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Neuroprotection of Dopaminergic Neurons and their Subcellular Structures from Parkinson's Disease-like Treatment

Wiemerslage, Lyle N.
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1395669814

Abstract Details

2014, Doctor of Philosophy (PhD), Ohio University, Biological Sciences (Arts and Sciences).
In this dissertation, I explore the molecular mechanisms involved in the neuroprotection of dopaminergic (DA) neurons from Parkinson's disease (PD)-like treatment. PD is movement disorder characterized by the slow, gradual death of DA neurons in the substantia nigra pars compacta. Neuroprotection is the idea that these cells could be rescued or protected from pathology. I establish a Drosophila primary culture system to study PD-like neurodegeneration and screen potential neuroprotective therapies. DA neurons, as well as their subcellular structures, are quantified and compared between treatment groups. I show that1-methyl-4-phenylpyridinium (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), selectively damages DA neurons and their mitochondrial morphology. I also show that the dopamine type 2 (D2) receptor agonist quinpirole can prevent, but not reverse, MPP+-induced degeneration. Furthermore, I show that D2 autoreceptors (presynaptic receptors which respond to autologous DA release) are required for the rescue by quinpirole. However, even in DA neurons lacking D2 autoreceptors, MPP+-induced degeneration was prevented by reducing cellular excitability: either with the Na+-channel blocker tetrodotoxin (TTX) or by Ca2+ chelation. Moreover, DA neurons with mutated Ca2+ channels were inherently protected from MPP+ treatment. Lastly, I describe the time-course of MPP+-induced degeneration within this model system. DA neurons are near-completely post-mitotic by 3 days in vitro (DIV), which is the time point when cultures are treated with drugs. I find that damage to mitochondria precedes the death of DA neurons, and that rescue therapy must be given almost concomitantly with PD-inducing treatment to be effective.
Daewoo Lee (Advisor)
Robert Colvin (Committee Member)
Janet Duerr (Committee Member)
Howard Dewald (Committee Member)
142 p.
Biology; Molecular Biology; Neurobiology; Neurosciences
MPP; dopamine; neuron; mitochondria; morphology; Drosophila; calcium

Recommended Citations

Citations

  • Wiemerslage, L. N. (2014). Neuroprotection of Dopaminergic Neurons and their Subcellular Structures from Parkinson's Disease-like Treatment [Doctoral dissertation, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1395669814

    APA Style (7th edition)

  • Wiemerslage, Lyle. Neuroprotection of Dopaminergic Neurons and their Subcellular Structures from Parkinson's Disease-like Treatment . 2014. Ohio University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1395669814.

    MLA Style (8th edition)

  • Wiemerslage, Lyle. "Neuroprotection of Dopaminergic Neurons and their Subcellular Structures from Parkinson's Disease-like Treatment ." Doctoral dissertation, Ohio University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1395669814

    Chicago Manual of Style (17th edition)

ohiou1395669814
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© 2014, all rights reserved.
This open access ETD is published by Ohio University and OhioLINK.