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You searched for +publisher:"The Ohio State University" +contributor:("Bishop, Georgia"). Showing records 1 – 2 of 2 total matches.

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The Ohio State University

1. Schmid, Cullen L. Differential regulation of serotonin 2A receptor responsiveness by agonist-directed interactions with beta-arrestin2.

Degree: PhD, Neuroscience Graduate Studies Program, 2011, The Ohio State University

The G protein-coupled, serotonin 2A (5-HT2A) receptor is a major drug target for the treatment of a number of mental health disorders, including schizophrenia, anxiety and depression. In addition to modulating several of the physiological effects of the neurotransmitter serotonin, activation of the 5-HT2A receptor mediates the psychotomimetic effects of serotonergic hallucinogenic drugs, such as lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-iodoamphetamine (DOI) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). Though hallucinogens are agonists at the 5-HT2A receptor, not all 5-HT2A receptor agonists induce hallucinations in humans, including the endogenous ligand serotonin. Therefore, the activation of the 5-HT2A receptor can result in different biological responses depending upon the chemical nature of the ligand, a concept that has been referred to as “functional selectivity.” One way in which ligands can induce differential signaling at GPCRs is through interactions with beta-arrestins, which can act to dampen or facilitate receptor signaling cascades or mediate the internalization of receptors into intracellular vesicles. The overarching hypothesis of this dissertation is that the interaction between the regulatory protein, beta-arrestin2, and the 5-HT2A receptor is a critical point in the divergence of agonist-directed 5-HT2A receptor responsiveness. Using mice lacking beta-arrestin2, we evaluate 5-HT2A receptor trafficking and signaling in vivo for serotonin, the hallucinogenic agonists DOI and 5-MeO-DMT and the endogenous, hallucinogenic metabolite of serotonin, N-methylserotonin. We find that beta-arrestin2 mediates 5-HT2A receptor trafficking in primary neuronal cultures and can facilitate 5-HT2A receptor-mediated signaling cascades in the mouse frontal cortex, although its role is entirely dependent upon the agonist acting at the receptor. Serotonin requires beta-arrestins to internalize the 5-HT2A receptor and to scaffold the signaling kinases Akt and Src to the receptor. The formation of this receptor scaffold results in an increase in Akt activity, which is disrupted in the absence of beta-arrestin2, while the reintroduction of beta-arrestin2 into primary cortical neurons rescues serotonin-induced phosphorylation of Akt. Moreover, the disruption of these cellular events, either by the absence of beta-arrestin2 or by inhibiting the kinases, results in the inability of serotonin to induce the head twitch response in mice, which is a behavioral model of 5-HT2A receptor activation in the mouse frontal cortex. In contrast, DOI maintains its ability to internalize the 5-HT2A receptor in the absence of beta-arrestin2 and DOI, 5-MeO-DMT and N-methylserotonin do not activate beta-arrestin2-mediated signaling cascades in mouse embryonic fibrobalsts, primary cortical neurons or the mouse frontal cortex. The activation of the head twitch response by these hallucinogenic agonists is not disrupted in beta-arrestin2-knockout mice or in the presence of inhibitors to Akt. Collectively, these studies advance our… Advisors/Committee Members: Bishop, Georgia (Advisor), Bohn, Laura (Advisor).

Subjects/Keywords: Neurosciences; Pharmacology; G protein-coupled receptor; Serotonin 2A receptor; beta-arrestin2; hallucinogens; functional selectivity

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Schmid, C. L. (2011). Differential regulation of serotonin 2A receptor responsiveness by agonist-directed interactions with beta-arrestin2. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1300287547

Chicago Manual of Style (16th Edition):

Schmid, Cullen L. “Differential regulation of serotonin 2A receptor responsiveness by agonist-directed interactions with beta-arrestin2.” 2011. Doctoral Dissertation, The Ohio State University. Accessed December 14, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1300287547.

MLA Handbook (7th Edition):

Schmid, Cullen L. “Differential regulation of serotonin 2A receptor responsiveness by agonist-directed interactions with beta-arrestin2.” 2011. Web. 14 Dec 2019.

