title: Soma size and Cav1.3 channel expression in vulnerable and resistant motoneuron populations of the SOD1G93A mouse model of ALS.
abstract: Although the loss of motoneurons is an undisputed feature of amyotrophic lateral sclerosis (ALS) in man and in its animal models (SOD1 mutant mice), how the disease affects the size and excitability of motoneurons prior to their degeneration is not well understood. This study was designed to test the hypothesis that motoneurons in mutant SOD1(G93A) mice exhibit an enlargement of soma size (i.e., cross-sectional area) and an increase in Cav1.3 channel expression at postnatal day 30, well before the manifestation of physiological symptoms that typically occur at p90 (Chiu et al. 1995). We made measurements of spinal and hypoglossal motoneurons vulnerable to degeneration, as well as motoneurons in the oculomotor nucleus that are resistant to degeneration. Overall, we found that the somata of motoneurons in male SOD1(G93A) mutants were larger than those in wild-type transgenic males. When females were included in the two groups, significance was lost. Expression levels of the Cav1.3 channels were not differentiated by genotype, sex, or any interaction of the two. These results raise the intriguing possibility of an interaction between male sex steroid hormones and the SOD1 mutation in the etiopathogenesis of ALS.
authors.affiliation: Graduate Program in Neurobiology & Behavior, University of Washington, Seattle, Washington, USA.
authors.forename: Liza
authors.initials: L
authors.lastname: Shoenfeld
authors.affiliation: Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Westenbroek
authors.affiliation: Department of Physiology & Biophysics, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Fisher
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Katharina A
authors.initials: KA
authors.lastname: Quinlan
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA Department of Physical Therapy and Human Movement Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Vicki M
authors.initials: VM
authors.lastname: Tysseling
authors.affiliation: Department of Physiology & Biophysics, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Randall K
authors.initials: RK
authors.lastname: Powers
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA Department of Physical Therapy and Human Movement Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Heckman
authors.affiliation: Graduate Program in Neurobiology & Behavior, University of Washington, Seattle, Washington, USA Department of Physiology & Biophysics, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Binder
keywords: ALS; Cav1.3 channels; motoneuron size; motoneurons in SOD1G93A mice
references.citation: Muscle Nerve. 2009 Mar;39(3):318-27
references.pmid: 19208415
references.citation: Tissue Eng Part C Methods. 2012 Aug;18(8):583-92
references.pmid: 22320435
references.citation: Neuron. 2013 Aug 7;79(3):416-38
references.pmid: 23931993
references.citation: J Endocrinol. 1980 Oct;87(1):81-7
references.pmid: 7430918
references.citation: J Comp Neurol. 2000 Jan 3;416(1):112-25
references.pmid: 10578106
references.citation: Exp Neurol. 2013 Sep;247:91-100
references.pmid: 23578819
references.citation: J Neurophysiol. 2004 Jan;91(1):571-5
references.pmid: 14523070
references.citation: Trends Neurosci. 1988 Oct;11(10):465-9
references.pmid: 2469166
references.citation: Neurosci Lett. 2002 Dec 19;335(1):39-43
references.pmid: 12457737
references.citation: Biochim Biophys Acta. 2000 Jan 10;1495(1):51-68
references.pmid: 10634932
references.citation: J Cell Biol. 1993 Nov;123(4):949-62
references.pmid: 8227151
references.citation: Gend Med. 2010 Dec;7(6):557-70
references.pmid: 21195356
references.citation: J Biol Chem. 2011 Dec 9;286(49):42736-42748
references.pmid: 21998310
references.citation: J Neurosci. 2008 Oct 22;28(43):10864-74
references.pmid: 18945894
references.citation: Eur J Neurosci. 2000 May;12(5):1635-46
references.pmid: 10792441
references.citation: J Neurochem. 2004 Jan;88(2):481-93
references.pmid: 14690536
references.citation: Science. 1994 Jun 17;264(5166):1772-5
references.pmid: 8209258
references.citation: Nature. 1993 Mar 4;362(6415):59-62
references.pmid: 8446170
references.citation: Mol Cell Neurosci. 1995 Aug;6(4):349-62
references.pmid: 8846004
references.citation: Neuroscience. 2009 Mar 3;159(1):217-35
references.pmid: 19136044
references.citation: J Physiol. 2011 May 1;589(Pt 9):2245-60
references.pmid: 21486770
references.citation: Eur J Neurosci. 2007 Jan;25(2):451-9
references.pmid: 17284186
references.citation: Neurobiol Dis. 2007 Nov;28(2):154-64
references.pmid: 17766128
references.citation: J Neurosci. 2001 Aug 15;21(16):5944-51
references.pmid: 11487617
references.citation: Ann Neurol. 2009 Jan;65 Suppl 1:S3-9
references.pmid: 19191304
references.citation: J Physiol. 2000 Jun 1;525 Pt 2:433-45
references.pmid: 10835045
references.citation: J Neurosci. 2000 Apr 1;20(7):2534-42
references.pmid: 10729333
references.citation: J Neurosci. 2010 Apr 21;30(16):5544-58
references.pmid: 20410108
references.citation: Nat Neurosci. 2006 Mar;9(3):408-19
references.pmid: 16474388
references.citation: Brain. 1991 Apr;114 ( Pt 2):843-53
references.pmid: 2043953
references.citation: J Neurochem. 1998 Mar;70(3):1054-60
references.pmid: 9489725
references.citation: J Neurophysiol. 1996 Sep;76(3):2107-10
references.pmid: 8890322
references.citation: Integr Comp Biol. 2011 Dec;51(6):913-25
references.pmid: 21989221
references.citation: Brain. 1993 Feb;116 ( Pt 1):203-15
references.pmid: 8453457
references.citation: Ann N Y Acad Sci. 1994 Nov 14;743:141-61; discussion 161-4
references.pmid: 7802411
references.citation: J Neurosci. 1998 Aug 15;18(16):6319-30
references.pmid: 9698323
references.citation: Eur J Neurosci. 1999 Oct;11(10):3481-7
references.pmid: 10564356
references.citation: J Comp Neurol. 2008 Nov 20;511(3):329-41
references.pmid: 18803237
references.citation: Neuron. 1991 Jul;7(1):35-44
references.pmid: 1648940
references.citation: J Neurol Neurosurg Psychiatry. 2011 Jun;82(6):635-7
references.pmid: 21551173
references.citation: J Musculoskelet Neuronal Interact. 2010 Jun;10(2):180-7
references.pmid: 20516636
references.citation: Prog Mol Biol Transl Sci. 2012;107:215-62
references.pmid: 22482452
references.citation: Amyotroph Lateral Scler. 2007 Feb;8(1):20-5
references.pmid: 17364431
references.citation: Rev Physiol Biochem Pharmacol. 2001;143:137-263
references.pmid: 11428264
references.citation: Neuromuscul Disord. 2003 Nov;13(9):737-43
references.pmid: 14561497