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

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• 作者：Angelo C. Lepore ; Christopher Tolmie ; John O'Donnell ; Megan C. Wright ; Christine Dejea ; Britta Rauck ; Ahmet Hoke ; Anthony R. Ignagni ; Raymond P. Onders ; Nicholas J. Maragakis
• 关键词：Motor neuron ; Neurodegeneration ; ALS ; Amyotrophic lateral sclerosis ; SOD1 ; Phrenic nerve ; Diaphragm ; Diaphragm pacing ; Diaphragm stimulation ; Respiratory ; Disease onset ; Environment
• 刊名：Neurobiology of Disease
• 出版年：2010
• 出版时间：September 2010
• 年：2010
• 卷：39
• 期：3
• 页码：252-264
• 全文大小：1981 K

文摘

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.