Publication

Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes

Gorter, R. P., Stephenson, J., Nutma, E., Anink, J., de Jonge, J. C., Baron, W., Jahreiss, M. -C., Belien, J. A. M., van Noort, J. M., Mijnsbergen, C., Aronica, E. & Amor, S., Aug-2019, In : Neuropathology and Applied Neurobiology. 45, 5, p. 459-475 17 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Gorter, R. P., Stephenson, J., Nutma, E., Anink, J., de Jonge, J. C., Baron, W., ... Amor, S. (2019). Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes. Neuropathology and Applied Neurobiology, 45(5), 459-475. https://doi.org/10.1111/nan.12525

Author

Gorter, R. P. ; Stephenson, J. ; Nutma, E. ; Anink, J. ; de Jonge, J. C. ; Baron, W. ; Jahreiss, M. -C. ; Belien, J. A. M. ; van Noort, J. M. ; Mijnsbergen, C. ; Aronica, E. ; Amor, S. / Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes. In: Neuropathology and Applied Neurobiology. 2019 ; Vol. 45, No. 5. pp. 459-475.

Harvard

Gorter, RP, Stephenson, J, Nutma, E, Anink, J, de Jonge, JC, Baron, W, Jahreiss, M-C, Belien, JAM, van Noort, JM, Mijnsbergen, C, Aronica, E & Amor, S 2019, 'Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes', Neuropathology and Applied Neurobiology, vol. 45, no. 5, pp. 459-475. https://doi.org/10.1111/nan.12525

Standard

Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes. / Gorter, R. P.; Stephenson, J.; Nutma, E.; Anink, J.; de Jonge, J. C.; Baron, W.; Jahreiss, M. -C.; Belien, J. A. M.; van Noort, J. M.; Mijnsbergen, C.; Aronica, E.; Amor, S.

In: Neuropathology and Applied Neurobiology, Vol. 45, No. 5, 08.2019, p. 459-475.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Gorter RP, Stephenson J, Nutma E, Anink J, de Jonge JC, Baron W et al. Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes. Neuropathology and Applied Neurobiology. 2019 Aug;45(5):459-475. https://doi.org/10.1111/nan.12525


BibTeX

@article{a523de0084bd4ba4b937533f88897371,
title = "Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes",
abstract = "AIMS: Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterised by progressive loss of motor neurons, muscle weakness, spasticity, paralysis and death usually within 2-5 years of onset. Neuroinflammation is a hallmark of ALS pathology characterized by activation of glial cells, which respond by upregulating small heat shock proteins (HSPBs), but the exact underlying pathological mechanisms are still largely unknown. Here, we investigated the association between ALS disease duration, lower motor neuron loss, TDP-43 pathology, neuroinflammation and HSPB expression.METHODS: With immunohistochemistry, we examined HSPB1, HSPB5, HSPB6, HSPB8 and HSP16.2 expression in cervical, thoracic and sacral spinal cord regions in 12 ALS cases, 7 with short disease duration (SDD), 5 with moderate disease duration (MDD), and 10 age-matched controls. Expression was quantified using ImageJ to examine HSP expression, motor neuron numbers, microglial and astrocyte density and pTDP-43+ inclusions.RESULTS: SDD was associated with elevated HSPB5 and 8 expression in lateral tract astrocytes, while HSP16.2 expression was increased in astrocytes in MDD cases. SDD cases had higher numbers of motor neurons and microglial activation than MDD cases, but similar levels of motor neurons with pTDP-43+ inclusions.CONCLUSIONS: Increased expression of several HSPBs in lateral column astrocytes suggests that astrocytes play a role in the pathogenesis of ALS. SDD is associated with increased microgliosis, HSPB5 and 8 expression in astrocytes, and only minor changes in motor neuron loss. This suggests that the interaction between motor neurons, microglia and astrocytes determines neuronal fate and functional decline in ALS. This article is protected by copyright. All rights reserved.",
keywords = "amyotrophic lateral sclerosis, astrocytes, HSPB, inflammation, small heat shock proteins, TDP-43 pathology, ALPHA-B-CRYSTALLIN, MULTIPLE-SCLEROSIS, STRESS-RESPONSE, MOUSE MODEL, DEGENERATION, ASTROGLIOSIS, AGGREGATION, PHENOTYPE, GLIOSIS, INDUCE",
author = "Gorter, {R. P.} and J. Stephenson and E. Nutma and J. Anink and {de Jonge}, {J. C.} and W. Baron and Jahreiss, {M. -C.} and Belien, {J. A. M.} and {van Noort}, {J. M.} and C. Mijnsbergen and E. Aronica and S. Amor",
note = "This article is protected by copyright. All rights reserved.",
year = "2019",
month = "8",
doi = "10.1111/nan.12525",
language = "English",
volume = "45",
pages = "459--475",
journal = "Neuropathology and Applied Neurobiology",
issn = "0305-1846",
publisher = "WILEY-BLACKWELL",
number = "5",

}

RIS

TY - JOUR

T1 - Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes

AU - Gorter, R. P.

