Premium
Mice with selective elimination of striatal acetylcholine release are lean, show altered energy homeostasis and changed sleep/wake cycle
Author(s) -
Guzman Monica S.,
Jaeger Xavier,
Drangova Maria,
Prado Marco A. M.,
Gros Robert,
Prado Vania F.
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12128
Subject(s) - vesicular acetylcholine transporter , cholinergic , endocrinology , medicine , acetylcholine , striatum , biology , leptin , homeostasis , energy homeostasis , choline acetyltransferase , dopamine , obesity
Cholinergic neurons are known to regulate striatal circuits; however, striatal‐dependent physiological outcomes influenced by acetylcholine ( AC h) are still poorly under;?>stood. Here, we used vesicular acetylcholine transporter ( VAC hT) D2‐Cre‐flox/flox mice, in which we selectively ablated the vesicular acetylcholine transporter in the striatum to dissect the specific roles of striatal AC h in metabolic homeostasis. We report that VAC h T 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 VAC h T D 2‐Cre‐flox/flox mice showed increased physical activity. Interestingly, VAC h T 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 AC h 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.