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

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.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Lepore AC,Tolmie C,O'Donnell J,Wright MC,Dejea C,Rauck B,Hoke A,Ignagni AR,Onders RP,Maragakis NJ

doi

10.1016/j.nbd.2010.03.021

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

252-64

issue

3

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(10)00093-8

journal_volume

39

pub_type

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