Chronic lithium chloride treatment has variable effects on motor behaviour and survival of mice transgenic for the Huntington's disease mutation.
Expression of the Huntington's disease (HD) mutation in mice (R6/2 line) causes a progressive neurological phenotype that includes deterioration of motor function resembling that seen in HD. The current study sought to determine whether or not chronic treatment of R6/2 mice with lithium chloride would have an effect on the progression of the phenotype, in light of lithium's reported neuroprotective and anti-depressive properties. Treatment began either before or after the onset of symptoms. Chronic treatment with lithium caused a significant improvement in rotarod performance when treatment was started post- but not pre-symptomatically. There was no overall effect on survival in either group, but further analysis revealed that in the post-symptomatic group, mice could be assigned to one of two distinct groups, depending on the effects of lithium. One subgroup of mice lost weight faster, died earlier and showed rotarod performance similar to the vehicle-treated controls. The other subgroup lost weight at a normal rate, died at a similar age, but showed greatly improved motor performance compared to controls. The improvement in rotarod performance suggests that lithium may improve motor symptoms as well as depression in some HD patients.
Wood
Nigel I
NI
Department of Pharmacology, University of Cambridge, Tennis Court Road, CB2 1PD Cambridge, UK. niw20@cam.ac.uk
Morton
A Jennifer
AJ
D000375:Aging / Q000187:drug effects; D000818:Animals; D018692:Antimanic Agents / Q000627:therapeutic use*; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004333:Drug Administration Routes / Q000662:veterinary; D005260:Female; D006816:Huntington Disease / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D018021:Lithium Chloride / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects*; D009154:Mutation; D009636:Norbornanes; D010641:Phenotype; D011597:Psychomotor Performance / Q000187:drug effects; D012399:Rotation; D013534:Survival; D013997:Time Factors
D018692:Antimanic Agents; D009636:Norbornanes; D018021:Lithium Chloride; C020900:fencamfamine