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You searched for +publisher:"Temple University" +contributor:("Sapru, Hreday N."). Showing records 1 – 3 of 3 total matches.

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Temple University

1. Deliu, Elena. GPER/GPR30 Estrogen Receptor: A Target for Pain Modulation.

Degree: PhD, 2012, Temple University

Pharmacology

The G protein-coupled estrogen receptor GPER/GPER1, also known as GPR30, was originally cloned as an orphan receptor and later shown to be specifically activated by 17-ß-estradiol. This has led to its classification as an estrogen receptor and expanded the perspective on the mechanisms underlying the rapid estrogenic effects reported over the years. GPER is strongly expressed in the central nervous system and peripheral tissues and appears to be involved in a wide variety of physiological and pathological processes. Estrogens are known to alter the processing of nociceptive sensory information and analgesic responses in the central nervous system. Both analgesic and pro-nociceptive effects of estrogens have been reported. Some pro-algesic estrogenic responses have a short latency, suggesting a non-genomic mechanism of action. Immunohistochemical studies in rodents prove the existence of GPER in pain-relevant areas of the nervous system such as dorsal root ganglia, superficial dorsal horn of the spinal cord, periaqueductal gray (PAG), amygdala, trigeminal sensory nucleus and thalamus. In the periphery, activation of GPER results in pro-nociceptive effects. However, GPER involvement in pain processing at central levels is largely unexplored. Thus, the work presented in this thesis was aimed at investigating whether GPER modulates nociception at spinal and supraspinal sites. The behavioral response to GPER activation in the spinal cord and PAG was evaluated in an acute grooming test (scratching, biting and licking behavior) and in the hot plate test, respectively. Intrathecal challenge of mice with the GPER agonist G-1 (0.1-1 nmol) induced a dose-dependent increase in pain-related behaviors, that was abolished by pre-treatment with the GPER antagonist G15 (1-10 nmol), confirming GPER specificity of the response. Likewise, intra-PAG microinjection of G-1 (10-100 pmol) to rats reduced the nociceptive threshold in the hot plate test, an effect that was G15 sensitive. To obtain further insight on the mechanisms involved in the behavioral effects observed in whole animals, we tested the effect of GPER ligands on neuronal membrane potential, intracellular calcium concentration ([Ca2+]i) and reactive oxygen species (ROS) accumulation. The membrane depolarization and the increases in [Ca2+]i and ROS levels are markers of neuronal activation, underlying pain sensitization in the spinal cord and pain facilitation in the PAG. Electrophysiological recordings from superficial dorsal horn and lateral PAG neurons indicate neuronal depolarization upon G-1 application, an effect that was fully prevented by G15 pre-treatment. Both cultured spinal neurons and cultured PAG neurons responded to G-1 administration by elevating [Ca2+]i and mitochondrial and cytosolic ROS levels. In the presence of G15, G-1 did not elicit the calcium and ROS responses. Collectively, these results demonstrate that GPER modulates both the ascending and descending pain pathways to increase nociception via cytosolic calcium elevation and ROS…

Advisors/Committee Members: Dun, Nae J., Abood, Mary Ellen, Ashby, Barrie, Brailoiu, Eugen, Unterwald, Ellen M., Sapru, Hreday N..

Subjects/Keywords: Pharmacology; Biochemistry; calcium imaging; estrogen; gpr30; pain; reactive oxygen species

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APA (6th Edition):

Deliu, E. (2012). GPER/GPR30 Estrogen Receptor: A Target for Pain Modulation. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,194862

Chicago Manual of Style (16th Edition):

Deliu, Elena. “GPER/GPR30 Estrogen Receptor: A Target for Pain Modulation.” 2012. Doctoral Dissertation, Temple University. Accessed April 08, 2020. http://digital.library.temple.edu/u?/p245801coll10,194862.

MLA Handbook (7th Edition):

Deliu, Elena. “GPER/GPR30 Estrogen Receptor: A Target for Pain Modulation.” 2012. Web. 08 Apr 2020.

Vancouver:

Deliu E. GPER/GPR30 Estrogen Receptor: A Target for Pain Modulation. [Internet] [Doctoral dissertation]. Temple University; 2012. [cited 2020 Apr 08]. Available from: http://digital.library.temple.edu/u?/p245801coll10,194862.

