Top

Published in:

Open Access 01-12-2023 | Positron Emission Tomography | Research

Depletion and activation of microglia impact metabolic connectivity of the mouse brain

Authors: Johannes Gnörich, Anika Reifschneider, Karin Wind, Artem Zatcepin, Sebastian T. Kunte, Philipp Beumers, Laura M. Bartos, Thomas Wiedemann, Maximilian Grosch, Xianyuan Xiang, Maryam K. Fard, Francois Ruch, Georg Werner, Mara Koehler, Luna Slemann, Selina Hummel, Nils Briel, Tanja Blume, Yuan Shi, Gloria Biechele, Leonie Beyer, Florian Eckenweber, Maximilian Scheifele, Peter Bartenstein, Nathalie L. Albert, Jochen Herms, Sabina Tahirovic, Christian Haass, Anja Capell, Sibylle Ziegler, Matthias Brendel

Published in: Journal of Neuroinflammation | Issue 1/2023

Abstract

Aim

We aimed to investigate the impact of microglial activity and microglial FDG uptake on metabolic connectivity, since microglial activation states determine FDG–PET alterations. Metabolic connectivity refers to a concept of interacting metabolic brain regions and receives growing interest in approaching complex cerebral metabolic networks in neurodegenerative diseases. However, underlying sources of metabolic connectivity remain to be elucidated.

Materials and methods

We analyzed metabolic networks measured by interregional correlation coefficients (ICCs) of FDG–PET scans in WT mice and in mice with mutations in progranulin (Grn) or triggering receptor expressed on myeloid cells 2 (Trem2) knockouts (^−/−) as well as in double mutant Grn^−/−/Trem2^−/− mice. We selected those rodent models as they represent opposite microglial signatures with disease associated microglia in Grn^−/− mice and microglia locked in a homeostatic state in Trem2^−/− mice; however, both resulting in lower glucose uptake of the brain. The direct influence of microglia on metabolic networks was further determined by microglia depletion using a CSF1R inhibitor in WT mice at two different ages. Within maps of global mean scaled regional FDG uptake, 24 pre-established volumes of interest were applied and assigned to either cortical or subcortical networks. ICCs of all region pairs were calculated and z-transformed prior to group comparisons. FDG uptake of neurons, microglia, and astrocytes was determined in Grn^−/− and WT mice via assessment of single cell tracer uptake (scRadiotracing).

Results

Microglia depletion by CSF1R inhibition resulted in a strong decrease of metabolic connectivity defined by decrease of mean cortical ICCs in WT mice at both ages studied (6–7 m; p = 0.0148, 9–10 m; p = 0.0191), when compared to vehicle-treated age-matched WT mice. Grn^−/−, Trem2^−/− and Grn^−/−/Trem2^−/− mice all displayed reduced FDG–PET signals when compared to WT mice. However, when analyzing metabolic networks, a distinct increase of ICCs was observed in Grn^−/− mice when compared to WT mice in cortical (p < 0.0001) and hippocampal (p < 0.0001) networks. In contrast, Trem2^−/− mice did not show significant alterations in metabolic connectivity when compared to WT. Furthermore, the increased metabolic connectivity in Grn^−/− mice was completely suppressed in Grn^−/−/Trem2^−/− mice. Grn^−/− mice exhibited a severe loss of neuronal FDG uptake (− 61%, p < 0.0001) which shifted allocation of cellular brain FDG uptake to microglia (42% in Grn^−/− vs. 22% in WT).

Conclusions

Presence, absence, and activation of microglia have a strong impact on metabolic connectivity of the mouse brain. Enhanced metabolic connectivity is associated with increased microglial FDG allocation.

Available only for authorised users

Ahmed Z, Sheng H, Xu YF, Lin WL, Innes AE, Gass J, etn al. Accelerated lipofuscinosis and ubiquitination in granulin knockout mice suggest a role for progranulin in successful aging. Am J Pathol. 2010;177(1):311–24. https://doi.org/10.2353/ajpath.2010.090915.CrossRefPubMedPubMedCentral

Aiello M, Cavaliere C, Salvatore M. Hybrid PET/MR imaging and brain connectivity. Front Neurosci. 2016;10:64. https://doi.org/10.3389/fnins.2016.00064.CrossRefPubMedPubMedCentral

Backes H, Walberer M, Ladwig A, Rueger MA, Neumaier B, Endepols H, et al. Glucose consumption of inflammatory cells masks metabolic deficits in the brain. Neuroimage. 2016;128:54–62. https://doi.org/10.1016/j.neuroimage.2015.12.044.CrossRefPubMed

Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C, et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature. 2006;442(7105):916–9. https://doi.org/10.1038/nature05016.CrossRefPubMed

Bartos LM, Kunte ST, Beumers P, Xiang X, Wind K, Ziegler S, et al. Single cell radiotracer allocation via immunomagentic sorting (scRadiotracing) to disentangle PET signals at cellular resolution. J Nucl Med. 2022. https://doi.org/10.2967/jnumed.122.264171.CrossRefPubMed

Biechele G, Franzmeier N, Blume T, Ewers M, Luque JM, Eckenweber F, et al. Glial activation is moderated by sex in response to amyloidosis but not to tau pathology in mouse models of neurodegenerative diseases. J Neuroinflamm. 2020;17(1):374. https://doi.org/10.1186/s12974-020-02046-2.CrossRef

Bohnen NI, Djang DS, Herholz K, Anzai Y, Minoshima S. Effectiveness and safety of 18F-FDG PET in the evaluation of dementia: a review of the recent literature. J Nucl Med. 2012;53(1):59–71. https://doi.org/10.2967/jnumed.111.096578.CrossRefPubMed

Brendel M, Focke C, Blume T, Peters F, Deussing M, Probst F, et al. Time courses of cortical glucose metabolism and microglial activity across the life span of wild-type mice: a PET study. J Nucl Med. 2017;58(12):1984–90. https://doi.org/10.2967/jnumed.117.195107.CrossRefPubMed

DiNuzzo M, Mangia S, Maraviglia B, Giove F. Glycogenolysis in astrocytes supports blood-borne glucose channeling not glycogen-derived lactate shuttling to neurons: evidence from mathematical modeling. J Cereb Blood Flow Metab. 2010;30(12):1895–904. https://doi.org/10.1038/jcbfm.2010.151.CrossRefPubMedPubMedCentral

10.

Eckenweber F, Medina-Luque J, Blume T, Sacher C, Biechele G, Wind K, et al. Longitudinal TSPO expression in tau transgenic P301S mice predicts increased tau accumulation and deteriorated spatial learning. J Neuroinflamm. 2020;17(1):208. https://doi.org/10.1186/s12974-020-01883-5.CrossRef

11.

Elmore MR, Najafi AR, Koike MA, Dagher NN, Spangenberg EE, Rice RA, et al. Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain. Neuron. 2014;82(2):380–97. https://doi.org/10.1016/j.neuron.2014.02.040.CrossRefPubMedPubMedCentral

12.

Filiano AJ, Martens LH, Young AH, Warmus BA, Zhou P, Diaz-Ramirez G, et al. Dissociation of frontotemporal dementia-related deficits and neuroinflammation in progranulin haploinsufficient mice. J Neurosci. 2013;33(12):5352–61. https://doi.org/10.1523/JNEUROSCI.6103-11.2013.CrossRefPubMedPubMedCentral

13.

Fornito A, Bullmore ET. Connectomics: a new paradigm for understanding brain disease. Eur Neuropsychopharmacol. 2015;25(5):733–48. https://doi.org/10.1016/j.euroneuro.2014.02.011.CrossRefPubMed

14.

Fornito A, Zalesky A, Breakspear M. The connectomics of brain disorders. Nat Rev Neurosci. 2015;16(3):159–72. https://doi.org/10.1038/nrn3901.CrossRefPubMed

15.

Friston KJ. Functional and effective connectivity: a review. Brain Connect. 2011;1(1):13–36. https://doi.org/10.1089/brain.2011.0008.CrossRefPubMed

16.

Funfschilling U, Supplie LM, Mahad D, Boretius S, Saab AS, Edgar J, et al. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature. 2012;485(7399):517–21. https://doi.org/10.1038/nature11007.CrossRefPubMedPubMedCentral

17.

Gavillet M, Allaman I, Magistretti PJ. Modulation of astrocytic metabolic phenotype by proinflammatory cytokines. Glia. 2008;56(9):975–89. https://doi.org/10.1002/glia.20671.CrossRefPubMed

18.

Gotzl JK, Brendel M, Werner G, Parhizkar S, Sebastian Monasor L, Kleinberger G, et al. Opposite microglial activation stages upon loss of PGRN or TREM2 result in reduced cerebral glucose metabolism. EMBO Mol Med. 2019;11(6):e9711. https://doi.org/10.15252/emmm.201809711.CrossRefPubMedPubMedCentral

19.

