دورية أكاديمية
أعرض في EDS

Microglial CD68 and L-ferritin upregulation in response to phosphorylated-TDP-43 pathology in the amyotrophic lateral sclerosis brain.

التفاصيل البيبلوغرافية
العنوان: Microglial CD68 and L-ferritin upregulation in response to phosphorylated-TDP-43 pathology in the amyotrophic lateral sclerosis brain.
المؤلفون: Swanson MEV; School of Biological Sciences, University of Auckland, Auckland, New Zealand.; Centre for Brain Research, University of Auckland, Auckland, New Zealand., Mrkela M; School of Biological Sciences, University of Auckland, Auckland, New Zealand.; Centre for Brain Research, University of Auckland, Auckland, New Zealand., Murray HC; Centre for Brain Research, University of Auckland, Auckland, New Zealand.; Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand., Cao MC; Centre for Brain Research, University of Auckland, Auckland, New Zealand.; Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand., Turner C; Department of Anatomical Pathology, Pathology and Laboratory Medicine, Auckland City Hospital, Auckland, New Zealand., Curtis MA; Centre for Brain Research, University of Auckland, Auckland, New Zealand.; Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand., Faull RLM; Centre for Brain Research, University of Auckland, Auckland, New Zealand.; Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand., Walker AK; Queensland Brain Institute, University of Queensland, Brisbane, Australia., Scotter EL; School of Biological Sciences, University of Auckland, Auckland, New Zealand. emma.scotter@auckland.ac.nz.; Centre for Brain Research, University of Auckland, Auckland, New Zealand. emma.scotter@auckland.ac.nz.
المصدر: Acta neuropathologica communications [Acta Neuropathol Commun] 2023 Apr 28; Vol. 11 (1), pp. 69. Date of Electronic Publication: 2023 Apr 28.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101610673 Publication Model: Electronic Cited Medium: Internet ISSN: 2051-5960 (Electronic) Linking ISSN: 20515960 NLM ISO Abbreviation: Acta Neuropathol Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2013]-
مواضيع طبية MeSH: Amyotrophic Lateral Sclerosis*/pathology, Humans ; Mice ; Animals ; Microglia/metabolism ; Apoferritins/metabolism ; Up-Regulation ; Brain/pathology ; DNA-Binding Proteins/metabolism
مستخلص: Microglia, the innate immune cells of the brain, are activated by damage or disease. In mouse models of amyotrophic lateral sclerosis (ALS), microglia shift from neurotrophic to neurotoxic states with disease progression. It remains unclear how human microglia change relative to the TAR DNA-binding protein 43 (TDP-43) aggregation that occurs in 97% of ALS cases. Here we examine spatial relationships between microglial activation and TDP-43 pathology in brain tissue from people with ALS and from a TDP-43-driven ALS mouse model. Post-mortem human brain tissue from the Neurological Foundation Human Brain Bank was obtained from 10 control and 10 ALS cases in parallel with brain tissue from a bigenic NEFH-tTA/tetO-hTDP-43∆NLS (rNLS) mouse model of ALS at disease onset, early disease, and late disease stages. The spatiotemporal relationship between microglial activation and ALS pathology was determined by investigating microglial functional marker expression in brain regions with low and high TDP-43 burden at end-stage human disease: hippocampus and motor cortex, respectively. Sections were immunohistochemically labelled with a two-round multiplexed antibody panel against; microglial functional markers (L-ferritin, HLA-DR, CD74, CD68, and Iba1), a neuronal marker, an astrocyte marker, and pathological phosphorylated TDP-43 (pTDP-43). Single-cell levels of microglial functional markers were quantified using custom analysis pipelines and mapped to anatomical regions and ALS pathology. We identified a significant increase in microglial Iba1 and CD68 expression in the human ALS motor cortex, with microglial CD68 being significantly correlated with pTDP-43 pathology load. We also identified two subpopulations of microglia enriched in the ALS motor cortex that were defined by high L-ferritin expression. A similar pattern of microglial changes was observed in the rNLS mouse, with an increase first in CD68 and then in L-ferritin expression, with both occurring only after pTDP-43 inclusions were detectable. Our data strongly suggest that microglia are phagocytic at early-stage ALS but transition to a dysfunctional state at end-stage disease, and that these functional states are driven by pTDP-43 aggregation. Overall, these findings enhance our understanding of microglial phenotypes and function in ALS.
(© 2023. The Author(s).)
