Source
Neurodegeneration Research Laboratory, Department of Anatomy and Cell Biology, Monash University, Victoria, Australia.
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.