The Onuf's nucleus and the external anal sphincter muscles in amyotrophic lateral sclerosis and Shy-Drager syndrome

Mannen, Toru; Iwata, Makoto; Toyokura, Y; Nagashima, Kazuo

doi:10.1007/bf00688606

Cited by 128 publications

(64 citation statements)

References 12 publications

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“…Second, a subset of motoneurons may die using other pathways/effectors. If the second hypothesis were true, it would be intriguing to determine whether high CRMP4 expressors correspond to particularly susceptible groups, such as the fast fatigable motoneurons innervating the lateral gastrocnemius muscle (Frey et al, 2000), and whether CRMP4 fails to be expressed in the motor nuclei (oculomotor and Onuf's nucleus) known to be ALS resistant (Mannen et al, 1982;Bergmann, 1993).…”

Section: Discussionmentioning

confidence: 99%

Collapsin Response Mediator Protein 4a (CRMP4a) Is Upregulated in Motoneurons of Mutant SOD1 Mice and Can Trigger Motoneuron Axonal Degeneration and Cell Death

Duplan¹,

Bernard²,

Casseron³

et al. 2010

J. Neurosci.

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Embryonic motoneurons from mutant SOD1 (mSOD1) mouse models of amyotrophic lateral sclerosis (ALS), but not wild-type motoneurons, can be triggered to die by exposure to nitric oxide (NO), leading to activation of a motoneuron-specific signaling pathway downstream of the death receptor Fas/CD95. To identify effectors of mSOD1-dependent cell death, we performed a proteomic analysis. Treatment of cultured mSOD1 motoneurons with NO led to a 2.5-fold increase in levels of collapsin response mediator protein 4a (CRMP4a). In vivo, the percentage of mSOD1 lumbar motoneurons expressing CRMP4 in mSOD1 mice increased progressively from presymptomatic to early-onset stages, reaching a maximum of 25%. Forced adeno-associated virus (AAV)-mediated expression of CRMP4a in wild-type motoneurons in vitro triggered a process of axonal degeneration and cell death affecting 60% of motoneurons, whereas silencing of CRMP4a in mSOD1 motoneurons protected them from NO-induced death. In vivo, AAV-mediated overexpression of CRMP4a but not CRMP2 led to the death of 30% of the lumbar motoneurons and an 18% increase in denervation of neuromuscular junctions in the gastrocnemius muscle. Our data identify CRMP4a as a potential early effector in the neurodegenerative process in ALS.

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Section: Discussionmentioning

confidence: 99%

Collapsin Response Mediator Protein 4a (CRMP4a) Is Upregulated in Motoneurons of Mutant SOD1 Mice and Can Trigger Motoneuron Axonal Degeneration and Cell Death

Duplan¹,

Bernard²,

Casseron³

et al. 2010

J. Neurosci.

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“…In fact, in amyotrophic lateral sclerosis, the motoneurons innervating the striated perineal muscles are well preserved while the ventral horn motoneurons are damaged (Mannen et al, 1978;Kiernan and Hudson, 1993). However, in the ShyDrager sindrome, whereby the SC autonomic neurons are damaged, the motoneurons innervating the striated perineal muscles are also markedly lost (Mannen et al, 1978(Mannen et al, , 1982.…”

Section: Discussionmentioning

confidence: 99%

Striated Perineal Muscles: Location of Autonomic, Sensory, and Somatic Neurons Projecting to the Male Pig Bulbospongiosus Muscle

