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Spinal manifestations of CLN1 disease start during the early postnatal period

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Spinal manifestations of CLN1 disease start during the early postnatal period. / Nelvagal, H R; Dearborn, J T; Ostergaard, J R; Sands, M S; Cooper, J D.

In: Neuropathology and Applied Neurobiology, Vol. 47, No. 2, 02.2021.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Nelvagal, HR, Dearborn, JT, Ostergaard, JR, Sands, MS & Cooper, JD 2021, 'Spinal manifestations of CLN1 disease start during the early postnatal period', Neuropathology and Applied Neurobiology, vol. 47, no. 2. https://doi.org/10.1111/nan.12658

APA

Nelvagal, H. R., Dearborn, J. T., Ostergaard, J. R., Sands, M. S., & Cooper, J. D. (2021). Spinal manifestations of CLN1 disease start during the early postnatal period. Neuropathology and Applied Neurobiology, 47(2). https://doi.org/10.1111/nan.12658

CBE

Nelvagal HR, Dearborn JT, Ostergaard JR, Sands MS, Cooper JD. 2021. Spinal manifestations of CLN1 disease start during the early postnatal period. Neuropathology and Applied Neurobiology. 47(2). https://doi.org/10.1111/nan.12658

MLA

Nelvagal, H R et al. "Spinal manifestations of CLN1 disease start during the early postnatal period". Neuropathology and Applied Neurobiology. 2021. 47(2). https://doi.org/10.1111/nan.12658

Vancouver

Nelvagal HR, Dearborn JT, Ostergaard JR, Sands MS, Cooper JD. Spinal manifestations of CLN1 disease start during the early postnatal period. Neuropathology and Applied Neurobiology. 2021 Feb;47(2). https://doi.org/10.1111/nan.12658

Author

Nelvagal, H R ; Dearborn, J T ; Ostergaard, J R ; Sands, M S ; Cooper, J D. / Spinal manifestations of CLN1 disease start during the early postnatal period. In: Neuropathology and Applied Neurobiology. 2021 ; Vol. 47, No. 2.

Bibtex

@article{66c493d8efe14ca4b9ceff7b6d59f7c0,
title = "Spinal manifestations of CLN1 disease start during the early postnatal period",
abstract = "AIM: To understand the progression of CLN1 disease and develop effective therapies we need to characterize early sites of pathology. Therefore, we performed a comprehensive evaluation of the nature and timing of early CLN1 disease pathology in the spinal cord, which appears especially vulnerable, and how this may affect behaviour.METHODS: We measured the spinal volume and neuronal number, and quantified glial activation, lymphocyte infiltration and oligodendrocyte maturation, as well as cytokine profile analysis during the early stages of pathology in Ppt1-deficient (Ppt1-/- ) mouse spinal cords. We then performed quantitative gait analysis and open-field behaviour tests to investigate the behavioural correlates during this period.RESULTS: We detected significant microglial activation in Ppt1-/- spinal cords at 1 month. This was followed by astrocytosis, selective interneuron loss, altered spinal volumes and oligodendrocyte maturation at 2 months, before significant storage material accumulation and lymphocyte infiltration at 3 months. The same time course was apparent for inflammatory cytokine expression that was altered as early as one month. There was a transient early period at 2 months when Ppt1-/- mice had a significantly altered gait that resembles the presentation in children with CLN1 disease. This occurred before an anticipated decline in overall locomotor performance across all ages.CONCLUSION: These data reveal disease onset 2 months (25% of life-span) earlier than expected, while spinal maturation is still ongoing. Our multi-disciplinary data provide new insights into the spatio-temporal staging of CLN1 pathogenesis during ongoing postnatal maturation, and highlight the need to deliver therapies during the presymptomatic period.",
keywords = "ACTIVATION, BRAIN, CORD, EXPRESSION, GAIT ANALYSIS, INFANTILE TYPE, MOUSE MODELS, NEURONAL CEROID-LIPOFUSCINOSIS, PATHOLOGY, SURVIVAL, batten disease, gait, neurodegeneration, neuronal ceroid lipofuscinosis, postnatal development, spinal cord",
author = "Nelvagal, {H R} and Dearborn, {J T} and Ostergaard, {J R} and Sands, {M S} and Cooper, {J D}",
note = "{\textcopyright} 2020 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.",
year = "2021",
month = feb,
doi = "10.1111/nan.12658",
language = "English",
volume = "47",
journal = "Neuropathology and Applied Neurobiology",
issn = "0305-1846",
publisher = "Wiley-Blackwell Publishing Ltd.",
number = "2",

