title: Mice with selective elimination of striatal acetylcholine release are lean, show altered energy homeostasis and changed sleep/wake cycle.
abstract: Cholinergic neurons are known to regulate striatal circuits; however, striatal-dependent physiological outcomes influenced by acetylcholine (ACh) are still poorly under;?>stood. Here, we used vesicular acetylcholine transporter (VAChT)(D2-Cre-flox/flox)  mice, in which we selectively ablated the vesicular acetylcholine transporter in the striatum to dissect the specific roles of striatal ACh in metabolic homeostasis. We report that VAChT(D)             (2-Cre-flox/flox)  mice are lean at a young age and maintain this lean phenotype with time. The reduced body weight observed in these mutant mice is not attributable to reduced food intake or to a decrease in growth rate. In addition, changed activity could not completely explain the lean phenotype, as only young VAChT(D)             (2-Cre-flox/flox)  mice showed increased physical activity. Interestingly, VAChT(D)             (2-Cre-flox/flox)  mice show several metabolic changes, including increased plasma levels of insulin and leptin. They also show increased periods of wakefulness when compared with littermate controls. Taken together, our data suggest that striatal ACh has an important role in the modulation of metabolism and highlight the importance of striatum cholinergic tone in the regulation of energy expenditure. These new insights on how cholinergic neurons influence homeostasis open new avenues for the search of drug targets to treat obesity.
authors.affiliation: Robarts Research Institute, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Monica S
authors.initials: MS
authors.lastname: Guzman
authors.forename: Xavier
authors.initials: X
authors.lastname: De Jaeger
authors.forename: Maria
authors.initials: M
authors.lastname: Drangova
authors.forename: Marco A M
authors.initials: MA
authors.lastname: Prado
authors.forename: Robert
authors.initials: R
authors.lastname: Gros
authors.forename: Vania F
authors.initials: VF
authors.lastname: Prado
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D012890:Sleep / Q000502:physiology*; D050494:Vesicular Acetylcholine Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C493460:Slc18a3 protein, mouse; D050494:Vesicular Acetylcholine Transport Proteins; D000109:Acetylcholine