Dissertation Goals Sample Clauses

Dissertation Goals. The purpose of the studies described in this dissertation were to identify functional roles for GPR37 and GPR37L1 in models of disease. Chapter 2 of the dissertation establishes an association between a variant in GPR37L1 (c.1047G>T [Lys349Asp]) with a novel progressive myoclonic epilepsy. Although no striking differences were observed between GPR37L1 and the K349N variant in transfected cells, loss of Gpr37L1 in vivo resulted in increased seizures susceptibility in two seizure induction paradigms. Additionally, mice lacking the closely related receptor, GPR37 also resulted in increased seizure susceptibility in a seizure induction paradigm and elicited spontaneous seizures. Finally, mice lacking both Gpr37 and Gpr37L1 are much more susceptible to seizures than single knockout mice and elicit significantly longer spontaneous seizures than mice lacking only GPR37. Chapter 3 discusses the role of GPR37 in models of ischemic stroke. It was found that loss of GPR37 results in a larger infarct volume after induction of focal cerebral ischemia. Interestingly, Gpr37 expression increases dramatically in the penumbra region following the middle cerebral artery occlusion (MCAO) model of ischemic stroke. Xxxxxxx, XXX00X0 expression is significantly reduced in the penumbra following MCAO in WT, but not Gpr37-/- mice. Loss of Gpr37 also resulted in attenuated expression of the hypoxia inducible factor 1α (HIF1α) and the astrocytic marker glial acidic fibrillary protein (GFAP), but not the microglial marker, ionized calcium-binding adapter molecule 1 (Iba1). Furthermore, primary astrocytes cultured from Gpr37-/- mice were more susceptible oxygen glucose deprivation, an in vitro model of stroke, than wild type (WT) astrocytes. The final chapter of this dissertation discusses the larger implications of the data presented in Chapters 2 and 3. CHAPTER 2: GPR37L1 Modulates Seizure Susceptibility: Evidence from Mouse Studies and Analyses of a Human GPR37L1 Variant This chapter is adapted in part from: Xxxxxxx, X.X., Xxxx, X.X., Xxxxxxxxx, X.X., Xxxxxx, E.G., Xxxxx, X.X., Owino, S., Xxxxx, X.X., Xxxxx, X.X., Xxxxxxxx, C., XxXxxxxx, X.X., Xxxxxxxxxxx, D., Xxxxxx, A., and Xxxx, X.X. GPR37L1 Modulates Seizure Susceptibility: Evidence from Mouse Studies and Analyses of a Human GPR37L1 Variant. Submitted. Author contributions: All trafficking, signaling and protein-protein interaction studies described in this chapter were designed by X.X. Xxxxxxx and X.X. Xxxx and performed by X.X...
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Dissertation Goals. The aim of this dissertation is to begin forming a general theory of agreement. We have four goals:
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Dissertation Goals. This dissertation will begin to fill in gaps in the understanding of oxytocin circuitry and how it is involved in affiliative behaviors in female prairie voles. In chapter 2, I investigate the hypothesis that differences in OTR density in the NAcc directly contributes to individual differences in affiliative behaviors. By using an adeno- associated viral vector carrying the prairie vole OTR gene, the levels of OTR in the NAcc of adult female prairie voles was increased. These females were then tested for alloparental and partner preference behaviors. Accumbal OTR was also increased in female meadow voles to determine if OTR in this reward area can influence affiliative behavior in a non-monagoumous species. In chapter 3, we characterized the oxytocin system that influences these affiliative behaviors by using retrograde tract tracing, immunohistochemistry, and electron microscopy. I conclude this thesis by discussing how the central OT system may be organized to promote the coordination of peripheral physiology and behavioral changes associated with reproduction. CHAPTER 2 Variation in Oxytocin Receptor Density in the Nucleus Accumbens has Differential Effects on Affiliative Behaviors in Monogamous and Polygamous Voles This chapter presents work published as: Xxxx HE, Xxxxxxx XX, Xxxxxxx LL, Ren X, Xxxxxxxxxxx E, and XX Xxxxx. 2009. Variation in oxytocin receptor density in the nucleus accumbens has differential effects on affiliative behaviors in monogamous and polygamous voles. J Neurosci. Feb 4;29(5):3112-3119.
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