Increased Axon Initial Segment Length Results in Increased Na+ Currents in Spinal Motoneurones at Symptom Onset in the G127X SOD1 Mouse Model of Amyotrophic Lateral Sclerosis

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Increased Axon Initial Segment Length Results in Increased Na+ Currents in Spinal Motoneurones at Symptom Onset in the G127X SOD1 Mouse Model of Amyotrophic Lateral Sclerosis. / Jørgensen, H. S.; Jensen, D. B.; Dimintiyanova, K. P.; Bonnevie, V. S.; Hedegaard, A.; Lehnhoff, J.; Moldovan, M.; Grondahl, L.; Meehan, C. F.

In: Neuroscience, Vol. 468, 2021, p. 247-264.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Jørgensen, HS, Jensen, DB, Dimintiyanova, KP, Bonnevie, VS, Hedegaard, A, Lehnhoff, J, Moldovan, M, Grondahl, L & Meehan, CF 2021, 'Increased Axon Initial Segment Length Results in Increased Na+ Currents in Spinal Motoneurones at Symptom Onset in the G127X SOD1 Mouse Model of Amyotrophic Lateral Sclerosis', Neuroscience, vol. 468, pp. 247-264. https://doi.org/10.1016/j.neuroscience.2020.11.016

APA

Jørgensen, H. S., Jensen, D. B., Dimintiyanova, K. P., Bonnevie, V. S., Hedegaard, A., Lehnhoff, J., Moldovan, M., Grondahl, L., & Meehan, C. F. (2021). Increased Axon Initial Segment Length Results in Increased Na+ Currents in Spinal Motoneurones at Symptom Onset in the G127X SOD1 Mouse Model of Amyotrophic Lateral Sclerosis. Neuroscience, 468, 247-264. https://doi.org/10.1016/j.neuroscience.2020.11.016

Vancouver

Jørgensen HS, Jensen DB, Dimintiyanova KP, Bonnevie VS, Hedegaard A, Lehnhoff J et al. Increased Axon Initial Segment Length Results in Increased Na+ Currents in Spinal Motoneurones at Symptom Onset in the G127X SOD1 Mouse Model of Amyotrophic Lateral Sclerosis. Neuroscience. 2021;468:247-264. https://doi.org/10.1016/j.neuroscience.2020.11.016

Author

Jørgensen, H. S. ; Jensen, D. B. ; Dimintiyanova, K. P. ; Bonnevie, V. S. ; Hedegaard, A. ; Lehnhoff, J. ; Moldovan, M. ; Grondahl, L. ; Meehan, C. F. / Increased Axon Initial Segment Length Results in Increased Na+ Currents in Spinal Motoneurones at Symptom Onset in the G127X SOD1 Mouse Model of Amyotrophic Lateral Sclerosis. In: Neuroscience. 2021 ; Vol. 468. pp. 247-264.

Bibtex

@article{b9eefe46013e4580bd24128d3bfef7c0,
title = "Increased Axon Initial Segment Length Results in Increased Na+ Currents in Spinal Motoneurones at Symptom Onset in the G127X SOD1 Mouse Model of Amyotrophic Lateral Sclerosis",
abstract = "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease preferentially affecting motoneurones. Transgenic mouse models have been used to investigate the role of abnormal motoneurone excitability in this disease. Whilst an increased excitability has repeatedly been demonstrated in vitro in neonatal and embryonic preparations from SOD1 mouse models, the results from the only studies to record in vivo from spinal motoneurones in adult SOD1 models have produced conflicting findings. Deficits in repetitive firing have been reported in G93A SOD1((high copy number)) mice but not in presymptomatic G127X SOD1 mice despite shorter motoneurone axon initial segments (AISs) in these mice. These discrepancies may be due to the earlier disease onset and prolonged disease progression in G93A SOD1 mice with recordings potentially performed at a later sub-clinical stage of the disease in this mouse. To test this, and to explore how the evolution of excitability changes with symptom onset we performed in vivo intracellular recording and AIS labelling in G127X SOD1 mice immediately after symptom onset. No reductions in repetitive firing were observed showing that this is not a common feature across all ALS models. Immunohistochemistry for the Na+ channel Nav1.6 showed that motoneurone AISs increase in length in G127X SOD1 mice at symptom onset. Consistent with this, the rate of rise of AIS components of antidromic action potentials were significantly faster confirming that this increase in length represents an increase in AIS Na+ channels occurring at symptom onset in this model. (C) 2020 Published by Elsevier Ltd on behalf of IBRO.",
keywords = "Na+ channels, axon initial segment, ALS, ACTIVITY-DEPENDENT RELOCATION, MOTOR UNIT LOSS, EXCITABILITY CHANGES, SYNAPTIC-TRANSMISSION, ELECTRICAL-PROPERTIES, LUMBAR MOTONEURONS, CORD-INJURY, TIME-COURSE, RILUZOLE, ASTROCYTES",
author = "J{\o}rgensen, {H. S.} and Jensen, {D. B.} and Dimintiyanova, {K. P.} and Bonnevie, {V. S.} and A. Hedegaard and J. Lehnhoff and M. Moldovan and L. Grondahl and Meehan, {C. F.}",
year = "2021",
doi = "10.1016/j.neuroscience.2020.11.016",
language = "English",
volume = "468",
pages = "247--264",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Pergamon Press",

