Longitudinal monitoring of motor neuron circuitry in FALS rats using in-vivo phMRI.
Amyotrophic lateral sclerosis (ALS) presents challenges for diagnosis and objective monitoring of disease progression. We show, using pharmacologic MRI, that alterations in motor circuitry can be characterized using a passive stimulus in a rat model of familial ALS as a function of symptom progression. Presymptomatic familial ALS rats had a pattern of activation to amphetamine that was statistically indistinguishable from the wild-type controls. In contrast, symptomatic rats showed significantly decreased response in sensorimotor cortex and increased response in M2 motor cortex, caudate/putamen, and thalamus. These results are similar to findings in humans of altered response to motor tasks in ALS. It may be plausible to use a passive amphetamine challenge as a biomarker to assess progression of the disease and efficacy of potential treatments.
Choi
Ji-Kyung
JK
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Dedeoglu
Alpaslan
A
Jenkins
Bruce G
BG
D000661:Amphetamine / Q000494:pharmacology*; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001931:Brain Mapping; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging; D008297:Male; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
D000697:Central Nervous System Stimulants; D000661:Amphetamine