| First Author | Kholodilov N | Year | 2011 |
| Journal | J Neurochem | Volume | 116 |
| Issue | 4 | Pages | 486-98 |
| PubMed ID | 21133924 | Mgi Jnum | J:170428 |
| Mgi Id | MGI:4946474 | Doi | 10.1111/j.1471-4159.2010.07128.x |
| Citation | Kholodilov N, et al. (2011) Glial cell line-derived neurotrophic factor receptor-alpha1 expressed in striatum in trans regulates development and injury response of dopamine neurons of the substantia nigra. J Neurochem 116(4):486-98 |
| abstractText | Many of the cellular effects of glial cell line-derived neurotrophic factor are initiated by binding to GNDF family receptor alpha-1 (GFRalpha1), and mediated by diverse intracellular signaling pathways, most notably through the Ret tyrosine kinase. Ret may be activated by the cell autonomous expression of GFRalpha1 ('in cis'), or by its non-cell autonomous presence ('in trans'), in either a soluble or immobilized state. GFRalpha1 is expressed in the striatum, a target of the dopaminergic projection of the substantia nigra. To determine whether post-synaptic expression of GFRalpha1 in striatum in trans has effects on the development or adult responses to injury of dopamine neurons, we have created transgenic mice in which GFRalpha1 expression is selectively increased in striatum and other forebrain targets of the dopaminergic projection. Post-synaptic GFRalpha1 has profound effects on the development of dopamine neurons, resulting in a 40% increase in their adult number. This morphologic effect was associated with an augmented motor response to amphetamine. In adult mice, post-synaptic GFRalpha1 expression did not affect neuron survival following neurotoxic lesion, but it did increase the preservation of striatal dopaminergic innervation. We conclude that post-synaptic striatal GFRalpha1 expression has important effects on the biology of dopamine neurons in vivo. |
