On the Mechanism of Neurotoxicity from Methamphetamine: The Role of Neuropeptide Y
Item
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Title
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On the Mechanism of Neurotoxicity from Methamphetamine: The Role of Neuropeptide Y
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Identifier
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d_2009_2013:59418a36b3b3:11261
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identifier
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11628
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Creator
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Yarosh, Haley,
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Contributor
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Jesus A. Angulo
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Date
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2012
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Language
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English
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Publisher
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City University of New York.
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Subject
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Neurosciences | Toxicology | methamphetamine | neuropeptide Y | striatum | toxicity
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Abstract
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The purpose of this study is to describe the potential neuroprotective effect of neuropeptide Y in response to striatal nitric oxide overproduction after methamphetamine (METH) use. Our lab has established a time course and optimal dosage for modeling acute METH neurotoxicity in the murine brain. A 30 mg/kg systemic injection of METH depletes intracellular dopamine and serotonin levels, and induces dopamine receptor endocytosis as well cell loss of approximately 30% of striatal neurons.;Dopamine overflow from presynaptic terminals paired with glutamate signaling from the cerebral cortex commences a neuronal cascade, which leads to the overproduction of nitric oxide, inflammatory cytokines and reactive oxidative/nitrogen byproducts. We observe that when neuropeptide Y (Y1R, Y2R) agonists are administered prior to METH, the appearance of apoptotic cells and neurodegeneration markers are attenuated. Additionally, there is an endogenous upregulation of striatal neuropeptide Y mRNA stores during the early hours after METH administration.;The following study establishes an optimal dose and time course for neuropeptide Y induction, and suggests that neuropeptides are at play to establish homeostasis after acute METH toxicity. We characterize the cellular response to METH-induced nitric oxide production through fluorescent co-label, and demonstrate that the effect of neuropeptide Y on these cell types is modulated by specific neuropeptide Y receptors. The neuroprotective effect of NPY persists even in the presence of substance P agonists, associated with exacerbation of methamphetamine-induced neurotoxicity.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Biology