Grosch M, Beyer L, Lindner M, Kaiser L, Ahmadi SA, Stockbauer A, et al. Metabolic connectivity-based single subject classification by multi-regional linear approximation in the rat. Neuroimage. 2021;235:118007. https://doi.org/10.1016/j.neuroimage.2021.118007.CrossRefPubMed

20.

Grosch M, Lindner M, Bartenstein P, Brandt T, Dieterich M, Ziegler S, Zwergal A. Dynamic whole-brain metabolic connectivity during vestibular compensation in the rat. Neuroimage. 2021;226:117588. https://doi.org/10.1016/j.neuroimage.2020.117588.CrossRefPubMed

21.

Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Alzheimer Genetic Analysis, G. TREM2 variants in Alzheimer’s disease. N Engl J Med. 2013;368(2):117–27. https://doi.org/10.1056/NEJMoa1211851.CrossRefPubMed

22.

Guneykaya D, Ivanov A, Hernandez DP, Haage V, Wojtas B, Meyer N, et al. Transcriptional and translational differences of microglia from male and female brains. Cell Rep. 2018;24(10):2773-2783e2776. https://doi.org/10.1016/j.celrep.2018.08.001.CrossRefPubMed

23.

Haass C, Hung AY, Selkoe DJ. Processing of beta-amyloid precursor protein in microglia and astrocytes favors an internal localization over constitutive secretion. J Neurosci. 1991;11(12):3783–93.CrossRefPubMedPubMedCentral

24.

Han J, Fan Y, Zhou K, Blomgren K, Harris RA. Uncovering sex differences of rodent microglia. J Neuroinflamm. 2021;18(1):74. https://doi.org/10.1186/s12974-021-02124-z.CrossRef

25.

Hanamsagar R, Alter MD, Block CS, Sullivan H, Bolton JL, Bilbo SD. Generation of a microglial developmental index in mice and in humans reveals a sex difference in maturation and immune reactivity. Glia. 2017;65(9):1504–20. https://doi.org/10.1002/glia.23176.CrossRefPubMedPubMedCentral

26.

Henry RJ, Ritzel RM, Barrett JP, Doran SJ, Jiao Y, Leach JB, et al. Microglial depletion with CSF1R inhibitor during chronic phase of experimental traumatic brain injury reduces neurodegeneration and neurological deficits. J Neurosci. 2020;40(14):2960–74. https://doi.org/10.1523/JNEUROSCI.2402-19.2020.CrossRefPubMedPubMedCentral

27.

Herholz K, Carter SF, Jones M. Positron emission tomography imaging in dementia. Br J Radiol. 2007;80(Spec No 2):S160-167. https://doi.org/10.1259/bjr/97295129.CrossRefPubMed

28.

Huber M, Beyer L, Prix C, Schonecker S, Palleis C, Rauchmann BS, et al. Metabolic correlates of dopaminergic loss in dementia with Lewy bodies. Mov Disord. 2020;35(4):595–605. https://doi.org/10.1002/mds.27945.CrossRefPubMed

29.

Ishii K, Sakamoto S, Sasaki M, Kitagaki H, Yamaji S, Hashimoto M, et al. Cerebral glucose metabolism in patients with frontotemporal dementia. J Nucl Med. 1998;39(11):1875–8.PubMed

30.

Jalilianhasanpour R, Beheshtian E, Sherbaf G, Sahraian S, Sair HI. Functional connectivity in neurodegenerative disorders: Alzheimer’s disease and frontotemporal dementia. Top Magn Reson Imaging. 2019;28(6):317–24. https://doi.org/10.1097/RMR.0000000000000223.CrossRefPubMed

31.

Keren-Shaul H, Spinrad A, Weiner A, Matcovitch-Natan O, Dvir-Szternfeld R, Ulland TK, et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell. 2017;169(7):1276-1290e1217. https://doi.org/10.1016/j.cell.2017.05.018.CrossRefPubMed

32.

Kleinberger G, Brendel M, Mracsko E, Wefers B, Groeneweg L, Xiang X, et al. The FTD-like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism. EMBO J. 2017;36(13):1837–53. https://doi.org/10.15252/embj.201796516.CrossRefPubMedPubMedCentral

33.