}

RIS

TY - JOUR

T1 - Increased Axon Initial Segment Length Results in Increased Na+ Currents in Spinal Motoneurones at Symptom Onset in the G127X SOD1 Mouse Model of Amyotrophic Lateral Sclerosis

AU - Jørgensen, H. S.

AU - Jensen, D. B.

AU - Dimintiyanova, K. P.

AU - Bonnevie, V. S.

AU - Hedegaard, A.

AU - Lehnhoff, J.

AU - Moldovan, M.

AU - Grondahl, L.

AU - Meehan, C. F.

PY - 2021

Y1 - 2021

N2 - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease preferentially affecting motoneurones. Transgenic mouse models have been used to investigate the role of abnormal motoneurone excitability in this disease. Whilst an increased excitability has repeatedly been demonstrated in vitro in neonatal and embryonic preparations from SOD1 mouse models, the results from the only studies to record in vivo from spinal motoneurones in adult SOD1 models have produced conflicting findings. Deficits in repetitive firing have been reported in G93A SOD1((high copy number)) mice but not in presymptomatic G127X SOD1 mice despite shorter motoneurone axon initial segments (AISs) in these mice. These discrepancies may be due to the earlier disease onset and prolonged disease progression in G93A SOD1 mice with recordings potentially performed at a later sub-clinical stage of the disease in this mouse. To test this, and to explore how the evolution of excitability changes with symptom onset we performed in vivo intracellular recording and AIS labelling in G127X SOD1 mice immediately after symptom onset. No reductions in repetitive firing were observed showing that this is not a common feature across all ALS models. Immunohistochemistry for the Na+ channel Nav1.6 showed that motoneurone AISs increase in length in G127X SOD1 mice at symptom onset. Consistent with this, the rate of rise of AIS components of antidromic action potentials were significantly faster confirming that this increase in length represents an increase in AIS Na+ channels occurring at symptom onset in this model. (C) 2020 Published by Elsevier Ltd on behalf of IBRO.

AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease preferentially affecting motoneurones. Transgenic mouse models have been used to investigate the role of abnormal motoneurone excitability in this disease. Whilst an increased excitability has repeatedly been demonstrated in vitro in neonatal and embryonic preparations from SOD1 mouse models, the results from the only studies to record in vivo from spinal motoneurones in adult SOD1 models have produced conflicting findings. Deficits in repetitive firing have been reported in G93A SOD1((high copy number)) mice but not in presymptomatic G127X SOD1 mice despite shorter motoneurone axon initial segments (AISs) in these mice. These discrepancies may be due to the earlier disease onset and prolonged disease progression in G93A SOD1 mice with recordings potentially performed at a later sub-clinical stage of the disease in this mouse. To test this, and to explore how the evolution of excitability changes with symptom onset we performed in vivo intracellular recording and AIS labelling in G127X SOD1 mice immediately after symptom onset. No reductions in repetitive firing were observed showing that this is not a common feature across all ALS models. Immunohistochemistry for the Na+ channel Nav1.6 showed that motoneurone AISs increase in length in G127X SOD1 mice at symptom onset. Consistent with this, the rate of rise of AIS components of antidromic action potentials were significantly faster confirming that this increase in length represents an increase in AIS Na+ channels occurring at symptom onset in this model. (C) 2020 Published by Elsevier Ltd on behalf of IBRO.

KW - Na+ channels

KW - axon initial segment

KW - ALS

KW - ACTIVITY-DEPENDENT RELOCATION

KW - MOTOR UNIT LOSS

KW - EXCITABILITY CHANGES

KW - SYNAPTIC-TRANSMISSION

KW - ELECTRICAL-PROPERTIES

KW - LUMBAR MOTONEURONS

KW - CORD-INJURY

KW - TIME-COURSE

KW - RILUZOLE

KW - ASTROCYTES

U2 - 10.1016/j.neuroscience.2020.11.016

DO - 10.1016/j.neuroscience.2020.11.016

M3 - Journal article

C2 - 33246068

VL - 468

SP - 247

EP - 264

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

ER -

ID: 275323865