Peripheral hyperstimulation alters site of disease onset and course in SOD1 rats.
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.
Lepore
Angelo C
AC
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tolmie
Christopher
C
O'Donnell
John
J
Wright
Megan C
MC
Dejea
Christine
C
Rauck
Britta
B
Hoke
Ahmet
A
Ignagni
Anthony R
AR
Onders
Raymond P
RP
Maragakis
Nicholas J
NJ
D000200:Action Potentials / Q000502:physiology*; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004576:Electromyography; D005260:Female; D018737:Hand Strength / Q000502:physiology*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010791:Phrenic Nerve / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D055647:Rats, Transgenic; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
Brain. 1997 Oct;120 ( Pt 10):1723-37
9365366
Neurology. 2003 Sep 23;61(6):742-9
14504315
Neuroreport. 2002 Jun 12;13(8):1067-70
12060810
Ann Neurol. 1997 Feb;41(2):210-21
9029070
J Neurosci Res. 2006 Jan;83(1):119-33
16342121
J Neurosci. 2001 Dec 1;21(23):9246-54
11717358
Neuromolecular Med. 2008;10(2):108-17
18286388
Phys Med Rehabil Clin N Am. 2008 Aug;19(3):461-77, viii
18625410
Phys Med Rehabil Clin N Am. 2008 Aug;19(3):545-57, ix-x
18625415
Eur J Neurosci. 2004 Dec;20(11):3115-20
15579165
J Neurol Sci. 2007 Nov 15;262(1-2):45-53
17681549
Neurobiol Dis. 2002 Aug;10(3):268-78
12270689
Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1604-9
11818550
Science. 1994 Jun 17;264(5166):1772-5
8209258
J Neurol Neurosurg Psychiatry. 2001 Aug;71(2):265-7
11459909
Nature. 1993 Mar 4;362(6415):59-62
8446170
Brain. 1995 Jun;118 ( Pt 3):707-19
7600088
Glia. 2005 Sep;51(4):241-53
15846792
Ageing Res Rev. 2004 Jan;3(1):105-20
15163105
Neurosci Lett. 2007 May 1;417(2):206-11
17412505
J Comp Neurol. 2007 Sep 1;504(1):1-16
17614103
Adv Neurol. 1991;56:245-70
1853761
Muscle Nerve. 2004 May;29(5):656-62
15116368
Exp Neurol. 2004 Feb;185(2):232-40
14736504
Nature. 2002 May 2;417(6884):74-8
11986668
J Neurobiol. 2003 Mar;54(4):566-76
12555269
Science. 2006 Jun 2;312(5778):1389-92
16741123
J Surg Res. 1981 Feb;30(2):142-53
7464109
Neuroscience. 2002;115(2):331-5
12421599
J Comp Neurol. 1999 Sep 20;412(2):373-80
10441762
PLoS One. 2009 Oct 06;4(10):e7357
19806196
Amyotroph Lateral Scler. 2009 Oct-Dec;10(5-6):295-301
19922116
Neurology. 2003 Sep 23;61(6):750-6
14504316
Neurobiol Dis. 2006 Jan;21(1):110-8
16084734
Neuron. 1995 Jun;14(6):1105-16
7605627
Nat Neurosci. 2008 Nov;11(11):1294-301
18931666
J Neurosci Res. 2005 Oct 1;82(1):63-70
16108072
Amyotroph Lateral Scler. 2009 Oct-Dec;10(5-6):302-9
19922117
Neurology. 2006 Sep 12;67(5):761-5
16899545
Nat Neurosci. 2008 Mar;11(3):251-3
18246065
Neuromuscul Disord. 2003 Nov;13(9):737-43
14561497
Neuroscience. 2005;130(4):897-910
15652988
Neuron. 1997 Feb;18(2):327-38
9052802
Ann Neurol. 2003 Jun;53(6):804-7
12783429