Intrinsic DNA damage repair deficiency results in progressive microglia loss and replacement

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Intrinsic DNA damage repair deficiency results in progressive microglia loss and replacement. / Zhang, Xiaoming; Heng, Yang; Kooistra, Susanne M.; van Weering, Hilmar R.J.; Brummer, Maaike L.; Gerrits, Emma; Wesseling, Evelyn M.; Brouwer, Nieske; Nijboer, Tjalling W.; Dubbelaar, Marissa L.; Boddeke, Erik W.G.M.; Eggen, Bart J.L.

I: Glia, Bind 69, Nr. 3, 2021, s. 729-745.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Zhang, X, Heng, Y, Kooistra, SM, van Weering, HRJ, Brummer, ML, Gerrits, E, Wesseling, EM, Brouwer, N, Nijboer, TW, Dubbelaar, ML, Boddeke, EWGM & Eggen, BJL 2021, 'Intrinsic DNA damage repair deficiency results in progressive microglia loss and replacement', Glia, bind 69, nr. 3, s. 729-745. https://doi.org/10.1002/glia.23925

APA

Zhang, X., Heng, Y., Kooistra, S. M., van Weering, H. R. J., Brummer, M. L., Gerrits, E., Wesseling, E. M., Brouwer, N., Nijboer, T. W., Dubbelaar, M. L., Boddeke, E. W. G. M., & Eggen, B. J. L. (2021). Intrinsic DNA damage repair deficiency results in progressive microglia loss and replacement. Glia, 69(3), 729-745. https://doi.org/10.1002/glia.23925

Vancouver

Zhang X, Heng Y, Kooistra SM, van Weering HRJ, Brummer ML, Gerrits E o.a. Intrinsic DNA damage repair deficiency results in progressive microglia loss and replacement. Glia. 2021;69(3):729-745. https://doi.org/10.1002/glia.23925

Author

Zhang, Xiaoming ; Heng, Yang ; Kooistra, Susanne M. ; van Weering, Hilmar R.J. ; Brummer, Maaike L. ; Gerrits, Emma ; Wesseling, Evelyn M. ; Brouwer, Nieske ; Nijboer, Tjalling W. ; Dubbelaar, Marissa L. ; Boddeke, Erik W.G.M. ; Eggen, Bart J.L. / Intrinsic DNA damage repair deficiency results in progressive microglia loss and replacement. I: Glia. 2021 ; Bind 69, Nr. 3. s. 729-745.

Bibtex

@article{e7fdcfb4f95a44758d6e1cd92ee5e97e,
title = "Intrinsic DNA damage repair deficiency results in progressive microglia loss and replacement",
abstract = "The DNA excision repair protein Ercc1 is important for nucleotide excision, double strand DNA break, and interstrand DNA crosslink repair. In constitutive Ercc1-knockout mice, microglia display increased phagocytosis, proliferation and an enhanced responsiveness to lipopolysaccharide (LPS)-induced peripheral inflammation. However, the intrinsic effects of Ercc1-deficiency on microglia are unclear. In this study, Ercc1 was specifically deleted from Cx3cr1-expressing cells and changes in microglia morphology and immune responses at different times after deletion were determined. Microglia numbers were reduced with approximately 50% at 2–12 months after Ercc1 deletion. Larger and more ramified microglia were observed following Ercc1 deletion both in vivo and in organotypic hippocampal slice cultures. Ercc1-deficient microglia were progressively lost, and during this period, microglia proliferation was transiently increased. Ercc1-deficient microglia were gradually replaced by nondeficient microglia carrying a functional Ercc1 allele. In contrast to constitutive Ercc1-deficient mice, microglia-specific deletion of Ercc1 did not induce microglia activation or increase their responsiveness to a systemic LPS challenge. Gene expression analysis suggested that Ercc1 deletion in microglia induced a transient aging signature, which was different from a priming or disease-associated microglia gene expression profile.",
keywords = "aging, DNA damage repair, Ercc1, microglia, morphometrics",
author = "Xiaoming Zhang and Yang Heng and Kooistra, {Susanne M.} and {van Weering}, {Hilmar R.J.} and Brummer, {Maaike L.} and Emma Gerrits and Wesseling, {Evelyn M.} and Nieske Brouwer and Nijboer, {Tjalling W.} and Dubbelaar, {Marissa L.} and Boddeke, {Erik W.G.M.} and Eggen, {Bart J.L.}",
year = "2021",
doi = "10.1002/glia.23925",
language = "English",
volume = "69",
pages = "729--745",
journal = "GLIA",
issn = "0894-1491",
publisher = "JohnWiley & Sons, Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Intrinsic DNA damage repair deficiency results in progressive microglia loss and replacement

