The serotonin precursor 5-hydroxytryptophan delays neuromuscular disease in murine familial amyotrophic lateral sclerosis.
BACKGROUND
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.
Turner
B J
BJ
Neurodegeneration Research Laboratory, Department of Anatomy and Cell Biology, Monash University, Victoria, Australia.
Lopes
E C
EC
Cheema
S S
SS
D006916:5-Hydroxytryptophan / Q000008:administration & dosage / Q000627:therapeutic use*; D000375:Aging; D000409:Alanine / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005998:Glycine / Q000235:genetics; D006614:Hindlimb; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009026:Mortality; D009043:Motor Activity / Q000187:drug effects; D009154:Mutation; D010243:Paralysis / Q000209:etiology / Q000517:prevention & control; D012701:Serotonin / Q000097:blood; D013482:Superoxide Dismutase / Q000235:genetics
D012701:Serotonin; D006916:5-Hydroxytryptophan; D013482:Superoxide Dismutase; D000409:Alanine; D005998:Glycine