Early and progressive impairment of spinal blood flow-glucose metabolism coupling in motor neuron degeneration of ALS model mice

Kazunori Miyazaki, Kazuto Masamoto, Nobutoshi Morimoto, Tomoko Kurata, Takahumi Mimoto, Takayuki Obata, Iwao Kanno, Koji Abe

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)456-467
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume32
Issue number3
DOIs
Publication statusPublished - Mar 2012

Fingerprint

Nerve Degeneration
Amyotrophic Lateral Sclerosis
Motor Neurons
Blood Glucose
Glucose
Spinal Cord
Erythrocytes
Pathology

Keywords

  • ALS
  • flow-metabolism uncoupling (FMU)
  • G93A
  • local spinal glucose utilization (LSGU)
  • spinal blood flow (SBF)

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

Cite this

Early and progressive impairment of spinal blood flow-glucose metabolism coupling in motor neuron degeneration of ALS model mice. / Miyazaki, Kazunori; Masamoto, Kazuto; Morimoto, Nobutoshi; Kurata, Tomoko; Mimoto, Takahumi; Obata, Takayuki; Kanno, Iwao; Abe, Koji.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 32, No. 3, 03.2012, p. 456-467.

Research output: Contribution to journalArticle

Miyazaki, Kazunori ; Masamoto, Kazuto ; Morimoto, Nobutoshi ; Kurata, Tomoko ; Mimoto, Takahumi ; Obata, Takayuki ; Kanno, Iwao ; Abe, Koji. / Early and progressive impairment of spinal blood flow-glucose metabolism coupling in motor neuron degeneration of ALS model mice. In: Journal of Cerebral Blood Flow and Metabolism. 2012 ; Vol. 32, No. 3. pp. 456-467.
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