AU - Zhang, Xiaoming

AU - Heng, Yang

AU - Kooistra, Susanne M.

AU - van Weering, Hilmar R.J.

AU - Brummer, Maaike L.

AU - Gerrits, Emma

AU - Wesseling, Evelyn M.

AU - Brouwer, Nieske

AU - Nijboer, Tjalling W.

AU - Dubbelaar, Marissa L.

AU - Boddeke, Erik W.G.M.

AU - Eggen, Bart J.L.

PY - 2021

Y1 - 2021

N2 - The DNA excision repair protein Ercc1 is important for nucleotide excision, double strand DNA break, and interstrand DNA crosslink repair. In constitutive Ercc1-knockout mice, microglia display increased phagocytosis, proliferation and an enhanced responsiveness to lipopolysaccharide (LPS)-induced peripheral inflammation. However, the intrinsic effects of Ercc1-deficiency on microglia are unclear. In this study, Ercc1 was specifically deleted from Cx3cr1-expressing cells and changes in microglia morphology and immune responses at different times after deletion were determined. Microglia numbers were reduced with approximately 50% at 2–12 months after Ercc1 deletion. Larger and more ramified microglia were observed following Ercc1 deletion both in vivo and in organotypic hippocampal slice cultures. Ercc1-deficient microglia were progressively lost, and during this period, microglia proliferation was transiently increased. Ercc1-deficient microglia were gradually replaced by nondeficient microglia carrying a functional Ercc1 allele. In contrast to constitutive Ercc1-deficient mice, microglia-specific deletion of Ercc1 did not induce microglia activation or increase their responsiveness to a systemic LPS challenge. Gene expression analysis suggested that Ercc1 deletion in microglia induced a transient aging signature, which was different from a priming or disease-associated microglia gene expression profile.

AB - The DNA excision repair protein Ercc1 is important for nucleotide excision, double strand DNA break, and interstrand DNA crosslink repair. In constitutive Ercc1-knockout mice, microglia display increased phagocytosis, proliferation and an enhanced responsiveness to lipopolysaccharide (LPS)-induced peripheral inflammation. However, the intrinsic effects of Ercc1-deficiency on microglia are unclear. In this study, Ercc1 was specifically deleted from Cx3cr1-expressing cells and changes in microglia morphology and immune responses at different times after deletion were determined. Microglia numbers were reduced with approximately 50% at 2–12 months after Ercc1 deletion. Larger and more ramified microglia were observed following Ercc1 deletion both in vivo and in organotypic hippocampal slice cultures. Ercc1-deficient microglia were progressively lost, and during this period, microglia proliferation was transiently increased. Ercc1-deficient microglia were gradually replaced by nondeficient microglia carrying a functional Ercc1 allele. In contrast to constitutive Ercc1-deficient mice, microglia-specific deletion of Ercc1 did not induce microglia activation or increase their responsiveness to a systemic LPS challenge. Gene expression analysis suggested that Ercc1 deletion in microglia induced a transient aging signature, which was different from a priming or disease-associated microglia gene expression profile.

KW - aging

KW - DNA damage repair

KW - Ercc1

KW - microglia

KW - morphometrics

U2 - 10.1002/glia.23925

DO - 10.1002/glia.23925

M3 - Journal article

C2 - 33068332

AN - SCOPUS:85092619503

VL - 69

SP - 729

EP - 745

JO - GLIA

JF - GLIA

SN - 0894-1491

IS - 3

ER -

ID: 250815923