Mutant SOD1 prevents normal functional recovery through enhanced glial activation and loss of motor neuron innervation after peripheral nerve injury.

This study identified a relationship between genetic and environmental contributions to disease onset and progression in ALS. The findings suggest that injury induced SOD1 mutant protein induces a heightened and prolonged inflammatory response resulting in motor neuron degeneration through synaptic loss. Once initiated, this process spreads to adjacent motor neurons leading to contiguous spread of the disease. Treatments that suppress this heightened glial response could slow disease progression in ALS patients with focal sites of disease onset. SIGNIFICANCE STATEMENT: The contribution of environmental factors such as peripheral nerve insults in ALS is not well understood. Here we examined the effect of a single sciatic nerve injury in SOD1 (G93A) rats to explore the contribution of this environmental insult on disease onset and progression. After the injury, SOD1 animals failed to recover and had a more rapid functional decline. Histopathologically, SOD1 animals had heightened SOD1 expression, microglial and astroglial responses, and a reduction of motor neuron innervation. Taken together, these results provide a plausible mechanism of how the SOD1 mutated protein promotes an abnormal response to injury that leads to neurodegenerative changes in an ALS model that is amenable to therapeutic testing. PMID: 30594811 [PubMed - as supplied by publisher]
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research