Essential fatty acids given from conception prevent topographies of motor deficit in a transgenic model of Huntington's disease.
Transgenic R6/1 mice incorporate a human genomic fragment containing promoter elements exon 1 and a portion of intron 2 of the Huntingtin gene responsible for Huntington's disease. They develop late-onset neurological deficits in a manner similar to the motor abnormalities of the disorder. As essential fatty acids are phospholipid components of cell membranes which may influence cell death and movement disorder phenotype, R6/1 and normal mice were randomised to receive a mixture of essential fatty acids or placebo on alternate days throughout life. Over mid-adulthood, topographical assessment of behaviour revealed R6/1 transgenics to evidence progressive shortening of stride length, with progressive reductions in locomotion, elements of rearing, sniffing, sifting and chewing, and an increase in grooming. These deficits were either not evident or materially diminished in R6/1 transgenics receiving essential fatty acids. R6/1 transgenics also showed reductions in body weight and in brain dopamine D(1)-like and D(2)-like quantitative receptor autoradiography which were unaltered by essential fatty acids.These findings indicate that early and sustained treatment with essential fatty acids are able to protect against motor deficits in R6/1 transgenic mice expressing exon 1 and a portion of intron 2 of the Huntingtin gene, and suggest that essential fatty acids may have therapeutic potential in Huntington's disease.
Clifford
J J
JJ
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland. jclifford@rcsi.ie
Drago
J
J
Natoli
A L
AL
Wong
J Y F
JY
Kinsella
A
A
Waddington
J L
JL
Vaddadi
K S
KS
D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005228:Fatty Acids, Essential / Q000494:pharmacology*; D005260:Female; D005526:Food, Formulated; D006816:Huntington Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D005228:Fatty Acids, Essential; D018696:Neuroprotective Agents