References: J Neuroimmune Pharmacol. 2009 Dec;4(4):371-9. (PMID: 19680817)
F1000Prime Rep. 2014 Mar 03;6:13. (PMID: 24669294)
Brain Behav Immun. 2011 Jul;25(5):1025-35. (PMID: 21176785)
Acta Neuropathol. 2009 Oct;118(4):475-85. (PMID: 19513731)
Cell. 2017 Jun 15;169(7):1276-1290.e17. (PMID: 28602351)
J Neurosci Res. 2010 Sep;88(12):2736-46. (PMID: 20648658)
Acta Neuropathol. 2015 Nov;130(5):643-60. (PMID: 26197969)
Ann Neurol. 2013 Jul;74(1):20-38. (PMID: 23686809)
Nat Neurosci. 2018 Mar;21(3):329-340. (PMID: 29463850)
Blood. 1993 Mar 15;81(6):1607-13. (PMID: 7680921)
Neurobiol Dis. 2020 Jul;141:104877. (PMID: 32360664)
Acta Neuropathol Commun. 2020 Oct 20;8(1):170. (PMID: 33081847)
J Neuroinflammation. 2010 Jan 28;7:8. (PMID: 20109233)
J Cell Sci. 2000 Sep;113 ( Pt 17):3073-84. (PMID: 10934045)
Exp Neurol. 2012 Sep;237(1):147-52. (PMID: 22735487)
Lancet Neurol. 2014 Nov;13(11):1108-1113. (PMID: 25300936)
Amyotroph Lateral Scler. 2006 Dec;7(4):211-20. (PMID: 17127559)
Brain. 2023 Jul 14;:. (PMID: 37450566)
Nat Neurosci. 2023 Jan;26(1):150-162. (PMID: 36482247)
Nat Commun. 2019 Nov 28;10(1):5415. (PMID: 31780669)
Prog Neurobiol. 1999 Apr;57(6):563-81. (PMID: 10221782)
Neurol Neuroimmunol Neuroinflamm. 2020 Jul 15;7(5):. (PMID: 32669313)
Nat Protoc. 2006;1(6):2719-32. (PMID: 17406528)
J Neuroinflammation. 2017 Jun 26;14(1):129. (PMID: 28651542)
Sci Rep. 2020 Jul 16;10(1):11693. (PMID: 32678124)
Neurotherapeutics. 2015 Apr;12(2):352-63. (PMID: 25652699)
Eur J Neurosci. 2021 Sep;54(6):6237-6255. (PMID: 34390052)
Neurobiol Dis. 2019 Oct;130:104523. (PMID: 31276795)
Eur J Neurosci. 2016 May;43(10):1340-51. (PMID: 26946061)
Neurogenetics. 2018 Aug;19(3):189-204. (PMID: 29982879)
Physiol Rev. 2011 Apr;91(2):461-553. (PMID: 21527731)
J Neuroinflammation. 2022 Feb 28;19(1):58. (PMID: 35227277)
Neuron. 2022 Nov 2;110(21):3458-3483. (PMID: 36327895)
PLoS One. 2012;7(4):e35241. (PMID: 22529995)
Acta Neuropathol. 2013 Feb;125(2):273-88. (PMID: 22961620)
Nat Rev Neurol. 2010 Apr;6(4):193-201. (PMID: 20234358)
Mol Biol Cell. 2005 Nov;16(11):5061-9. (PMID: 16107560)
Alzheimers Res Ther. 2015 Aug 19;7(1):56. (PMID: 26286145)
Acta Neuropathol. 2012 Mar;123(3):395-407. (PMID: 22210083)
J Pathol. 2022 Dec;258(4):366-381. (PMID: 36070099)
Commun Biol. 2022 Jan 24;5(1):88. (PMID: 35075270)
Acta Neuropathol Commun. 2020 Jul 2;8(1):98. (PMID: 32616036)
Acta Neuropathol Commun. 2020 Jul 14;8(1):109. (PMID: 32665027)
PLoS One. 2012;7(4):e36000. (PMID: 22558300)
Neuroscience. 2017 Aug 15;357:37-55. (PMID: 28576725)
PLoS One. 2012;7(6):e39216. (PMID: 22720079)
Nat Neurosci. 2022 Jan;25(1):26-38. (PMID: 34916658)
Cell Rep. 2013 Jul 25;4(2):385-401. (PMID: 23850290)
Nature. 2019 Feb;566(7745):496-502. (PMID: 30787437)
Brain Res Mol Brain Res. 1998 Jun 1;57(1):1-9. (PMID: 9630473)
Brain. 2013 Sep;136(Pt 9):2677-96. (PMID: 23943781)
Biochem Pharmacol. 2014 Apr 15;88(4):594-604. (PMID: 24445162)
Exp Neurol. 2015 Nov;273:24-35. (PMID: 26222336)
Acta Neuropathol. 2017 Aug;134(2):241-254. (PMID: 28409281)
Nat Commun. 2019 Nov 28;10(1):5416. (PMID: 31780648)
Acta Neuropathol Commun. 2014 Sep 26;2:142. (PMID: 25257319)
Biochem Biophys Res Commun. 1996 Jul 25;224(3):855-62. (PMID: 8713135)
Dev Neurosci. 2018;40(2):145-161. (PMID: 29680832)
Glia. 2008 Aug 1;56(10):1048-60. (PMID: 18442088)
Neurooncol Adv. 2021 May 04;3(1):vdab031. (PMID: 34286275)
Acta Neuropathol. 2018 Sep;136(3):445-459. (PMID: 29943193)
Science. 2006 Oct 6;314(5796):130-3. (PMID: 17023659)
Acta Neuropathol Commun. 2021 Aug 19;9(1):140. (PMID: 34412701)
Acta Neuropathol. 1988;76(6):550-7. (PMID: 2974227)
Glia. 2012 Oct;60(10):1506-17. (PMID: 22740309)
Neurobiol Dis. 2015 Feb;74:359-76. (PMID: 25500340)
EMBO Mol Med. 2020 Feb 7;12(2):e10919. (PMID: 31858749)
Mol Neurodegener. 2015 Aug 01;10:34. (PMID: 26227626)
فهرسة مساهمة: Keywords: Amyotrophic lateral sclerosis; CD68; L-ferritin; Microglia; TDP-43
المشرفين على المادة: 9013-31-4 (Apoferritins)
0 (DNA-Binding Proteins)
0 (TDP-43 protein, mouse)
تواريخ الأحداث: Date Created: 20230429 Date Completed: 20230501 Latest Revision: 20231101
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC10142752
DOI: 10.1186/s40478-023-01561-6
PMID: 37118836
قاعدة البيانات: MEDLINE
الوصف
تدمد:2051-5960
DOI:10.1186/s40478-023-01561-6