54. Tremblay ME, Lowery RL, Majewska AK. 2010. Microglial interactions with synapses are modulated by visual experience. PLoS Biol 8:e1000527.
55. Van der Knaap MS, Wassmer E, Wolf NI, Ferreira P, Topcu M, Wanders RJ, Waterham HR, Ferdinandusse S. 2012. MRI as diagnostic tool in early-onset peroxisomal disorders. Neurology 78:1304-1308.
56. Van Vliet EA, Forte G, Holtman L, den Burger JC, Sinjewel A, de Vries HE, Aronica E, Gorter JA. 2012. Inhibition of mammalian target of rapamycin reduces epileptogenesis and blood-brain barrier leakage but not microglia activation. Epilepsia 53:1254-1263.
57. Verheijden S, Bottelbergs A, Krysko O, Krysko DV, Beckers L, De Munter S, Van Veldhoven PP, Wyns S, Kulik W, Nave KA, Ramer MS, Carmeliet P, Kassmann CM, Baes M. 2013. Peroxisomal multifunctional protein-2 deficiency causes neuroinflammation and degeneration of purkinje cells independent of very long chain fatty acid accumulation. Neurobiol Dis 58:258-269.
58. Yamasaki R, Lu H, Butovsky O, Ohno N, Rietsch AM, Cialic R, Wu PM, Doykan CE, Lin J, Cotleur AC, Kidd G, Zorlu MM, Sun N, Hu W, Liu L, Lee JC, Taylor SE, Uehlein L, Dixon D, Gu J, Floruta CM, Zhu M, Charo IF, Weiner HL, Ransohoff RM. 2014. Differential roles of microglia and monocytes in the inflamed central nervous system. J Exp Med 211:1533-1549.
59. Zhan Y, Paolicelli RC, Sforazzini F, Weinhard L, Bolasco G, Pagani F, Vyssotski AL, Bifone A, Gozzi A, Ragozzino D, Gross CT. 2014. Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat Neurosci 17:400-406.