Kuntner C, Kesner AL, Bauer M, Kremslehner R, Wanek T, Mandler M, et al. Limitations of small animal PET imaging with [18F]FDDNP and FDG for quantitative studies in a transgenic mouse model of Alzheimer’s disease. Mol Imaging Biol. 2009;11(4):236–40. https://doi.org/10.1007/s11307-009-0198-z.CrossRefPubMed

34.

Lee Y, Morrison BM, Li Y, Lengacher S, Farah MH, Hoffman PN, et al. Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature. 2012;487(7408):443–8. https://doi.org/10.1038/nature11314.CrossRefPubMedPubMedCentral

35.

Liu CC, Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 2013;9(2):106–18. https://doi.org/10.1038/nrneurol.2012.263.CrossRefPubMedPubMedCentral

36.

Ma Y, Hof PR, Grant SC, Blackband SJ, Bennett R, Slatest L, et al. A three-dimensional digital atlas database of the adult C57BL/6J mouse brain by magnetic resonance microscopy. Neuroscience. 2005;135(4):1203–15. https://doi.org/10.1016/j.neuroscience.2005.07.014.CrossRefPubMed

37.

Malpetti M, Carli G, Sala A, Cerami C, Marcone A, Iannaccone S, et al. Variant-specific vulnerability in metabolic connectivity and resting-state networks in behavioural variant of frontotemporal dementia. Cortex. 2019;120:483–97. https://doi.org/10.1016/j.cortex.2019.07.018.CrossRefPubMed

38.

Martens LH, Zhang J, Barmada SJ, Zhou P, Kamiya S, Sun B, et al. Progranulin deficiency promotes neuroinflammation and neuron loss following toxin-induced injury. J Clin Invest. 2012;122(11):3955–9. https://doi.org/10.1172/JCI63113.CrossRefPubMedPubMedCentral

39.

Mason S. Lactate shuttles in neuroenergetics-homeostasis, Allostasis and Beyond. Front Neurosci. 2017;11:43. https://doi.org/10.3389/fnins.2017.00043.CrossRefPubMedPubMedCentral

40.

Mazaheri F, Snaidero N, Kleinberger G, Madore C, Daria A, Werner G, et al. TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury. EMBO Rep. 2017;18(7):1186–98. https://doi.org/10.15252/embr.201743922.CrossRefPubMedPubMedCentral

41.

Minoshima S, Frey KA, Koeppe RA, Foster NL, Kuhl DE. A diagnostic approach in Alzheimer’s disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med. 1995;36(7):1238–48.PubMed

42.

Morbelli S, Chincarini A, Brendel M, Rominger A, Bruffaerts R, Vandenberghe R, et al. Metabolic patterns across core features in dementia with Lewy bodies. Ann Neurol. 2019;85(5):715–25. https://doi.org/10.1002/ana.25453.CrossRefPubMed

43.

Nelson LH, Warden S, Lenz KM. Sex differences in microglial phagocytosis in the neonatal hippocampus. Brain Behav Immun. 2017;64:11–22. https://doi.org/10.1016/j.bbi.2017.03.010.CrossRefPubMedPubMedCentral

44.

Niethammer M, Eidelberg D. Metabolic brain networks in translational neurology: concepts and applications. Ann Neurol. 2012;72(5):635–47. https://doi.org/10.1002/ana.23631.CrossRefPubMedPubMedCentral

45.

Oh SJ, Ahn H, Jung KH, Han SJ, Nam KR, Kang KJ, et al. Evaluation of the neuroprotective effect of microglial depletion by CSF-1R inhibition in a Parkinson’s animal model. Mol Imaging Biol. 2020;22(4):1031–42. https://doi.org/10.1007/s11307-020-01485-w.CrossRefPubMed

46.

Overhoff F, Brendel M, Jaworska A, Korzhova V, Delker A, Probst F, et al. Automated spatial brain normalization and hindbrain white matter reference tissue give improved [(18)F]-Florbetaben PET quantitation in Alzheimer’s model mice. Front Neurosci. 2016;10:45. https://doi.org/10.3389/fnins.2016.00045.CrossRefPubMedPubMedCentral

47.

Palleis C, Sauerbeck J, Beyer L, Harris S, Schmitt J, Morenas-Rodriguez E, et al. In vivo assessment of neuroinflammation in 4-repeat tauopathies. Mov Disord. 2020. https://doi.org/10.1002/mds.28395.CrossRefPubMed

48.

