Résumé
Myostatin plays crucial roles in negative regulation of muscle growth. Inactivation of the myostatin gene results in gross muscle hypertrophy. We observed that myostatin knock-out (myostatin-KO) mice are more aggressive than wild-type (WT) mice. Ghrelin is a hormone produced by cells of the gastrointestinal tract that activates cells in the brain and increases the drive to eat. The level of circulating ghrelin affects anxiety, stress, and aggression. Ghrelin controls expression of myostatin in disease-associated cachexia. Butyrylcholinesterase (BChE) is responsible for the deacylation of ghrelin. BChE knock-out mice show higher level of acylated ghrelin and are more aggressive than WT mice. De-acylation of ghrelin by BChE reduces aggression in mice. We hypothesized that the levels of expression of BChE, ghrelin and myostatin could explain the aggressive behavior of myostatin-myostatin-KO mice. Resident/intruder tests shows that male myostatin-KO mice are more aggressive than WT littermates. Female myostatin-KO mice show much higher spontaneous exercise than female WT and males of both genotypes. Behavioral tests (elevated plus maze and light/dark box) show that myostatin-KO mice present anxious behavior without any change in circulating corticosterone. Myostatin-KO mice have a lower acylated/unacylated ghrelin ratio. Female myostatin-KO mice show lower level of BChE activity compared with WT littermates. Comparison of staining for various neurotransmitter systems involved in behavior showed that the only region where there was a difference between WT and myostatin-KO mice was in the habenular complex which involved in regulation of behavior. Reduced ghrelin levels and loss of parvalbumin neurons of the habenular complex could partly explain the behavior of our model.
•Male myostatin-KO mice are more aggressive than wild-type, and KO mice of both sexes are more stressed.•Female myostatin-KO mice show greater spontaneous exercise than WT.•Absence of myostatin reduces the plasmatic ratio of acylated/unacylated ghrelin in myostatin KO mice.•BChE levels are similar in mice but levels of BChE transcripts in hypothalamus are elevated in female myostatin-KO mice.•In myostatin-KO mice, loss of parvalbumin in the habenula may be important in behavioral regulation.