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

作者：Marcuzzo Stefania; Bonanno Silvia; Figini Matteo; Scotti Alessandro; Zucca Ileana; Minati Ludovico; Riva Nilo; Domi Teuta; Fossaghi Andrea; Quattrini Angelo; Galbardi Barbara; D'Alessandro Sara; Grazia Bruzzone Maria; Manuel Garcia Verdugo Jose; Moreno Manzano Victoria; Mantegazza Renato; Bernasconi Pia^*

来源：Experimental Neurology, 2017, 293: 43-52.

DOI：10.1016/j.expneurol.2017.03.018

• Amyotrophic lateral sclerosis
• G93A-SOD1 mice
• Magnetic resonance imaging
• Electron microscopy
• Axon degeneration
• Motor neuron diseases

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.

• 出版日期2017-7