Chronic stress impacts energy metabolism and triggers motor neuropathy in an Optineurin knockout mouse model

Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset progressive motor neurodegenerative disease. To study whether in vivo loss of the multifunctional adaptor protein Optineurin (OPTN) triggers ALS, a whole-body optineurin knock-out (Optn KO) mice was generated. In the absence of a clinical phenotype, we investigated the role of chronic stress as a potential ‘determinant’ of motor phenotype in Optn deficient background. Progressive motor impairment was observed after 30 days from chronic variable mild stress (CVMS) exposure in KO stressed mice. This occurs as a result of neurodegeneration and reactive gliosis associated with neuronal glucose hypometabolism and astroglial hypermetabolism.