Council of Science Editors:

Deliu E. GPER/GPR30 Estrogen Receptor: A Target for Pain Modulation. [Doctoral Dissertation]. Temple University; 2012. Available from: http://digital.library.temple.edu/u?/p245801coll10,194862


Temple University

2. Huang, Xiaofang. Functional study of amylin and regulation of amylin receptor.

Degree: PhD, 2010, Temple University

Pharmacology

Amylin, a 37 amino acid peptide secreted from pancreatic beta cells upon stimulation by meal/glucose, belongs to the family of the calcitonin or calcitonin gene-related peptide (CGRP) and shares up to 50% homology with CGRP, which is a well-documented pain-related peptide. The amylin receptor is composed of a calcitonin receptor (CTR) and receptor activity modifying proteins (RAMPs). Numerous studies have shown that amylin plays an important role in glucose homeostasis and food intake. Few studies have been conducted with respect to the effect of amylin in the central or peripheral neuraxis. In this thesis, immunohistochemical study revealed a dense network of amylin-immunoreactive (irAMY) cell processes in the superficial dorsal horn of the mice. Numerous dorsal root ganglion and trigeminal ganglion cells expressed moderate to strong irAMY. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed amylin receptor mRNA in the mouse spinal cord, brain stem, cortex, hypothalamus and hippocampus. The nociceptive or antinociceptive effects of amylin were evaluated in the tail flick and acetic acid-induced writhing test. Amylin (1-10 µg, i.t.) reduced the number of writhing in a dose-dependent manner. Pretreatment of the mice with the amylin receptor antagonist salmon calcitonin (8-32) [sCT(8-32)]or AC187 by i.t. antagonized the effect of amylin on acetic acid-induced writhing test. Locomotor activity was not significantly modified by amylin injected either i.p. (0.01-1 mg/kg) or i.t. (1-10 µg). Measurement of c-fos mRNA by RT-PCR or proteins by Western blot showed that the levels were up-regulated in the spinal cord of mice in acetic acid-induced visceral pain model and the increase was attenuated by pretreatment with amylin. Pretreatment of sCT[8-32] or AC187 significantly reversed the effect of amylin on c-fos expression in the spinal cord. As the neuronal response to amylin is closely dependent on the molecular property of amylin receptor, the localization, internalization and regulation of the calcitonin and amylin receptor were examined in the second part of the thesis. Immunofluorescence microscopy demonstrated the surface expression of CTRa, and intracellular distribution of RAMP1. Moreover, co-expression of CTRa translocated the RAMP1 to the cell surface and generated the amylin receptor phenotype. Both immunocytochemistry and on cell western analysis showed the internalization of CTRa and amylin receptor (CTRa/RAMP1) stimulated by different agonists, which was partially ß-arrestin dependent. Moreover, RAMP1 did not change the surface expression pattern of CTRa, but co-localized with the receptor with and without agonist treatment. sCT and amylin activated the ERK1/2 in HEK293 cells stably expressing amylin receptors, indicating the involvement of MAPK in amylin receptor signaling cascade. Collectively, these results led us to conclude that 1) irAMY is expressed in dorsal root ganglion neurons with their cell processes projecting to the superficial layers of the dorsal horn, and that the…

Advisors/Committee Members: Dun, Nae J., Ashby, Barrie, Chan, Marion M., Cowan, Alan, Liu-Chen, Lee-Yuan, Sapru, Hreday N..

Subjects/Keywords: Pharmacology; amylin; antinociceptive; calcitonin receptor; RAMP; spinal cord

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

APA (6th Edition):

Huang, X. (2010). Functional study of amylin and regulation of amylin receptor. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,114036

Chicago Manual of Style (16th Edition):

Huang, Xiaofang. “Functional study of amylin and regulation of amylin receptor.” 2010. Doctoral Dissertation, Temple University. Accessed April 08, 2020. http://digital.library.temple.edu/u?/p245801coll10,114036.

MLA Handbook (7th Edition):

Huang, Xiaofang. “Functional study of amylin and regulation of amylin receptor.” 2010. Web. 08 Apr 2020.

Vancouver:

Huang X. Functional study of amylin and regulation of amylin receptor. [Internet] [Doctoral dissertation]. Temple University; 2010. [cited 2020 Apr 08]. Available from: http://digital.library.temple.edu/u?/p245801coll10,114036.

