Abstract
Transgenic mice expressing the human superoxide dismutase 1 (SOD-1) mutant at position 93 (G93A) develop a phenotype resembling amyotrophic lateral sclerosis (ALS). In fact, G93A mice develop progressive motor deficits which finally lead to motor palsy and death. This is due to the progressive degeneration of motor neurons in the ventral horn of the spinal cord. Although a similar loss is reported for specific cranial motor nuclei, only a few studies so far investigated degeneration in a few brainstem nuclei. We recently reported that chronic lithium administration delays onset and duration of the disease, while reducing degeneration of spinal motor neuron. In the present study, we extended this investigation to all somatic motor nuclei of the brain stem in the G93A mice and we evaluated whether analogous protective effects induced by lithium in the spinal cord were present at the brain stem level. We found that all motor but the oculomotor nuclei were markedly degenerated in G93A mice, and chronic treatment with lithium significantly attenuated neurodegeneration in the trigeminal, facial, ambiguus, and hypoglossal nuclei. Moreover, in the hypoglossal nucleus, we found that recurrent collaterals were markedly lost in G93A mice while they were rescued by chronic lithium administration.
MeSH terms
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Amyotrophic Lateral Sclerosis / drug therapy*
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Amyotrophic Lateral Sclerosis / pathology
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Amyotrophic Lateral Sclerosis / physiopathology
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Animals
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Axons / drug effects
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Axons / pathology
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Biomarkers / analysis
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Biomarkers / metabolism
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Brain Mapping / methods
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Brain Stem / drug effects*
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Brain Stem / pathology
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Brain Stem / physiopathology
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Choline O-Acetyltransferase / analysis
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Choline O-Acetyltransferase / metabolism
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Cranial Nerves / drug effects*
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Cranial Nerves / pathology
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Cranial Nerves / physiopathology
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Cytoprotection / drug effects
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Cytoprotection / physiology
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Disease Models, Animal
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Drug Administration Schedule
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Facial Nerve / drug effects
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Facial Nerve / pathology
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Facial Nerve / physiopathology
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Humans
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Hypoglossal Nerve / drug effects
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Hypoglossal Nerve / pathology
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Hypoglossal Nerve / physiopathology
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Lithium / pharmacology*
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Lithium / therapeutic use
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Male
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Mice
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Mice, Transgenic
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Motor Neurons / metabolism*
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Motor Neurons / pathology
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Nerve Degeneration / drug therapy
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Nerve Degeneration / physiopathology
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Nerve Degeneration / prevention & control
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Neuroprotective Agents / pharmacology*
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Neuroprotective Agents / therapeutic use
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Treatment Outcome
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Trigeminal Nerve / drug effects
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Trigeminal Nerve / pathology
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Trigeminal Nerve / physiopathology
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Vagus Nerve / drug effects
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Vagus Nerve / pathology
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Vagus Nerve / physiopathology
Substances
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Biomarkers
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Neuroprotective Agents
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Lithium
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Choline O-Acetyltransferase