The serotonin precursor 5‐hydroxytryptophan delays neuromuscular disease in murine familial amyotrophic lateral sclerosis

Abstract

INTRODUCTION: Reduction in the levels of whole‐blood serotonin is a common feature of Down syndrome (DS) individuals and transgenic mice overexpressing wild‐type SOD1. Administration of the metabolic precursor 5‐hydroxytryptophan (5‐HTP) leads to reversal of both serotonin deficits and hypotonia in humans. The effect of 5‐HTP treatment on the progression of motor neuron disease in mutant SOD1 mice was examined.

METHODS: Pre‐disease transgenic SOD1 G93A mice and wild‐type littermates were systemically administered 5‐HTP thrice weekly (0, 5 or 50 mg/kg). Animal weights, locomotor function and survival were recorded weekly. Plasma serotonin levels were measured post‐mortem.

RESULTS: Treatment with 5‐HTP significantly delayed hindlimb weakness and mortality in SOD1 G93A mice in a dose‐dependent manner. Wild‐type mice were not adversely affected by 5‐HTP administration. Baseline serotonin levels did not differ between wild‐type and ALS mice. Blood platelet serotonin levels increased proportionally with dose.

CONCLUSIONS: Increased blood serotonin by administration of 5‐HTP in SOD1 G93A mice led to improved locomotor function and survival. A role for serotonin metabolism in mice with elevated SOD1 expression and motor neuron disease is suggested by these studies.

• Down syndrome
• motor neuron disease
• serotonin
• SOD1 G93A transgenic mouse
• superoxide dismutase 1