%0 Journal Article
%T Improvement of neuropathology and transcriptional deficits in CAG 140 knock-in mice supports a beneficial effect of dietary curcumin in Huntington's disease
%A Miriam A Hickey
%A Chunni Zhu
%A Vera Medvedeva
%A Renata P Lerner
%A Stefano Patassini
%A Nicholas R Franich
%A Panchanan Maiti
%A Sally A Frautschy
%A Scott Zeitlin
%A Michael S Levine
%A Marie-Fran£żoise Chesselet
%J Molecular Neurodegeneration
%D 2012
%I BioMed Central
%R 10.1186/1750-1326-7-12
%X KI mice fed a curcumin-containing diet since conception showed decreased huntingtin aggregates and increased striatal DARPP-32 and D1 receptor mRNAs, as well as an amelioration of rearing deficits. However, similar to other antioxidants, curcumin impaired rotarod behavior in both WT and KI mice and climbing in WT mice. These behavioral effects were also noted in WT C57Bl/6 J mice exposed to the same curcumin regime as adults. However, neither locomotor function, behavioral despair, muscle strength or food utilization were affected by curcumin in this latter study. The clinical significance of curcumin's impairment of motor performance in mice remains unclear because curcumin has an excellent blood chemistry and adverse event safety profile, even in the elderly and in patients with Alzheimer's disease.Together with this clinical experience, the improvement in several transgene-dependent parameters by curcumin in our study supports a net beneficial effect of dietary curcumin in HD.Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an elongated, unstable, polyglutamine repeat near the N terminus of the huntingtin gene [1]. Recent studies have shown that many symptoms including behavioral, cognitive and motor changes are present in gene carriers decades prior to the clinical onset of the disease [2,3]. Further, pathological changes including striatal atrophy, cortical thinning and white matter loss, aggregates of mutant huntingtin, receptor loss and microgliosis are present many years prior to predicted age of disease onset [4-10]. Therefore neuroprotective treatments may need to be started in gene carriers long before the onset of manifest disease [7]. This requires the use of drugs with an excellent safety profile over long periods of administration. Moreover, it is possible that this early drug treatment could prevent later downstream toxicity due to the huntingtin protein.CAG140 knock-in (KI) mice are a slowly progressing mouse m
%K Huntingtin aggregates
%K Open field
%K Climbing
%K Pole task
%K Rotarod
%K Grip strength
%K Striatal mRNA transcripts
%K Preclinical therapeutic trial
%U http://www.molecularneurodegeneration.com/content/7/1/12