}

RIS

TY - JOUR

T1 - Spinal manifestations of CLN1 disease start during the early postnatal period

AU - Nelvagal, H R

AU - Dearborn, J T

AU - Ostergaard, J R

AU - Sands, M S

AU - Cooper, J D

N1 - © 2020 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

PY - 2021/2

Y1 - 2021/2

N2 - AIM: To understand the progression of CLN1 disease and develop effective therapies we need to characterize early sites of pathology. Therefore, we performed a comprehensive evaluation of the nature and timing of early CLN1 disease pathology in the spinal cord, which appears especially vulnerable, and how this may affect behaviour.METHODS: We measured the spinal volume and neuronal number, and quantified glial activation, lymphocyte infiltration and oligodendrocyte maturation, as well as cytokine profile analysis during the early stages of pathology in Ppt1-deficient (Ppt1-/- ) mouse spinal cords. We then performed quantitative gait analysis and open-field behaviour tests to investigate the behavioural correlates during this period.RESULTS: We detected significant microglial activation in Ppt1-/- spinal cords at 1 month. This was followed by astrocytosis, selective interneuron loss, altered spinal volumes and oligodendrocyte maturation at 2 months, before significant storage material accumulation and lymphocyte infiltration at 3 months. The same time course was apparent for inflammatory cytokine expression that was altered as early as one month. There was a transient early period at 2 months when Ppt1-/- mice had a significantly altered gait that resembles the presentation in children with CLN1 disease. This occurred before an anticipated decline in overall locomotor performance across all ages.CONCLUSION: These data reveal disease onset 2 months (25% of life-span) earlier than expected, while spinal maturation is still ongoing. Our multi-disciplinary data provide new insights into the spatio-temporal staging of CLN1 pathogenesis during ongoing postnatal maturation, and highlight the need to deliver therapies during the presymptomatic period.

AB - AIM: To understand the progression of CLN1 disease and develop effective therapies we need to characterize early sites of pathology. Therefore, we performed a comprehensive evaluation of the nature and timing of early CLN1 disease pathology in the spinal cord, which appears especially vulnerable, and how this may affect behaviour.METHODS: We measured the spinal volume and neuronal number, and quantified glial activation, lymphocyte infiltration and oligodendrocyte maturation, as well as cytokine profile analysis during the early stages of pathology in Ppt1-deficient (Ppt1-/- ) mouse spinal cords. We then performed quantitative gait analysis and open-field behaviour tests to investigate the behavioural correlates during this period.RESULTS: We detected significant microglial activation in Ppt1-/- spinal cords at 1 month. This was followed by astrocytosis, selective interneuron loss, altered spinal volumes and oligodendrocyte maturation at 2 months, before significant storage material accumulation and lymphocyte infiltration at 3 months. The same time course was apparent for inflammatory cytokine expression that was altered as early as one month. There was a transient early period at 2 months when Ppt1-/- mice had a significantly altered gait that resembles the presentation in children with CLN1 disease. This occurred before an anticipated decline in overall locomotor performance across all ages.CONCLUSION: These data reveal disease onset 2 months (25% of life-span) earlier than expected, while spinal maturation is still ongoing. Our multi-disciplinary data provide new insights into the spatio-temporal staging of CLN1 pathogenesis during ongoing postnatal maturation, and highlight the need to deliver therapies during the presymptomatic period.

KW - ACTIVATION

KW - BRAIN

KW - CORD

KW - EXPRESSION

KW - GAIT ANALYSIS

KW - INFANTILE TYPE

KW - MOUSE MODELS

KW - NEURONAL CEROID-LIPOFUSCINOSIS

KW - PATHOLOGY

KW - SURVIVAL

KW - batten disease

KW - gait

KW - neurodegeneration

KW - neuronal ceroid lipofuscinosis

KW - postnatal development

KW - spinal cord

U2 - 10.1111/nan.12658

DO - 10.1111/nan.12658

M3 - Journal article

C2 - 32841420

VL - 47

JO - Neuropathology and Applied Neurobiology

JF - Neuropathology and Applied Neurobiology

SN - 0305-1846

IS - 2

ER -