Botti

Ragionieri

Gazza

et al. 2009

The Anatomical Record

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The location, number, and size of the neurons innervating the bulbospongiosus muscle (BSM) were studied in male pigs, by means of Fast Blue (FB) retrograde transport. After injection of FB into the left BSM, labeled neurons were found bilaterally in the L2-S4 sympathetic trunk ganglia (STGs), in the caudal mesenteric ganglia (CMGs), in the microganglia of the pelvic plexus (PGs), in a dorsolateral area with respect to the central canal of S1-S3 segments of the spinal cord (SC) and in the S1-S4 ipsilateral and S2-S3 contralateral spinal ganglia (SGs). The mean number of labeled FB cells was 3,122 AE 1,968 in STGs, 979 AE 667 in CMGs, 108 AE 104 in PGs, 89 AE 39 in SC and 77 AE 23 in SGs. The area of the multipolar neurons was 852 AE 22 lm 2 in the STGs, 878 AE 23 lm 2 in the CMGs and 922 AE 31 lm 2 in the PGs. The multipolar SC neurons had an area of 1,057 AE 38 lm 2 , while pseudounipolar SG cells had dimensions of 2,281 AE 129 lm 2 . Our research enables us to highlight two peculiarities regarding the innervation of the boar BSM: the very high number of labeled autonomic neurons and the particular localization of the motor somatic nucleus.

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“…Perineal motoneurons are relatively spared in both the human form of amyotrophic lateral sclerosis and a mouse model of the disease but are more vulnerable than other spinal motoneurons to Shy-Drager syndrome (Mannen et al, 1982;Hamson et al, 2002). Thus, in addition to furthering our understanding of neural sex differences, the mechanisms controlling the survival of perineal motoneurons are of clinical interest.…”

Section: Introductionmentioning

confidence: 99%

Effects of Bax Gene Deletion on Muscle and Motoneuron Degeneration in a Sexually Dimorphic Neuromuscular System

Jacob

Bengston²,

Forger³

2005

Journal of Neuroscience

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Motoneurons in the spinal nucleus of the bulbocavernosus (SNB) and their target muscles in the perineum, bulbocavernosus (BC), and levator ani (LA) normally degenerate in female rodents. Death of the motoneurons and muscles can be prevented by androgen treatments around the time of birth. To identify the intracellular mechanisms underlying hormone-dependent survival of this neuromuscular system, we examined mice with a targeted disruption of the pro-death gene Bax. SNB motoneuron number was increased in female Bax؊/؊ mice, whether measured using immunolabeling for a motoneuron-specific marker or retrograde labeling with the fluorescent tracer Fluoro-Gold. Based on retrograde tracing, the sex difference in SNB cell number is eliminated in Bax؊/؊ mice. Thus, Bax is required for sexually dimorphic motoneuron death in the SNB, and motoneurons rescued by Bax deletion project their axons to the periphery. Mean soma size in the SNB of Bax؊/؊ females is reduced, however, and there is a subpopulation of very small cells in the SNB of female knock-outs. In addition, the BC muscle was not identified in any female, regardless of Bax gene status. All females possessed a small LA muscle, and Bax deletion resulted in a tripling of LA fiber number in females. This increase was small, however, relative to the Ͼ50-fold sex difference in LA muscle fiber number. Thus, the sex difference in the perineal muscles is mostly unaffected by the absence of Bax protein, and SNB motoneuron number is dissociated from target muscle size in Bax؊/؊ animals.

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The Onuf's nucleus and the external anal sphincter muscles in amyotrophic lateral sclerosis and Shy-Drager syndrome

Cited by 128 publications

References 12 publications

Collapsin Response Mediator Protein 4a (CRMP4a) Is Upregulated in Motoneurons of Mutant SOD1 Mice and Can Trigger Motoneuron Axonal Degeneration and Cell Death

Collapsin Response Mediator Protein 4a (CRMP4a) Is Upregulated in Motoneurons of Mutant SOD1 Mice and Can Trigger Motoneuron Axonal Degeneration and Cell Death

Striated Perineal Muscles: Location of Autonomic, Sensory, and Somatic Neurons Projecting to the Male Pig Bulbospongiosus Muscle

Effects of Bax Gene Deletion on Muscle and Motoneuron Degeneration in a Sexually Dimorphic Neuromuscular System

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