Passamonti L, Tsvetanov KA, Jones PS, Bevan-Jones WR, Arnold R, Borchert RJ, et al. Neuroinflammation and functional connectivity in Alzheimer’s disease: interactive influences on cognitive performance. J Neurosci. 2019;39(36):7218–26. https://doi.org/10.1523/JNEUROSCI.2574-18.2019.CrossRefPubMedPubMedCentral

49.

Pellerin L, Magistretti PJ. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci USA. 1994;91(22):10625–9. https://doi.org/10.1073/pnas.91.22.10625.CrossRefPubMedPubMedCentral

50.

Petkau TL, Hill A, Leavitt BR. Core neuropathological abnormalities in progranulin-deficient mice are penetrant on multiple genetic backgrounds. Neuroscience. 2016;315:175–95. https://doi.org/10.1016/j.neuroscience.2015.12.006.CrossRefPubMed

51.

Petkau TL, Neal SJ, Milnerwood A, Mew A, Hill AM, Orban P, et al. Synaptic dysfunction in progranulin-deficient mice. Neurobiol Dis. 2012;45(2):711–22. https://doi.org/10.1016/j.nbd.2011.10.016.CrossRefPubMed

52.

Poisnel G, Herard AS, El Tannir El Tayara N, Bourrin E, Volk A, Kober F, Dhenain M. Increased regional cerebral glucose uptake in an APP/PS1 model of Alzheimer’s disease. Neurobiol Aging. 2012;33(9):1995–2005. https://doi.org/10.1016/j.neurobiolaging.2011.09.026.CrossRefPubMed

53.

Reifschneider A, Robinson S, van Lengerich B, Gnorich J, Logan T, Heindl S, et al. Loss of TREM2 rescues hyperactivation of microglia, but not lysosomal deficits and neurotoxicity in models of progranulin deficiency. EMBO J. 2022;41:e109108. https://doi.org/10.15252/embj.2021109108.CrossRefPubMedPubMedCentral

54.

Sala A, Perani D. Brain molecular connectivity in neurodegenerative diseases: recent advances and new perspectives using positron emission tomography. Front Neurosci. 2019;13:617. https://doi.org/10.3389/fnins.2019.00617.CrossRefPubMedPubMedCentral

55.

Sanabria-Diaz G, Martinez-Montes E, Melie-Garcia L, Alzheimer’s Disease Neuroimaging I. Glucose metabolism during resting state reveals abnormal brain networks organization in the Alzheimer’s disease and mild cognitive impairment. PLoS ONE. 2013;8(7):e68860. https://doi.org/10.1371/journal.pone.0068860.CrossRefPubMedPubMedCentral

56.

Schwarz JM, Sholar PW, Bilbo SD. Sex differences in microglial colonization of the developing rat brain. J Neurochem. 2012;120(6):948–63. https://doi.org/10.1111/j.1471-4159.2011.07630.x.CrossRefPubMedPubMedCentral

57.

Shi Y, Cui M, Ochs K, Brendel M, Strubing FL, Briel N, et al. Long-term diazepam treatment enhances microglial spine engulfment and impairs cognitive performance via the mitochondrial 18 kDa translocator protein (TSPO). Nat Neurosci. 2022;25(3):317–29. https://doi.org/10.1038/s41593-022-01013-9.CrossRefPubMed

58.

Silverman DH, Small GW, Chang CY, Lu CS, Kung De Aburto MA, Chen W, et al. Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome. JAMA. 2001;286(17):2120–7. https://doi.org/10.1001/jama.286.17.2120.CrossRefPubMed

59.

Sporns O. Structure and function of complex brain networks. Dialogues Clin Neurosci. 2013;15(3):247–62.CrossRefPubMedPubMedCentral

60.

Titov D, Diehl-Schmid J, Shi K, Perneczky R, Zou N, Grimmer T, et al. Metabolic connectivity for differential diagnosis of dementing disorders. J Cereb Blood Flow Metab. 2017;37(1):252–62. https://doi.org/10.1177/0271678X15622465.CrossRefPubMed

61.

Toussaint PJ, Perlbarg V, Bellec P, Desarnaud S, Lacomblez L, Doyon J, et al. Resting state FDG-PET functional connectivity as an early biomarker of Alzheimer’s disease using conjoint univariate and independent component analyses. Neuroimage. 2012;63(2):936–46. https://doi.org/10.1016/j.neuroimage.2012.03.091.CrossRefPubMed

62.

Tripathi M, Tripathi M, Damle N, Kushwaha S, Jaimini A, D’Souza MM, et al. Differential diagnosis of neurodegenerative dementias using metabolic phenotypes on F-18 FDG PET/CT. Neuroradiol J. 2014;27(1):13–21. https://doi.org/10.15274/NRJ-2014-10002.CrossRefPubMedPubMedCentral

63.

