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

NEUROBIOLOGY OF DISEASE

卷:39

Article

Lepore, Angelo C.¹  Tolmie, Christopher¹  O'Donnell, John¹  Wright, Megan C.¹  Dejea, Christine¹  Rauck, Britta¹  Hoke, Ahmet¹  Ignagni, Anthony R.²  Onders, Raymond P.^3,4  Maragakis, Nicholas J.¹ 

[1] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21218 USA

[2] Synapse Biomed Inc, Cleveland, OH USA

[3] Univ Hosp, Dept Surg, Case Med Ctr, Cleveland, OH USA

[4] Case Western Reserve Univ, Cleveland, OH 44106 USA

关键词: Motor neuron;    Neurodegeneration;    ALS;    Amyotrophic lateral sclerosis;    SOD1;    Phrenic nerve;    Diaphragm;    Diaphragm pacing;    Diaphragm stimulation;    Respiratory;    Disease onset;    Environment;   

DOI  :  10.1016/j.nbd.2010.03.021

来源: Elsevier

【 摘 要 】

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. Published by Elsevier Inc.

【 授权许可】

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