Vancouver:

Schmid CL. Differential regulation of serotonin 2A receptor responsiveness by agonist-directed interactions with beta-arrestin2. [Internet] [Doctoral dissertation]. The Ohio State University; 2011. [cited 2019 Dec 14]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1300287547.

Council of Science Editors:

Schmid CL. Differential regulation of serotonin 2A receptor responsiveness by agonist-directed interactions with beta-arrestin2. [Doctoral Dissertation]. The Ohio State University; 2011. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1300287547


The Ohio State University

2. Emch, Gregory Simon. EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON DORSAL VAGAL COMPLEX NEURONS THAT EXERT REFLEX CONTROL OF THE GASTROINTESTINAL TRACT.

Degree: PhD, Neuroscience, 2002, The Ohio State University

The results of the experiments presented in this thesis have shown that injection of tumor necrosis factor-alpha (TNF) into the dorsal vagal complex [DVC; made up of the area postrema (AP), the sensory nucleus of the solitary tract (NST), and the dorsal motor nucleus of the vagus (DMN)] has mixed results on neuronal activity in this medullary brainstem area. In the NST, microinjection of TNF causes a significant and dose-dependent increase in neuronal firing rate (FR) as compared to injection of saline controls. Subsequently, some NST neurons exhibit a potentiated response to afferent stimulation following pre-exposure of the neurons to TNF. Conversely, microinjection of TNF significantly inhibits the FR of most neurons in the DMN. Immunohistochemical studies show that the protein product of the proto-oncogene c-Fos (a marker of neuronal activation) is increased in response to systemic administration of lipopolysaccharide (LPS; bacterial cell coat component that induces endogenous production of TNF) in the DVC. Additionally, protein expression is independent of the integrity of the vagus nerve(s). That is, surgical section of the vagi does not inhibit the increase in number of c-Fos labeled neurons. Direct injection of TNF into the NST causes a significant elevation of Fos-labeled neurons, and protein expression is dependent on glutamate neurotransmission since glutamate receptor antagonists abolish any significant increase in Fos-positive neurons evoked by injection of TNF alone. Therefore, it was concluded that tumor necrosis factor-alpha causes gastrointestinal stasis by removing cholinergic excitation to the stomach. TNF alters vago-vagal reflexes by acting directly on neurons at the level of the dorsal vagal complex in the medullary brainstem. Advisors/Committee Members: Bishop, Georgia (Advisor).

Subjects/Keywords: NST; TNF; VAGAL; c-Fos; NEURONS; gastric; DMN

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Emch, G. S. (2002). EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON DORSAL VAGAL COMPLEX NEURONS THAT EXERT REFLEX CONTROL OF THE GASTROINTESTINAL TRACT. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1018475175

Chicago Manual of Style (16th Edition):

Emch, Gregory Simon. “EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON DORSAL VAGAL COMPLEX NEURONS THAT EXERT REFLEX CONTROL OF THE GASTROINTESTINAL TRACT.” 2002. Doctoral Dissertation, The Ohio State University. Accessed December 14, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1018475175.

MLA Handbook (7th Edition):

Emch, Gregory Simon. “EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON DORSAL VAGAL COMPLEX NEURONS THAT EXERT REFLEX CONTROL OF THE GASTROINTESTINAL TRACT.” 2002. Web. 14 Dec 2019.

Vancouver:

Emch GS. EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON DORSAL VAGAL COMPLEX NEURONS THAT EXERT REFLEX CONTROL OF THE GASTROINTESTINAL TRACT. [Internet] [Doctoral dissertation]. The Ohio State University; 2002. [cited 2019 Dec 14]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1018475175.

Council of Science Editors:

Emch GS. EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON DORSAL VAGAL COMPLEX NEURONS THAT EXERT REFLEX CONTROL OF THE GASTROINTESTINAL TRACT. [Doctoral Dissertation]. The Ohio State University; 2002. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1018475175

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