| First Author | Yohrling GJ 4th | Year | 2003 |
| Journal | Brain Res Mol Brain Res | Volume | 119 |
| Issue | 1 | Pages | 28-36 |
| PubMed ID | 14597227 | Mgi Jnum | J:132442 |
| Mgi Id | MGI:3775970 | Doi | 10.1016/j.molbrainres.2003.08.009 |
| Citation | Yohrling GJ 4th, et al. (2003) Analysis of cellular, transgenic and human models of Huntington's disease reveals tyrosine hydroxylase alterations and substantia nigra neuropathology. Brain Res Mol Brain Res 119(1):28-36 |
| abstractText | Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative disorder that is pathologically characterized by a striatal-specific degeneration. Aberrant dopamine neurotransmission has been proposed as a mechanism underlying the movement disorder of HD. We report that the enzymatic activity of tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine biosynthesis, is decreased in a transgenic mouse model of HD. In addition, mutant huntingtin was found to disrupt transcription of TH and dopamine beta-hydroxylase (DbetaH) promoter reporter constructs. In situ hybridization revealed extensive loss of TH mRNA and decreased dopaminergic cell size in human HD substantia nigra. TH-immunoreactive protein was reduced in human grade 4 HD substantia nigra by 32% compared to age-matched controls. These findings implicate abnormalities in dopamine neurotransmission in HD and may provide new insights into targets for pharmacotherapy. |
