A longitudinal DTI and histological study of the spinal cord reveals early pathological alterations in G93A-SOD1 mouse model of amyotrophic lateral sclerosis

S Marcuzzo, S Bonanno, M Figini, Alessandro Scotti, I Zucca, L Minati, N Riva, Teuta Domi, A Fossaghi, A Quattrini, B Galbardi, S D'Alessandro, MG Bruzzone, JM García-Verdugo, V Moreno-Manzano, R Mantegazza, P Bernasconi

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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. © 2017 Elsevier Inc.
Original languageEnglish
Pages (from-to)43-52
Number of pages10
JournalExperimental Neurology
Volume293
Issue number4
DOIs
Publication statusPublished - 2017

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Amyotrophic Lateral Sclerosis
Spinal Cord
Motor Neurons
Histology
Nerve Degeneration
Diffusion Magnetic Resonance Imaging
Motor Cortex
Peripheral Nerves
Neurodegenerative Diseases
Brain Stem
Axons
Disease Progression
Electron Microscopy
White Matter

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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. / Marcuzzo, S; Bonanno, S; Figini, M; Scotti, Alessandro; Zucca, I; Minati, L; Riva, N; Domi, Teuta; Fossaghi, A; Quattrini, A; Galbardi, B; D'Alessandro, S; Bruzzone, MG; García-Verdugo, JM; Moreno-Manzano, V; Mantegazza, R; Bernasconi, P.

In: Experimental Neurology, Vol. 293, No. 4, 2017, p. 43-52.

Research output: Contribution to journalArticle

Marcuzzo, S ; Bonanno, S ; Figini, M ; Scotti, Alessandro ; Zucca, I ; Minati, L ; Riva, N ; Domi, Teuta ; Fossaghi, A ; Quattrini, A ; Galbardi, B ; D'Alessandro, S ; Bruzzone, MG ; García-Verdugo, JM ; Moreno-Manzano, V ; Mantegazza, R ; Bernasconi, P. / A longitudinal DTI and histological study of the spinal cord reveals early pathological alterations in G93A-SOD1 mouse model of amyotrophic lateral sclerosis. In: Experimental Neurology. 2017 ; Vol. 293, No. 4. pp. 43-52.
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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. {\circledC} 2017 Elsevier Inc.",
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AU - Bonanno, S

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AU - Scotti, Alessandro

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AB - 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. © 2017 Elsevier Inc.

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