Knock‐down of Vmat2 in Mouse Right Striatum and Physical Activity

Abstract

In spite of significant evidence that daily activity is controlled primarily by genetic mechanisms, there is little data available regarding the mechanisms of action. We investigated the role of vesicular monomine transporter type 2 (Vmat2) in regulating wheel‐running activity in mice and to determine the time course of gene silencing using vivo‐morpholinos. All aspects of this study were conducted in conformance with the FASEB Statement of Principles for the use of animals in research and education. We randomly assigned 24, 8 week old male C57Bl/6J mice to one of two groups: an access to running wheel group and a fixed running wheel group. All animals received a tail‐vein injection (11mg/kg) of Vmat2‐targeted vivo‐morpholino for three consecutive days. One mouse from each group was sacrificed each day. Western Blotting was used to track efficacy of gene knock‐down. Vmat2 expression decreased with morpholino injection, but no differences were found between wheel and fixed wheel groups (p=0.29). Physical activity was initially decreased after Vmat2 knock‐down (days 1–5), with activity on days 6–10 significantly increasing (p=0.0016) toward baseline values. In conclusion wheel exposure did not affect efficacy of Vmat2 knock‐down. Further, transiently silencing Vmat2 resulted in a transient decrease in physical activity suggesting that Vmat2 may play a role in regulating activity.