Degeneration of serotonin neurons triggers spasticity in amyotrophic lateral sclerosis

OBJECTIVE: is required for the development of spasticity after spinal cord injury and during amyotrophic lateral sclerosis (ALS). We sought here to provide direct evidence for a role of brainstem serotonin neurons in spasticity. METHODS: SOD1(G37R) mice expressing a conditional allele of an ALS-linked SOD1 mutation were crossed with Tph2-Cre mice expressing Cre in serotonergic neurons. Measurement of long-lasting reflex using electromyography, behavioral follow-up, and histological techniques was used to characterize spasticity and motor phenotype. RESULTS: receptors and abolished spasticity in end-stage mice. Consistent with spasticity mitigating motor symptoms, selective deletion worsened motor function and accelerated the onset of paralysis. INTERPRETATION: receptor. The wide range of drugs targeting the serotonergic system could be useful to treat spasticity in neurological diseases. Ann Neurol 2017;82:444-456.