Council of Science Editors:

Huang X. Functional study of amylin and regulation of amylin receptor. [Doctoral Dissertation]. Temple University; 2010. Available from: http://digital.library.temple.edu/u?/p245801coll10,114036


Temple University

3. Yang, Fan. Amylin mediates brainstem control of heart rate in the diving reflex.

Degree: PhD, 2012, Temple University

Pharmacology

Amylin, or islet amyloid polypeptide is a 37-amino acid member of the calcitonin peptide family. Amylin role in the brainstem and its function in regulating heart rates is unknown. The diving reflex is a powerful autonomic reflex, however no neuropeptides have been described to modulate its function. In this thesis study, amylin expression in the brainstem involving pathways between the trigeminal ganglion and the nucleus ambiguus was visualized and characterized using immunohistochemistry. Its functional role in slowing heart rate and also its involvement in the diving reflex were elucidated using stereotaxic microinjection, whole-cel patch-clamp, and a rat diving model. Immunohistochemical and tract tracing studies in rats revealed amylin expression in trigeminal ganglion cells, which also contained vesicular glutamate transporter 2 positive. With respect to the brainstem, amylin containing fibers were discovered in spinal trigeminal tracts. These fibers curved dorsally toward choline acetyltransferase immunoreactive neurons of the nucleus ambiguus, suggesting that amylin may synapse to parasympathetic preganglionic neurons in the nucleus ambiguus. Microinjection of fluorogold to the nucleus ambiguus retrogradely labeled a population of trigeminal ganglion neurons; some of which also contained amylin. In urethane-anesthetized rats, stereotaxic microinjections of amylin to the nucleus ambiguus caused a dose-dependent bradycardia that was reversibly attenuated by microinjections of the selective amylin receptor antagonist, salmon calcitonin (8-32) (sCT (8-32)) or AC187, and abolished by bilateral vagotomy. In an anesthetized rat diving model, diving bradycardia was attenuated by glutamate receptor antagonists CNQX and AP5, and was further suppressed by AC187. Whole-cel patch-clamp recordings from cardiac preganglionic vagal neurons revealed that amylin depolarizes neurons while decreasing conductance. Amylin also resulted in a reduction in whole cell currents, consistent with the decrease in conductance. Amylin is also found to increase excitability of neurons. In the presence of TTX, spontaneous currents in cardiac preganglionic vagal neurons were observed to decrease in frequency in response to amylin while amplitude remained constant, signifying that amylin reduces presynaptic activity at cardiac preganglionic vagal neurons. Finally, evoked synaptic currents revealed that amylin decreases evoked currents, further demonstrating that amylin depolarization and increase in excitability of cardiac preganglionic vagal neurons is also associated with simultaneous inhibition of presynaptic transmission. Our study has demonstrated for the first time that the bradycardia elicited by the diving reflex is mediated by amylin from trigeminal ganglion cells projecting to cardiac preganglionic neurons in the nucleus ambiguus. Additionally, amylin results in the depolarization and increased excitability of cardiac preganglionic vagal neurons while inhibiting presynaptic transmission.

Temple University – Theses

Advisors/Committee Members: Dun, Nae J., Cowan, Alan, Liu-Chen, Lee-Yuan, Brailoiu, Gabriela C., Chong, Parkson Lee-Gau, Sapru, Hreday N..

Subjects/Keywords: Pharmacology; Neurosciences; amylin; bradycardia; diving reflex; neuropeptide; nucleus ambiguus; trigeminal ganglion

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

APA (6th Edition):

Yang, F. (2012). Amylin mediates brainstem control of heart rate in the diving reflex. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,193415

Chicago Manual of Style (16th Edition):

Yang, Fan. “Amylin mediates brainstem control of heart rate in the diving reflex.” 2012. Doctoral Dissertation, Temple University. Accessed April 08, 2020. http://digital.library.temple.edu/u?/p245801coll10,193415.

MLA Handbook (7th Edition):

Yang, Fan. “Amylin mediates brainstem control of heart rate in the diving reflex.” 2012. Web. 08 Apr 2020.

Vancouver:

Yang F. Amylin mediates brainstem control of heart rate in the diving reflex. [Internet] [Doctoral dissertation]. Temple University; 2012. [cited 2020 Apr 08]. Available from: http://digital.library.temple.edu/u?/p245801coll10,193415.

Council of Science Editors:

Yang F. Amylin mediates brainstem control of heart rate in the diving reflex. [Doctoral Dissertation]. Temple University; 2012. Available from: http://digital.library.temple.edu/u?/p245801coll10,193415

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