Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Clayton, EL, Mancuso, R, Nielsen, TT, Mizielinska, S, Holmes, H, Powell, N, Norona, F, Overgaard Larsen, J, Milioto, C, Wilson, KM, Lythgoe, MF, Ourselin, S, Nielsen, JE, Johannsen, P, Holm, I, Collinge, J, Frej, A, Oliver, PL, Gomez-Nicola, D & Isaacs, AM 2017, 'Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation' Human Molecular Genetics, pp. 873-887. https://doi.org/10.1093/hmg/ddx003

APA

CBE

Clayton EL, Mancuso R, Nielsen TT, Mizielinska S, Holmes H, Powell N, Norona F, Overgaard Larsen J, Milioto C, Wilson KM, Lythgoe MF, Ourselin S, Nielsen JE, Johannsen P, Holm I, Collinge J, Frej A, Oliver PL, Gomez-Nicola D, Isaacs AM. 2017. Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation. Human Molecular Genetics. 873-887. https://doi.org/10.1093/hmg/ddx003

MLA

Vancouver

Author

Clayton, Emma L ; Mancuso, Renzo ; Nielsen, Troels Tolstrup ; Mizielinska, Sarah ; Holmes, Holly ; Powell, Nicholas ; Norona, Frances ; Overgaard Larsen, Jytte ; Milioto, Carmelo ; Wilson, Katherine M ; Lythgoe, Mark F ; Ourselin, Sebastian ; Nielsen, Jörgen E ; Johannsen, Peter ; Holm, Ida ; Collinge, John ; Frej, A ; Oliver, Peter L ; Gomez-Nicola, Diego ; Isaacs, Adrian M. / Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation. In: Human Molecular Genetics. 2017 ; pp. 873-887.

Bibtex

@article{b4306871e46f4995b17d660273fd2095,
title = "Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation",
abstract = "Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD-like changes in social behaviour. These data are the first to show neurodegeneration in mice expressing mutant CHMP2B and indicate that our mouse model is able to recapitulate neurodegenerative changes observed in FTD. Neuroinflammation has been increasingly implicated in neurodegeneration, including FTD. Therefore, we investigated neuroinflammation in our CHMP2B mutant mice. We observed very early microglial proliferation that develops into a clear pro-inflammatory phenotype at late stages. Importantly, we also observed a similar inflammatory profile in CHMP2B patient frontal cortex. Aberrant microglial function has also been implicated in FTD caused by GRN, MAPT and C9orf72 mutations. The presence of early microglial changes in our CHMP2B mutant mice indicates neuroinflammation may be a contributing factor to the neurodegeneration observed in FTD.",
author = "Clayton, {Emma L} and Renzo Mancuso and Nielsen, {Troels Tolstrup} and Sarah Mizielinska and Holly Holmes and Nicholas Powell and Frances Norona and {Overgaard Larsen}, Jytte and Carmelo Milioto and Wilson, {Katherine M} and Lythgoe, {Mark F} and Sebastian Ourselin and Nielsen, {J{\"o}rgen E} and Peter Johannsen and Ida Holm and John Collinge and A Frej and Oliver, {Peter L} and Diego Gomez-Nicola and Isaacs, {Adrian M}",
note = "{\circledC} The Author 2017. Published by Oxford University Press.",
year = "2017",
month = "3",
day = "1",
doi = "10.1093/hmg/ddx003",
language = "English",
pages = "873--887",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",

}

RIS

TY - JOUR

T1 - Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation

AU - Clayton, Emma L

AU - Mancuso, Renzo

AU - Nielsen, Troels Tolstrup

AU - Mizielinska, Sarah

AU - Holmes, Holly

AU - Powell, Nicholas

AU - Norona, Frances

AU - Overgaard Larsen, Jytte

AU - Milioto, Carmelo

AU - Wilson, Katherine M

AU - Lythgoe, Mark F

AU - Ourselin, Sebastian

AU - Nielsen, Jörgen E

AU - Johannsen, Peter

AU - Holm, Ida

AU - Collinge, John

AU - Frej, A

AU - Oliver, Peter L

AU - Gomez-Nicola, Diego

AU - Isaacs, Adrian M

N1 - © The Author 2017. Published by Oxford University Press.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD-like changes in social behaviour. These data are the first to show neurodegeneration in mice expressing mutant CHMP2B and indicate that our mouse model is able to recapitulate neurodegenerative changes observed in FTD. Neuroinflammation has been increasingly implicated in neurodegeneration, including FTD. Therefore, we investigated neuroinflammation in our CHMP2B mutant mice. We observed very early microglial proliferation that develops into a clear pro-inflammatory phenotype at late stages. Importantly, we also observed a similar inflammatory profile in CHMP2B patient frontal cortex. Aberrant microglial function has also been implicated in FTD caused by GRN, MAPT and C9orf72 mutations. The presence of early microglial changes in our CHMP2B mutant mice indicates neuroinflammation may be a contributing factor to the neurodegeneration observed in FTD.

AB - Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD-like changes in social behaviour. These data are the first to show neurodegeneration in mice expressing mutant CHMP2B and indicate that our mouse model is able to recapitulate neurodegenerative changes observed in FTD. Neuroinflammation has been increasingly implicated in neurodegeneration, including FTD. Therefore, we investigated neuroinflammation in our CHMP2B mutant mice. We observed very early microglial proliferation that develops into a clear pro-inflammatory phenotype at late stages. Importantly, we also observed a similar inflammatory profile in CHMP2B patient frontal cortex. Aberrant microglial function has also been implicated in FTD caused by GRN, MAPT and C9orf72 mutations. The presence of early microglial changes in our CHMP2B mutant mice indicates neuroinflammation may be a contributing factor to the neurodegeneration observed in FTD.

U2 - 10.1093/hmg/ddx003

DO - 10.1093/hmg/ddx003

M3 - Journal article

SP - 873

EP - 887

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

ER -

ID: 49732970