title: Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington's disease mice.
abstract: Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD(140Q/140Q)). Primary HD(140Q/140Q) cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD(140Q/140Q) neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD(140Q/140Q) neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD.
authors.affiliation: Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. xli12@partners.org
authors.forename: Xueyi
authors.initials: X
authors.lastname: Li
authors.forename: Antonio
authors.initials: A
authors.lastname: Valencia
authors.forename: Hollis
authors.initials: H
authors.lastname: McClory
authors.forename: Ellen
authors.initials: E
authors.lastname: Sapp
authors.forename: Kimberly B
authors.initials: KB
authors.lastname: Kegel
authors.forename: Marian
authors.initials: M
authors.lastname: Difiglia
mesh_terms: D000818:Animals; D055879:Gene Knock-In Techniques; D005947:Glucose / Q000378:metabolism*; D006816:Huntington Disease / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009474:Neurons / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D005947:Glucose; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins