Deletion of the Creatine Transporter ( Slc6a8 ) in Dopaminergic Neurons Leads to Hyperactivity in Mice

AbstractThe lack of cerebral creatine (Cr) causes intellectual disability and epilepsy. In addition, a significant portion of individuals with Cr transporter (Crt) deficiency (CTD), the leading cause of cerebral Cr deficiency syndromes (CCDS), are diagnosed with attention-deficit hyperactivity disorder. While the neurological effects of CTD are clear, the mechanisms that underlie these deficits are unknown. Part of this is due to the heterogenous nature of the brain and the unique metabolic demands of specific neuronal systems. Of particular interest related to Cr physiology are dopaminergic neurons, as many CCDS patients have ADHD and Cr has been implicated in dopamine-associated neurodegenerative disorders, such as Parkinson ’s and Huntington’s diseases. The purpose of this study was to examine the effect of a loss of theSlc6a8 (Crt) gene in dopamine transporter (Slc6a3; DAT) expressing cells on locomotor activity and motor function as the mice age. FloxedSlc6a8 (Slc6a8flox) mice were mated to DATIREScre expressing mice to generate DAT-specificSlc6a8 knockouts (dCrt−/y). Locomotor activity, spontaneous activity, and performance in the challenging beam test were evaluated monthly in dCrt−/y and control (Slc6a8flox) mice from 3 to 12  months of age. dCrt−/y mice were hyperactive compared with controls throughout testing. In addition, dCrt−/y mice showed increased rearing and hindlimb steps in the spontaneous activity test. Latency to cross the narrow bridge was i...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research