Villa A, Gelosa P, Castiglioni L, Cimino M, Rizzi N, Pepe G, et al. Sex-specific features of microglia from adult mice. Cell Rep. 2018;23(12):3501–11. https://doi.org/10.1016/j.celrep.2018.05.048.CrossRefPubMedPubMedCentral

64.

Wang L, Pavlou S, Du X, Bhuckory M, Xu H, Chen M. Glucose transporter 1 critically controls microglial activation through facilitating glycolysis. Mol Neurodegener. 2019;14(1):2. https://doi.org/10.1186/s13024-019-0305-9.CrossRefPubMedPubMedCentral

65.

Wehrl HF, Hossain M, Lankes K, Liu CC, Bezrukov I, Martirosian P, et al. Simultaneous PET-MRI reveals brain function in activated and resting state on metabolic, hemodynamic and multiple temporal scales. Nat Med. 2013;19(9):1184–9. https://doi.org/10.1038/nm.3290.CrossRefPubMed

66.

Werner G, Damme M, Schludi M, Gnorich J, Wind K, Fellerer K, et al. Loss of TMEM106B potentiates lysosomal and FTLD-like pathology in progranulin-deficient mice. EMBO Rep. 2020;21(10):e50241. https://doi.org/10.15252/embr.202050241.CrossRefPubMedPubMedCentral

67.

Xiang X, Wind K, Wiedemann T, Blume T, Shi Y, Briel N, et al. Microglial activation states drive glucose uptake and FDG-PET alterations in neurodegenerative diseases. Sci Transl Med. 2021;13(615):eabe5640. https://doi.org/10.1126/scitranslmed.abe5640.CrossRefPubMed

68.

Yakushev I, Drzezga A, Habeck C. Metabolic connectivity: methods and applications. Curr Opin Neurol. 2017;30(6):677–85. https://doi.org/10.1097/WCO.0000000000000494.CrossRefPubMed

69.

Yin F, Banerjee R, Thomas B, Zhou P, Qian L, Jia T, et al. Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. J Exp Med. 2010;207(1):117–28. https://doi.org/10.1084/jem.20091568.CrossRefPubMedPubMedCentral

70.

Zimmer ER, Parent MJ, Souza DG, Leuzy A, Lecrux C, Kim HI, et al. [(18)F]FDG PET signal is driven by astroglial glutamate transport. Nat Neurosci. 2017;20(3):393–5. https://doi.org/10.1038/nn.4492.CrossRefPubMedPubMedCentral

Title: Depletion and activation of microglia impact metabolic connectivity of the mouse brain
Authors: Johannes Gnörich
Anika Reifschneider
Karin Wind
Artem Zatcepin
Sebastian T. Kunte
Philipp Beumers
Laura M. Bartos
Thomas Wiedemann
Maximilian Grosch
Xianyuan Xiang
Maryam K. Fard
Francois Ruch
Georg Werner
Mara Koehler
Luna Slemann
Selina Hummel
Nils Briel
Tanja Blume
Yuan Shi
Gloria Biechele
Leonie Beyer
Florian Eckenweber
Maximilian Scheifele
Peter Bartenstein
Nathalie L. Albert
Jochen Herms
Sabina Tahirovic
Christian Haass
Anja Capell
Sibylle Ziegler
Matthias Brendel
Publication date: 01-12-2023
Publisher: BioMed Central
Keyword: Positron Emission Tomography
Published in: Journal of Neuroinflammation / Issue 1/2023
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-023-02735-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Depletion and activation of microglia impact metabolic connectivity of the mouse brain

Abstract

Aim

Materials and methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Aim

Materials and methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2023

Novel CH25H+ and OASL+ microglia subclusters play distinct roles in cerebral ischemic stroke

Correction: Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer's disease

Dysbiosis of gut microbiota inhibits NMNAT2 to promote neurobehavioral deficits and oxidative stress response in the 6-OHDA-lesioned rat model of Parkinson’s disease

Ogt-mediated O-GlcNAcylation inhibits astrocytes activation through modulating NF-κB signaling pathway

Intracellular deposits of amyloid-beta influence the ability of human iPSC-derived astrocytes to support neuronal function

A brain cytokine-independent switch in cortical activity marks the onset of sickness behavior triggered by acute peripheral inflammation