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Size-Dependent Vulnerability of Lumbar Motor Neuron Dendritic Degeneration in SOD1G93A Mice.

Abstract

The motor neuron (MN) soma surface area is correlated with motor unit type. Larger MNs innervate fast fatigue-intermediate (FInt) or fast-fatiguable (FF) muscle fibers in type FInt and FF motor units, respectively. Smaller MNs innervate slow-twitch fatigue-resistant (S) or fast fatigue-resistant (FR) muscle fibers in type S and FR motor units, respectively. In amyotrophic lateral sclerosis (ALS), FInt and FF motor units are more vulnerable, with denervation and MN death occurring for these units before the more resilient S and FR units. Abnormal MN dendritic arbors have been observed in ALS in humans and rodent models. We used a Golgi-Cox impregnation protocol to examine soma size-dependent changes in the dendritic morphology of lumbar MNs in SOD1G93A mice, a model of ALS, at pre-symptomatic, onset and mid-disease stages. In wildtype control mice, the relationship between MN soma surface area and dendritic length or dendritic spine number was highly linear (i.e., increased MN soma size correlated with increased dendritic length and spines). By contrast, in SOD1G93A mice, this linear relationship was lost and dendritic length reduction and spine loss were observed in larger MNs, from pre-symptomatic stages onward. These changes correlated with the neuromotor symptoms of ALS in rodent models. At presymptomatic ages, changes were restricted to the larger MNs, likely to comprise vulnerable FInt and FF motor units. Our results suggest morphological changes of MN dendrites and dendritic spines are likely to contribute ALS pathogenesis, not compensate for it. Anat Rec, 2019. © 2019 American Association for Anatomy.

Authors+Show Affiliations

School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia. Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia.School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia.School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia. Queensland Brain Institute, The University of Queensland, St Lucia, Queensland, Australia.School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31509351

Citation

Fogarty, Matthew J., et al. "Size-Dependent Vulnerability of Lumbar Motor Neuron Dendritic Degeneration in SOD1G93A Mice." Anatomical Record (Hoboken, N.J. : 2007), 2019.
Fogarty MJ, Mu EWH, Lavidis NA, et al. Size-Dependent Vulnerability of Lumbar Motor Neuron Dendritic Degeneration in SOD1G93A Mice. Anat Rec (Hoboken). 2019.
Fogarty, M. J., Mu, E. W. H., Lavidis, N. A., Noakes, P. G., & Bellingham, M. C. (2019). Size-Dependent Vulnerability of Lumbar Motor Neuron Dendritic Degeneration in SOD1G93A Mice. Anatomical Record (Hoboken, N.J. : 2007), doi:10.1002/ar.24255.
Fogarty MJ, et al. Size-Dependent Vulnerability of Lumbar Motor Neuron Dendritic Degeneration in SOD1G93A Mice. Anat Rec (Hoboken). 2019 Sep 11; PubMed PMID: 31509351.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Size-Dependent Vulnerability of Lumbar Motor Neuron Dendritic Degeneration in SOD1G93A Mice. AU - Fogarty,Matthew J, AU - Mu,Erica W H, AU - Lavidis,Nickolas A, AU - Noakes,Peter G, AU - Bellingham,Mark C, Y1 - 2019/09/11/ PY - 2019/03/09/received PY - 2019/05/22/revised PY - 2019/06/29/accepted PY - 2019/9/12/pubmed PY - 2019/9/12/medline PY - 2019/9/12/entrez KW - SOD1G93A mouse KW - amyotrophic lateral sclerosis KW - dendrite KW - dendritic spine KW - motor neuron disease JF - Anatomical record (Hoboken, N.J. : 2007) JO - Anat Rec (Hoboken) N2 - The motor neuron (MN) soma surface area is correlated with motor unit type. Larger MNs innervate fast fatigue-intermediate (FInt) or fast-fatiguable (FF) muscle fibers in type FInt and FF motor units, respectively. Smaller MNs innervate slow-twitch fatigue-resistant (S) or fast fatigue-resistant (FR) muscle fibers in type S and FR motor units, respectively. In amyotrophic lateral sclerosis (ALS), FInt and FF motor units are more vulnerable, with denervation and MN death occurring for these units before the more resilient S and FR units. Abnormal MN dendritic arbors have been observed in ALS in humans and rodent models. We used a Golgi-Cox impregnation protocol to examine soma size-dependent changes in the dendritic morphology of lumbar MNs in SOD1G93A mice, a model of ALS, at pre-symptomatic, onset and mid-disease stages. In wildtype control mice, the relationship between MN soma surface area and dendritic length or dendritic spine number was highly linear (i.e., increased MN soma size correlated with increased dendritic length and spines). By contrast, in SOD1G93A mice, this linear relationship was lost and dendritic length reduction and spine loss were observed in larger MNs, from pre-symptomatic stages onward. These changes correlated with the neuromotor symptoms of ALS in rodent models. At presymptomatic ages, changes were restricted to the larger MNs, likely to comprise vulnerable FInt and FF motor units. Our results suggest morphological changes of MN dendrites and dendritic spines are likely to contribute ALS pathogenesis, not compensate for it. Anat Rec, 2019. © 2019 American Association for Anatomy. SN - 1932-8494 UR - https://www.unboundmedicine.com/medline/citation/31509351/Size-dependent_vulnerability_of_lumbar_motor_neuron_dendritic_degeneration_in_SOD1G93A_mice L2 - https://doi.org/10.1002/ar.24255 DB - PRIME DP - Unbound Medicine ER -