Aktuelle Neurologie 2009; 36 - V298
DOI: 10.1055/s-0029-1238465

Striatal tyrosine hydroxylase expressing neurons in mouse models of Parkinson's disease

C Depboylu 1, WH Chiu 1, E Weihe 1, V Ries 1, WH Oertel 1, GU Höglinger 1, M Schäfer 1
  • 1Marburg

Tyrosine hydroxylase (TH) expressing neurons were identified in human and monkey striatum and reported to be regulated by dopamine depletion. Only few studies in rodents exist demonstrating transient appearance of TH+ neurons in the striatum after nigrostriatal dopaminergic injury. Using in situ hybridization we found that in mouse brain a subpopulation of striatal neurons express TH mRNA constitutively. After systemic application of the dopaminergic toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) the number of striatal TH+ neurons was not significantly changed as compared to saline treated control mice although the number of nigral TH+ neurons and their striatal projections decreased after MPTP treatment. However, after unilateral stereotactic lesioning of the medial forebrain bundle using 6-OHDA the number of TH+ neurons in the completely deafferentiated striatum increased over time as compared to the contralateral unlesioned side. The increase of TH+ neurons was neither a result of neurogenesis (no BrdU incorporation) nor differentiation of preexisting neuroblasts (no costaining for Nestin, PSA-NCAM and Doublecortin). These striatal TH+ neurons were identified as interneurons exhibiting immunoreactivity for glutamate decarboxylase (GAD) and dopamine- and cAMP-regulated phosphoprotein-32 (DARPP32). The dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2) and the serine-phosphorylated isoforms of TH (THpS19, THpS31, THpS40) could not be detected in any of these striatal TH+ neurons. A subpopulation of these neurons were positive for aromatic acid decarboxylase (AADC). The specific molecular phenotype of these neurons and their role in the intrastriatal and nigrostriatal circuitry needs further investigation to properly employ these incomplete dopaminergic phenotype for therapeutic strategies in the treatment of Parkinson's disease and other basal ganglia disorders.