Establishment of a survival and toxic cellular model for Parkinson's disease from chicken mesencephalon.

Cellular models for Parkinson's disease (PD) represent a fast and efficient tool in the screening for drug candidates and factors involved in the disease pathogenesis. The objective of this study was to establish and characterize a survival and toxic cellular model for PD by culturing dopaminergic neurons from embryonic chicken ventral midbrain. We show that as in rodents, the common neurotrophic factors--brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and fibroblast growth factor 2 (FGF2)--are able to support the survival of chicken midbrain dopaminergic neurons. Furthermore, after treatment with MPP⁺ or rotenone as in vitro models for PD, the number of tyrosine hydroxylase-positive cells decreased drastically. This effect could be significantly rescued by treatment with BDNF or GDNF. Together, our results indicate that mechanisms of neuroprotection of dopaminergic neurons are conserved between chicken and mammals. This supports the use of primary culture from chicken embryonic midbrain as a suitable tool for the study of neuroprotection in vitro.

Gene structure and evolution of Tieg3, a new member of the Tieg family of proteins.

TGF beta-inducible immediate early gene, Tieg, belongs to the superfamily of Sp1-like transcription factors containing three C(2)H(2)-zinc finger DNA binding motifs close to the C-terminus. So far, Tieg1 and Tieg2 have been identified in human and mouse. We identified Tieg3, a new member of the Tieg protein family by screening a mouse cDNA library. Tieg3 has almost all the known features of the Tieg protein family: it shares a highly conserved C(2)H(2) zinc finger DNA binding domain and is 96% identical to Tieg2 and 86% to Tieg1, respectively. In addition, the three repression domains at the N-terminus, R1, R2 and R3 are conserved in all the Tiegs. Similar to Tieg1 and Tieg2, Tieg3 mRNA is up-regulated in response to TGF beta 1 treatment and can perform the Sp1 sites mediated repression of transcription. A 4 kilobase (kb) long transcript of mouse Tieg3 can be detected using Northern-blot analysis. The gene of mouse Tieg3 contains four exons. Due to the amino acid sequence similarity, mouse Tieg2 is regarded as an orthologue of human Tieg2. However, the mouse Tieg3 gene is localized in a conserved segment on mouse chromosome 12 corresponding to human Tieg2 on chromosome 2 with the same gene order. An interesting explanation for this apparent contradiction might be a homologous recombination leading to loci exchange between the mouse Tieg3 and Tieg2.