6533b825fe1ef96bd128284f
RESEARCH PRODUCT
A longitudinal DTI and histological study of the spinal cord reveals early pathological alterations in G93A-SOD1 mouse model of amyotrophic lateral sclerosis.
Silvia BonannoBarbara GalbardiIleana ZuccaSara D’alessandroJosé Manuel García-verdugoAlessandro ScottiRenato MantegazzaMaria Grazia BruzzoneAndrea FossaghiNilo RivaAngelo QuattriniVictoria Moreno-manzanoMatteo FiginiTeuta DomiStefania MarcuzzoPia BernasconiLudovico Minatisubject
0301 basic medicinePathologyNeurologyTime FactorsMotor neuron diseasesSensory Receptor CellMice0302 clinical medicineImage Processing Computer-AssistedAxonAmyotrophic lateral sclerosisGray MatterAnthracenesWhite MatterMitochondriamedicine.anatomical_structureDiffusion Tensor ImagingNeurologySpinal CordG93A-SOD1 miceBrainstemHumanMotor cortexmedicine.medical_specialtyAxon degenerationTime FactorSensory Receptor CellsSOD1Mice TransgenicWhite matter03 medical and health sciencesMagnetic resonance imagingDevelopmental NeuroscienceMicroscopy Electron TransmissionmedicineElectron microscopyAnimalsHumansMotor neuron diseaseAmyotrophic lateral sclerosiAnimalbusiness.industrySuperoxide DismutaseAmyotrophic Lateral SclerosisSpinal cordmedicine.diseaseAmyotrophic lateral sclerosisMice Inbred C57BLDisease Models Animal030104 developmental biologyAnthracenebusinessNeuroscience030217 neurology & neurosurgerydescription
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 AIS 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. (C) 2017 Elsevier Inc. All rights reserved.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-01-01 | Experimental neurology |