| First Author | Gonzalez-Alegre P | Year | 2019 |
| Journal | Neuroscience | Volume | 422 |
| Pages | 1-11 | PubMed ID | 31669362 |
| Mgi Jnum | J:285560 | Mgi Id | MGI:6391735 |
| Doi | 10.1016/j.neuroscience.2019.09.007 | Citation | Gonzalez-Alegre P, et al. (2019) A Novel Transgenic Mouse Model to Investigate the Cell-Autonomous Effects of torsinA(DeltaE) Expression in Striatal Output Neurons. Neuroscience 422:1-11 |
| abstractText | Dystonia is a disabling neurological syndrome characterized by abnormal movements and postures that result from intermittent or sustained involuntary muscle contractions; mutations of DYT1/TOR1A are the most common cause of childhood-onset, generalized, inherited dystonia. Patient and mouse model data strongly support dysregulation of the nigrostriatal dopamine neurotransmission circuit in the presence of the DYT1-causing mutation. To determine striatal medium spiny neuron (MSN) cell-autonomous and non-cell autonomous effects relevant to dopamine transmission, we created a transgenic mouse in which expression of mutant torsinA in forebrain is restricted to MSNs. We assayed electrically evoked and cocaine-enhanced dopamine release and locomotor activity, dopamine uptake, gene expression of dopamine-associated neuropeptides and receptors, and response to the muscarinic cholinergic antagonist, trihexyphenidyl. We found that over-expression of mutant torsinA in MSNs produces complex cell-autonomous and non-cell autonomous alterations in nigrostriatal dopaminergic and intrastriatal cholinergic function, similar to that found in pan-cellular DYT1 mouse models. These data introduce targets for future studies to identify which are causative and which are compensatory in DYT1 dystonia, and thereby aid in defining appropriate therapies. |
