title: A longitudinal DTI and histological study of the spinal cord reveals early pathological alterations in G93A-SOD1 mouse model of amyotrophic lateral sclerosis.
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.affiliation: Neurology IV -Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Marcuzzo
authors.affiliation: 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.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bonanno
authors.affiliation: Scientific Department, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Figini
authors.affiliation: Scientific Department, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Scotti
authors.affiliation: Scientific Department, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.
authors.forename: Ileana
authors.initials: I
authors.lastname: Zucca
authors.affiliation: Scientific Department, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.
authors.forename: Ludovico
authors.initials: L
authors.lastname: Minati
authors.affiliation: Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy.
authors.forename: Nilo
authors.initials: N
authors.lastname: Riva
authors.affiliation: Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy.
authors.forename: Teuta
authors.initials: T
authors.lastname: Domi
authors.affiliation: Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fossaghi
authors.affiliation: Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Quattrini
authors.affiliation: Scientific Department, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Galbardi
authors.affiliation: Neurology IV -Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: D'Alessandro
authors.affiliation: Neuroradiology, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Bruzzone
authors.affiliation: Unidad de Neurobiología comparada, Universidad de Valencia, Paterna, Valencia 46980, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: García-Verdugo
authors.affiliation: Neuronal and Tissue Regeneration Laboratory, Centro de Investigación Príncipe Felipe, Valencia 46012, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Moreno-Manzano
authors.affiliation: Neurology IV -Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Mantegazza
authors.affiliation: Neurology IV -Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico "Carlo Besta", Milan 20133, Italy. Electronic address: pia.bernasconi@istituto-besta.it.
authors.forename: Pia
authors.initials: P
authors.lastname: Bernasconi
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000000981:diagnostic imaging* / Q000235:genetics*; D000818:Animals; D000873:Anthracenes; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000648:ultrastructure; D006801:Humans; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure; D011984:Sensory Receptor Cells / Q000473:pathology / Q000648:ultrastructure; D013116:Spinal Cord / Q000000981:diagnostic imaging* / Q000473:pathology / Q000648:ultrastructure; D013482:Superoxide Dismutase / Q000235:genetics*; D013997:Time Factors; D066127:White Matter / Q000000981:diagnostic imaging / Q000648:ultrastructure
chemical_list: C546739:AnOV compound; D000873:Anthracenes; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase
keywords: Amyotrophic lateral sclerosis; Axon degeneration; Electron microscopy; G93A-SOD1 mice; Magnetic resonance imaging; Motor neuron diseases