Knockdown of @entity14019 protein levels normalizes neuronal activity in a XXXX model of @entity191 .

@entity935 @entity191 @entity9774 @entity14019 @entity35
BACKGROUND: @entity935 depletion of the striatum is one of the hallmarks of @entity191 . The loss of @entity935 upregulates @entity14019 expression in the striatal projection neurons and causes other changes in the activity of the basal ganglia circuit. METHODS: To normalize the @entity14019 expression in the striatum after @entity935 depletion, we developed several lentiviral vectors that express RNA interference (RNAi) directed against @entity14019 mitochondrial RNA. The vectors were injected into the striatum of hemiparkinsonian @entity35 and the level of @entity14019 protein as well as a marker of neuronal activity, @entity9774 , was analyzed using western blots. RESULTS: Unilateral lesions of the @entity935 neurons in substantia nigra resulted in an increased level of @entity14019 protein in the ipsilateral striatum. Furthermore, we detected significantly higher levels of @entity9774 , after @entity935 depletion in the striatum. Using a lentiviral vectors with a synthetic miRNA scaffold to deliver RNAi, we were able to normalize the @entity14019 protein levels in the @entity191 @entity35 striatum. In addition, we were able to normalize the increased neural activity, which resulted from the loss of @entity935 as measured by the marker @entity9774 . CONCLUSIONS: We conclude that RNAi directed against @entity14019 may be a valid approach to correct the dysregulation of the basal ganglia circuit in a @entity35 model of @entity191 . The possibility to correct for a loss of @entity935 using nondopamimetic tools is interesting because it may be more directed towards the casual mechanisms of the motor symptoms.
