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Neurobiol Dis. 2010 Sep;39(3):252-64. doi: 10.1016/j.nbd.2010.03.021. Epub 2010 Apr 8.

Peripheral hyperstimulation alters site of disease onset and course in SOD1 rats.

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1
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

In amyotrophic lateral sclerosis (ALS), the exogenous temporal triggers that result in initial motor neuron death are not understood. Overactivation and consequent accelerated loss of vulnerable motor neurons is one theory of disease initiation. The vulnerability of motor neurons in response to chronic peripheral nerve hyperstimulation was tested in the SOD1(G93A) rat model of ALS. A novel in vivo technique for peripheral phrenic nerve stimulation was developed via intra-diaphragm muscle electrode implantation at the phrenic motor endpoint. Chronic bilateral phrenic nerve hyperstimulation in SOD1(G93A) rats accelerated disease progression, including shortened lifespan, hastened motor neuron loss and increased denervation at diaphragm neuromuscular junctions. Hyperstimulation also resulted in focal decline in adjacent forelimb function. These results show that peripheral phrenic nerve hyperstimulation accelerates cell death of vulnerable spinal motor neurons, modifies both temporal and anatomical onset of disease, and leads to involvement of disease in adjacent anatomical regions in this ALS model.

PMID:
20381620
PMCID:
PMC2910141
DOI:
10.1016/j.nbd.2010.03.021
[Indexed for MEDLINE]
Free PMC Article
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