The immunophilin ligand FK506, but not the P38 kinase inhibitor SB203580, improves function of adult rat muscle reinnervated from transplants of embryonic neurons

Grumbles, Robert M.; Casella, Gizelda; Rudinsky, Michelle J.; Godfrey, Sharlene; Wood, Patrick M.; Thomas, Christine K.

doi:10.1016/j.neuroscience.2004.09.024

Cited by 17 publications

(28 citation statements)

References 50 publications

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“…Animals implanted with ES-cell-derived MNs demonstrated significant attenuation of muscle atrophy when compared with surgical control muscles after 3 months of denervation. A similar reduction in whole muscle atrophy has been reported after transplantation of embryonic MNs into the rat tibial nerve (Thomas et al, 2000(Thomas et al, , 2003Grumbles et al, 2005Grumbles et al, , 2007.…”

Section: Discussionsupporting

confidence: 78%

Transplanted Mouse Embryonic Stem-Cell-Derived Motoneurons Form Functional Motor Units and Reduce Muscle Atrophy

Yohn¹,

Miles²,

Rafuse³

et al. 2008

J. Neurosci.

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Prolonged muscle denervation resulting from motor neuron (MN) damage leads to atrophy and degeneration of neuromuscular junctions (NMJs), which can impart irreversible damage. In this study, we ask whether transplanted embryonic stem (ES) cells differentiated into MNs can form functional synapses with host muscle, and if so what effects do they have on the muscle. After transplantation into transected tibial nerves of adult mice, ES-cell-derived MNs formed functional synapses with denervated host muscle, which resulted in the ability to produce average tetanic forces of 44% of nonlesioned controls. ES-cell-derived motor units (MUs) had mean force values and ranges similar to control muscles. The number of type I fibers and fatigue resistance of the MUs were increased, and denervationassociated muscle atrophy was significantly reduced. These results demonstrate the capacity for ES-cell-derived MNs not only to incorporate into the adult host tissue, but also to exert changes in the target tissue. By providing the signals normally active during embryonic development and placing the cells in an environment with their target tissue, ES cells differentiate into MNs that give rise to functional MU output which resembles the MU output of endogenous MNs. This suggests that these signals combined with those present in the graft environment, lead to the activation of a program intended to produce a normal range of MU forces.

show abstract

Section: Discussionsupporting

confidence: 78%

Transplanted Mouse Embryonic Stem-Cell-Derived Motoneurons Form Functional Motor Units and Reduce Muscle Atrophy

Yohn¹,

Miles²,

Rafuse³

et al. 2008

J. Neurosci.

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show abstract

“…This is the case when neurons are implanted into a peripheral nerve or the central nervous system. [35][36][37][38][39][40] In support of this idea, motoneuron survival, muscle reinnervation, and motor unit function are all promoted when a combination of neurotrophic factors is included with the transplanted neurons. 41,42 Neuron survival is also activity dependent, 43 and developing neurons are excitable.…”

Section: Introductionmentioning

confidence: 91%

Acute Stimulation of Transplanted Neurons Improves Motoneuron Survival, Axon Growth, and Muscle Reinnervation

Grumbles

Liu

Thomas

et al. 2013

Journal of Neurotrauma

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Few options exist for treatment of pervasive motoneuron death after spinal cord injury or in neurodegenerative diseases such as amyotrophic lateral sclerosis. Local transplantation of embryonic motoneurons into an axotomized peripheral nerve is a promising approach to arrest the atrophy of denervated muscles; however, muscle reinnervation is limited by poor motoneuron survival. The aim of the present study was to test whether acute electrical stimulation of transplanted embryonic neurons promotes motoneuron survival, axon growth, and muscle reinnervation. The sciatic nerve of adult Fischer rats was transected to mimic the widespread denervation seen after disease or injury. Acutely dissociated rat embryonic ventral spinal cord cells were transplanted into the distal tibial nerve stump as a neuron source for muscle reinnervation. Immediately post-transplantation, the cells were stimulated at 20 Hz for 1 h. Other groups were used to control for the cell transplantation and stimulation. When neurons were stimulated acutely, there were significantly more neurons, including cholinergic neurons, 10 weeks after transplantation. This led to enhanced numbers of myelinated axons, reinnervation of more muscle fibers, and more medial and lateral gastrocnemius muscles were functionally connected to the transplant. Reinnervation reduced muscle atrophy significantly. These data support the concept that electrical stimulation rescues transplanted motoneurons and facilitates muscle reinnervation.

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“…; Loberg et al, 2007) or SB203580 (2.5 mg/kg/day, i.p. ; Grumbles et al, 2005) were administered to the animals for 1 h prior to the start of the acute PTE protocol. In the acute PTE +resveratrol +SB203580 group, we pre-treated rats with SB203580 (2.5 mg/kg/day, i.p.)…”

Section: Animals and Experimental Groupsmentioning

confidence: 99%

Resveratrol downregulates acute pulmonary thromboembolism-induced pulmonary artery hypertension via p38 mitogen-activated protein kinase and monocyte chemoattractant protein-1 signaling in rats

et al. 2012

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The immunophilin ligand FK506, but not the P38 kinase inhibitor SB203580, improves function of adult rat muscle reinnervated from transplants of embryonic neurons

Cited by 17 publications

References 50 publications

Transplanted Mouse Embryonic Stem-Cell-Derived Motoneurons Form Functional Motor Units and Reduce Muscle Atrophy

Transplanted Mouse Embryonic Stem-Cell-Derived Motoneurons Form Functional Motor Units and Reduce Muscle Atrophy

Acute Stimulation of Transplanted Neurons Improves Motoneuron Survival, Axon Growth, and Muscle Reinnervation

Resveratrol downregulates acute pulmonary thromboembolism-induced pulmonary artery hypertension via p38 mitogen-activated protein kinase and monocyte chemoattractant protein-1 signaling in rats

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