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A longitudinal DTI and histological study of the spinal cord reveals early pathological alterations in G93A-SOD1 mouse model of amyotrophic lateral sclerosis.
Exp Neurol. 2017 07; 293:43-52.EN

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective motor neuron degeneration in the motor cortex, brainstem and spinal cord. It is generally accepted that ALS is caused by death of motor neurons, however the exact temporal cascade of degenerative processes is not yet completely known. To identify the early pathological changes in spinal cord of G93A-SOD1 ALS mice we performed a comprehensive longitudinal analysis employing diffusion-tensor magnetic resonance imaging alongside histology and electron microscopy, in parallel with peripheral nerve histology. We showed the gradient of degeneration appearance in spinal cord white and gray matter, starting earliest in the ventral white matter, due to a cascade of pathological events including axon dysfunction and mitochondrial changes. Notably, we found that even the main sensory regions are affected by the neurodegenerative process at symptomatic disease phase. Overall our results attest the applicability of DTI in determining disease progression in ALS mice. These findings suggest that DTI could be potentially adapted in humans to aid the assessment of ALS progression and eventually the evaluation of treatment efficacy.

Authors+Show Affiliations

Neurology IV -Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.Neurology IV -Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy; PhD Program in Neuroscience, University of Milano-Bicocca, Milan 20126, Italy.Scientific Department, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.Scientific Department, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.Scientific Department, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.Scientific Department, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy.Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy.Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy.Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy.Scientific Department, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.Neurology IV -Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.Neuroradiology, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.Unidad de Neurobiología comparada, Universidad de Valencia, Paterna, Valencia 46980, Spain.Neuronal and Tissue Regeneration Laboratory, Centro de Investigación Príncipe Felipe, Valencia 46012, Spain.Neurology IV -Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.Neurology IV -Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy. Electronic address: pia.bernasconi@istituto-besta.it.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28351750

Citation

Marcuzzo, Stefania, et al. "A Longitudinal DTI and Histological Study of the Spinal Cord Reveals Early Pathological Alterations in G93A-SOD1 Mouse Model of Amyotrophic Lateral Sclerosis." Experimental Neurology, vol. 293, 2017, pp. 43-52.
Marcuzzo S, Bonanno S, Figini M, et al. A longitudinal DTI and histological study of the spinal cord reveals early pathological alterations in G93A-SOD1 mouse model of amyotrophic lateral sclerosis. Exp Neurol. 2017;293:43-52.
Marcuzzo, S., Bonanno, S., Figini, M., Scotti, A., Zucca, I., Minati, L., Riva, N., Domi, T., Fossaghi, A., Quattrini, A., Galbardi, B., D'Alessandro, S., Bruzzone, M. G., García-Verdugo, J. M., Moreno-Manzano, V., Mantegazza, R., & Bernasconi, P. (2017). A longitudinal DTI and histological study of the spinal cord reveals early pathological alterations in G93A-SOD1 mouse model of amyotrophic lateral sclerosis. Experimental Neurology, 293, 43-52. https://doi.org/10.1016/j.expneurol.2017.03.018
Marcuzzo S, et al. A Longitudinal DTI and Histological Study of the Spinal Cord Reveals Early Pathological Alterations in G93A-SOD1 Mouse Model of Amyotrophic Lateral Sclerosis. Exp Neurol. 2017;293:43-52. PubMed PMID: 28351750.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A longitudinal DTI and histological study of the spinal cord reveals early pathological alterations in G93A-SOD1 mouse model of amyotrophic lateral sclerosis. AU - Marcuzzo,Stefania, AU - Bonanno,Silvia, AU - Figini,Matteo, AU - Scotti,Alessandro, AU - Zucca,Ileana, AU - Minati,Ludovico, AU - Riva,Nilo, AU - Domi,Teuta, AU - Fossaghi,Andrea, AU - Quattrini,Angelo, AU - Galbardi,Barbara, AU - D'Alessandro,Sara, AU - Bruzzone,Maria Grazia, AU - García-Verdugo,José Manuel, AU - Moreno-Manzano,Victoria, AU - Mantegazza,Renato, AU - Bernasconi,Pia, Y1 - 2017/03/27/ PY - 2016/09/30/received PY - 2017/03/02/revised PY - 2017/03/24/accepted PY - 2017/3/30/pubmed PY - 2017/8/18/medline PY - 2017/3/30/entrez KW - Amyotrophic lateral sclerosis KW - Axon degeneration KW - Electron microscopy KW - G93A-SOD1 mice KW - Magnetic resonance imaging KW - Motor neuron diseases SP - 43 EP - 52 JF - Experimental neurology JO - Exp. Neurol. VL - 293 N2 - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective motor neuron degeneration in the motor cortex, brainstem and spinal cord. It is generally accepted that ALS is caused by death of motor neurons, however the exact temporal cascade of degenerative processes is not yet completely known. To identify the early pathological changes in spinal cord of G93A-SOD1 ALS mice we performed a comprehensive longitudinal analysis employing diffusion-tensor magnetic resonance imaging alongside histology and electron microscopy, in parallel with peripheral nerve histology. We showed the gradient of degeneration appearance in spinal cord white and gray matter, starting earliest in the ventral white matter, due to a cascade of pathological events including axon dysfunction and mitochondrial changes. Notably, we found that even the main sensory regions are affected by the neurodegenerative process at symptomatic disease phase. Overall our results attest the applicability of DTI in determining disease progression in ALS mice. These findings suggest that DTI could be potentially adapted in humans to aid the assessment of ALS progression and eventually the evaluation of treatment efficacy. SN - 1090-2430 UR - https://www.unboundmedicine.com/medline/citation/28351750/A_longitudinal_DTI_and_histological_study_of_the_spinal_cord_reveals_early_pathological_alterations_in_G93A_SOD1_mouse_model_of_amyotrophic_lateral_sclerosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(17)30078-X DB - PRIME DP - Unbound Medicine ER -