AU - Stephenson, J.

AU - Nutma, E.

AU - Anink, J.

AU - de Jonge, J. C.

AU - Baron, W.

AU - Jahreiss, M. -C.

AU - Belien, J. A. M.

AU - van Noort, J. M.

AU - Mijnsbergen, C.

AU - Aronica, E.

AU - Amor, S.

N1 - This article is protected by copyright. All rights reserved.

PY - 2019/8

Y1 - 2019/8

N2 - AIMS: Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterised by progressive loss of motor neurons, muscle weakness, spasticity, paralysis and death usually within 2-5 years of onset. Neuroinflammation is a hallmark of ALS pathology characterized by activation of glial cells, which respond by upregulating small heat shock proteins (HSPBs), but the exact underlying pathological mechanisms are still largely unknown. Here, we investigated the association between ALS disease duration, lower motor neuron loss, TDP-43 pathology, neuroinflammation and HSPB expression.METHODS: With immunohistochemistry, we examined HSPB1, HSPB5, HSPB6, HSPB8 and HSP16.2 expression in cervical, thoracic and sacral spinal cord regions in 12 ALS cases, 7 with short disease duration (SDD), 5 with moderate disease duration (MDD), and 10 age-matched controls. Expression was quantified using ImageJ to examine HSP expression, motor neuron numbers, microglial and astrocyte density and pTDP-43+ inclusions.RESULTS: SDD was associated with elevated HSPB5 and 8 expression in lateral tract astrocytes, while HSP16.2 expression was increased in astrocytes in MDD cases. SDD cases had higher numbers of motor neurons and microglial activation than MDD cases, but similar levels of motor neurons with pTDP-43+ inclusions.CONCLUSIONS: Increased expression of several HSPBs in lateral column astrocytes suggests that astrocytes play a role in the pathogenesis of ALS. SDD is associated with increased microgliosis, HSPB5 and 8 expression in astrocytes, and only minor changes in motor neuron loss. This suggests that the interaction between motor neurons, microglia and astrocytes determines neuronal fate and functional decline in ALS. This article is protected by copyright. All rights reserved.

AB - AIMS: Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterised by progressive loss of motor neurons, muscle weakness, spasticity, paralysis and death usually within 2-5 years of onset. Neuroinflammation is a hallmark of ALS pathology characterized by activation of glial cells, which respond by upregulating small heat shock proteins (HSPBs), but the exact underlying pathological mechanisms are still largely unknown. Here, we investigated the association between ALS disease duration, lower motor neuron loss, TDP-43 pathology, neuroinflammation and HSPB expression.METHODS: With immunohistochemistry, we examined HSPB1, HSPB5, HSPB6, HSPB8 and HSP16.2 expression in cervical, thoracic and sacral spinal cord regions in 12 ALS cases, 7 with short disease duration (SDD), 5 with moderate disease duration (MDD), and 10 age-matched controls. Expression was quantified using ImageJ to examine HSP expression, motor neuron numbers, microglial and astrocyte density and pTDP-43+ inclusions.RESULTS: SDD was associated with elevated HSPB5 and 8 expression in lateral tract astrocytes, while HSP16.2 expression was increased in astrocytes in MDD cases. SDD cases had higher numbers of motor neurons and microglial activation than MDD cases, but similar levels of motor neurons with pTDP-43+ inclusions.CONCLUSIONS: Increased expression of several HSPBs in lateral column astrocytes suggests that astrocytes play a role in the pathogenesis of ALS. SDD is associated with increased microgliosis, HSPB5 and 8 expression in astrocytes, and only minor changes in motor neuron loss. This suggests that the interaction between motor neurons, microglia and astrocytes determines neuronal fate and functional decline in ALS. This article is protected by copyright. All rights reserved.

KW - amyotrophic lateral sclerosis

KW - astrocytes

KW - HSPB

KW - inflammation

KW - small heat shock proteins

KW - TDP-43 pathology

KW - ALPHA-B-CRYSTALLIN

KW - MULTIPLE-SCLEROSIS

KW - STRESS-RESPONSE

KW - MOUSE MODEL

KW - DEGENERATION

KW - ASTROGLIOSIS

KW - AGGREGATION

KW - PHENOTYPE

KW - GLIOSIS

KW - INDUCE

U2 - 10.1111/nan.12525

DO - 10.1111/nan.12525

M3 - Article

VL - 45

SP - 459

EP - 475

JO - Neuropathology and Applied Neurobiology

JF - Neuropathology and Applied Neurobiology

SN - 0305-1846

IS - 5

ER -

ID: 66614926