A conditioning lesion provides selective protection in a rat model of Amyotrophic Lateral Sclerosis

Autor: Thais Federici, Brooke R. Snyder, Bethwel Raore, Michele A. Kliem, Christina Krudy, Nicholas M. Boulis, Eric T. Quach, Colin K. Franz
Rok vydání: 2009
Předmět:
Pathology
Neurological Disorders/Peripheral Neuropathies
medicine.medical_treatment
lcsh:Medicine
Neuroscience/Motor Systems
Trauma
Nervous System
Amyotrophic lateral sclerosis
lcsh:Science
Tibial nerve
Neurological Disorders/Spinal Disorders
Neurological Disorders/Movement Disorders
Motor Neurons
Multidisciplinary
musculoskeletal
neural
and ocular physiology
Cell Biology/Cellular Death and Stress Responses
musculoskeletal system
medicine.anatomical_structure
Neurological Disorders/Neurorehabilitation and Trauma
Crush injury
medicine.symptom
Axotomy
Rats
Transgenic
Neuroscience/Neurobiology of Disease and Regeneration
Research Article
medicine.medical_specialty
Cell Survival
Neuromuscular Junction
Neurological Disorders/Neuromuscular Diseases
Neurological Disorders
Neuromuscular junction
Lesion
Atrophy
medicine
Animals
Muscle Strength
Spinal Cord Injuries
Cryopreservation
business.industry
Superoxide Dismutase
Surgery/Neurosurgery
lcsh:R
Amyotrophic Lateral Sclerosis
Muscle weakness
medicine.disease
Axons
Rats
Disease Models
Animal
nervous system
Cell Biology/Neuronal and Glial Cell Biology
lcsh:Q
business
Neuroscience
Zdroj: PLoS ONE
PLoS ONE, Vol 4, Iss 10, p e7357 (2009)
ISSN: 1932-6203
Popis: Background: Amyotrophic Lateral Sclerosis (ALS) is neurodegenerative disease characterized by muscle weakness and atrophy due to progressive motoneuron loss. The death of motoneuron is preceded by the failure of neuromuscular junctions (NMJs) and axonal retraction. Thus, to develop an effective ALS therapy you must simultaneously preserve motoneuron somas, motor axons and NMJs. A conditioning lesion has the potential to accomplish this since it has been shown to enhance neuronal survival and recovery from trauma in a variety of contexts. Methodology/Principal Findings: To test the effects of a conditioning lesion in a model of familial ALS we administered a tibial nerve crush injury to presymptomatic fALS G93A rats. We examined its effects on motor function, motoneuron somas, motor axons, and NMJs. Our experiments revealed a novel paradigm for the conditioning lesion effect. Specifically we found that the motor functional decline in fALS G93A rats that received a conditioning lesion was delayed and less severe. These improvements in motor function corresponded to greater motoneuron survival, reduced motor axonopathy, and enhanced NMJ maintenance at disease end-stage. Furthermore, the increased NMJ maintenance was selective for muscle compartments innervated by the most resilient (slow) motoneuron subtypes, but was absent in muscle compartments innervated by the most vulnerable (fast fatigable) motoneuron subtypes. Conclusions/Significance: These findings support the development of strategies aimed at mimicking the conditioning lesion effect to treat ALS as well as underlined the importance of considering the heterogeneity of motoneuron sub-types when evaluating prospective ALS therapeutics.
Databáze: OpenAIRE
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