title: Early and progressive impairment of spinal blood flow-glucose metabolism coupling in motor neuron degeneration of ALS model mice.
abstract: The exact mechanism of selective motor neuron death in amyotrophic lateral sclerosis (ALS) remains still unclear. In the present study, we performed in vivo capillary imaging, directly measured spinal blood flow (SBF) and glucose metabolism, and analyzed whether if a possible flow-metabolism coupling is disturbed in motor neuron degeneration of ALS model mice. In vivo capillary imaging showed progressive decrease of capillary diameter, capillary density, and red blood cell speed during the disease course. Spinal blood flow was progressively decreased in the anterior gray matter (GM) from presymptomatic stage to 0.80-fold of wild-type (WT) mice, 0.61 at early-symptomatic, and 0.49 at end stage of the disease. Local spinal glucose utilization (LSGU) was transiently increased to 1.19-fold in anterior GM at presymptomatic stage, which in turn progressively decreased to 0.84 and 0.60 at early-symptomatic and end stage of the disease. The LSGU/SBF ratio representing flow-metabolism uncoupling (FMU) preceded the sequential pathological changes in the spinal cord of ALS mice and was preferentially found in the affected region of ALS. The present study suggests that this early and progressive FMU could profoundly involve in the whole disease process as a vascular factor of ALS pathology, and could also be a potential target for therapeutic intervention of ALS.
authors: Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan.
authors: Kazunori
authors: K
authors: Miyazaki
authors: Kazuto
authors: K
authors: Masamoto
authors: Nobutoshi
authors: N
authors: Morimoto
authors: Tomoko
authors: T
authors: Kurata
authors: Takahumi
authors: T
authors: Mimoto
authors: Takayuki
authors: T
authors: Obata
authors: Iwao
authors: I
authors: Kanno
authors: Koji
authors: K
authors: Abe
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002196:Capillaries / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration; D012039:Regional Blood Flow / Q000502:physiology; D013116:Spinal Cord / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005947:Glucose