<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "The role of KATP channels in model systems of dopaminergic neuron loss in the ventral mesencephalon"^^ . "The dopaminergic neurons of the ventral midbrain (mesDA neurons) form several distinct sub-populations which are involved in emotional control, reward behavior and motor control. In patients with the neurodegenerative disorder Parkinsons Disease (PD), one of these groups, the dopaminergic neurons of the substantia nigra, pars compacta (SNpc) gradually die. One focus of research has been to find an explanation why the SNpc neurons are more vulnerable to cellular stress than other neuronal populations. In engrailed mutant mice, the absence of the homebox transcription factors engrailed 1 and engrailed 2 (En1 and 2) causes a cell-autonomous and gene-dose dependent loss of mesDA neurons. Recently, our lab identified several genes differentially expressed between wild-type and engrailed mutant mice. Analysis of mouse mutants of one of the genes, the forkhead containing trancription factor 1, Foxa1 (formerly HNF3α) showed no phenotype in regard to the mesDA neurons. As it is well known that members of the Fox/HNF family of genes can compensate for each other, we focused our research on one downstream target of Fox genes, the expression of KATP channels in mesDA neurons. KATP channels consist of Sur1 or 2 and Kir6.1 or 6.2 subunits and link the metabolic state of a cell to its membrane potential. Our hypothesis was, that misregulation or impairment of these channels may lead to an increased electrical activity of the mesDA cells, putting them under heightened physiological stress which then may in turn cause cell death. Analysis of both Sur1 and Kir6.2 mouse mutants showed no change in TH+ cell number, cell density or density of axonal projections, thus a loss of functional KATP channels has no effect on the survival of mesDA neurons. After Liss and colleagues found a decreased cell loss when Kir6.2 mutant mesDA cells suffer a toxin insult, we revised our hypothesis and postulated that the normal open-closed state of KATP channels influences cellular survival when the cell is under oxidative stress. In this work, I show that blocking KATP channels in vitro by pharmaceutical means has a positive effect on cell survival when mesDA are under oxidative stress. Conversely, forced activation of KATP channels under these conditions leads to an increased rate of cell death. Furthermore, abolishment of KATP channel expression in En1-/+:En2-/- mice leads to a complete rescue of the mesDA cell of the SNpc. This highlights the importance of KATP channel function and may give a new direction in the development of drugs targeting Parkinsons disease."^^ . "2007" . . . . . . . . "Christian"^^ . "Scholz"^^ . "Christian Scholz"^^ . . . . . . "The role of KATP channels in model systems of dopaminergic neuron loss in the ventral mesencephalon (PDF)"^^ . . . "Thesis.pdf"^^ . . . "The role of KATP channels in model systems of dopaminergic neuron loss in the ventral mesencephalon (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "The role of KATP channels in model systems of dopaminergic neuron loss in the ventral mesencephalon (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "The role of KATP channels in model systems of dopaminergic neuron loss in the ventral mesencephalon (Other)"^^ . . . . . . "preview.jpg"^^ . . . "The role of KATP channels in model systems of dopaminergic neuron loss in the ventral mesencephalon (Other)"^^ . . . . . . "medium.jpg"^^ . . . "The role of KATP channels in model systems of dopaminergic neuron loss in the ventral mesencephalon (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #8080 \n\nThe role of KATP channels in model systems of dopaminergic neuron loss in the ventral mesencephalon\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .