In our laboratory, we recently developed a Cre-loxP transgenic model to specifically inactivate β-catenin in DA neurons of the ventral midbrain (β-catenin KO mice). β-catenin KO mice are born at expected Mendelian radios. Adult mice present lower body weight compared with age-matched controls. Stereological cell counts do not reveal differences in the number of tyrosine hydroxylase positive neurons in the substantia nigra and ventral tegmental area of β-catenin KO mice. However, behavioral studies showed that β-catenin deficient mice are hyperactive in a novel environment, although no changes were found in the circadian locomotor activity pattern. To assess the dynamics of DA release in the striatum, fast-scan cyclic voltammetric recordings were performed in brain slices obtained from β-catenin KO mice and WT controls. Preliminary studies showed an increase of DA release in the striatum of KO animals when compared to controls. Striatal prodynorphin (PDyn) mRNA levels were significantly elevated in KO animals, suggesting an enhancement in neuronal activity associated with the striatonigral projection pathway, while preproenkephalin (PPE) mRNA levels remained unchanged. These results suggest β-catenin plays an essential role in the development and maintenance of dopaminergic neurotransmission. Our lab is currently focused on elucidating what molecular mechanisms, mediated by β-catenin ablation, result in the observed changes in behavior and dopaminergic neurotransmission.
| Diaz-Ruiz, Oscar; Zhang, Yajun; Shan, Lufei et al. (2012) Attenuated response to methamphetamine sensitization and deficits in motor learning and memory after selective deletion of ýý-catenin in dopamine neurons. Learn Mem 19:341-50 |
