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You searched for +publisher:"Temple University" +contributor:("Brailoiu, Eugen"). Showing records 1 – 2 of 2 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 · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

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 October 27, 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. 27 Oct 2020.

Vancouver:

Deliu E. GPER/GPR30 Estrogen Receptor: A Target for Pain Modulation. [Internet] [Doctoral dissertation]. Temple University; 2012. [cited 2020 Oct 27]. 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. Heinisch, Silke. Chemokine interactions with the serotonin and opioid systems: anatomical and electrophysiological studies in the rat brain.

Degree: PhD, 2008, Temple University

Anatomy

Chemokines, immune proteins that induce chemotaxis and adhesion, and their G-protein coupled receptors distribute throughout the central nervous system (CNS), regulate neuronal patterning, and mediate neuropathology. These chemo-attractant molecules may provide a neuro-immune "link" by regulating CNS systems. The purpose of this study was to investigate the interactions of specific chemokines, stromal cell-derived factor (SDF)-1a/CXCL12, and fractalkine/CX3CL1, and their receptors, CXCR4 and CX3CR1, with the serotonin (5-hydroxytryptamine; 5-HT) and opioid systems using anatomical and electrophysiological techniques in the rat brain. In the serotonin dense midbrain raphe nuclei (RN), SDF-1a, CXCR4, fractalkine and CX3CR1 co-localize over 70% with 5-HT neurons. CX3CR1 also localizes to microglia in the RN and hippocampus. Functionally, SDF-1a (10 nM) increases spontaneous inhibitory postsynaptic current (sIPSC) frequency and evoked IPSC (eIPSC) amplitude, while decreasing paired-pulse ratio (PPR) selectively in 5-HT neurons, thus stimulating presynaptic GABA release at these neurons. Alternatively, fractalkine (10 nM) increases sIPSC and eIPSC amplitude without changing PPR selectively in 5-HT neurons, thereby elevating the postsynaptic GABA receptor number or sensitivity. These results are dose-dependent and receptor-mediated. Chemokine interactions with serotonin, a neurotransmitter regulating mood, may lead to therapies for depression comorbid with immune diseases. Additional immunohistochemical analysis in the brain shows CXCR4 and CX3CR1 neuronal co-localization with the mu-opioid receptor (MOR) in the hippocampus, cingulate cortex, periaqueductal grey (PAG), nucleus accumbens, ventral tegmental area, globus pallidus, but not in the striatum or habenular nuclei, suggesting region specific receptor interactions. Electrophysiological recordings following morphine, SDF-1?? or fractalkine in vitro treatment reveal morphine (10 ?M)-mediated hyperpolarization of the membrane potential and reduction of the input resistance of PAG neurons, however, SDF-1??and fractalkine at 10 nM do not impact either parameter. In combination, SDF-1? inhibits morphine's actions in all PAG neurons tested, and fractalkine blocks morphine-mediated changes in 60% of PAG neurons examined. Thus, CXCR4 as well as CX3CR1, although less consistently, both appear to desensitize MOR at the neuronal level. Chemokine-opioid receptor interactions may mediate novel mechanisms to treat neuro-inflammatory pain and opiate abuse. The combined anatomical and electrophysiological results support chemokines as neuromodulatory proteins that may provide communication between the nervous and immune systems.

Temple University – Theses

Advisors/Committee Members: Kirby, Lynn, Adler, Martin W., Barbe, Mary F., Black, Mark M., Brailoiu, Eugen, Unterwald, Ellen M..

Subjects/Keywords: Biology, Anatomy; Biology, Neuroscience; Biology, Cell; Chemokines; Serotonin; Mu-opioid receptor; Co-localization; Electrophysiology; Heterologous desensitization

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

APA (6th Edition):

Heinisch, S. (2008). Chemokine interactions with the serotonin and opioid systems: anatomical and electrophysiological studies in the rat brain. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,9181

Chicago Manual of Style (16th Edition):

Heinisch, Silke. “Chemokine interactions with the serotonin and opioid systems: anatomical and electrophysiological studies in the rat brain.” 2008. Doctoral Dissertation, Temple University. Accessed October 27, 2020. http://digital.library.temple.edu/u?/p245801coll10,9181.

MLA Handbook (7th Edition):

Heinisch, Silke. “Chemokine interactions with the serotonin and opioid systems: anatomical and electrophysiological studies in the rat brain.” 2008. Web. 27 Oct 2020.

Vancouver:

Heinisch S. Chemokine interactions with the serotonin and opioid systems: anatomical and electrophysiological studies in the rat brain. [Internet] [Doctoral dissertation]. Temple University; 2008. [cited 2020 Oct 27]. Available from: http://digital.library.temple.edu/u?/p245801coll10,9181.

Council of Science Editors:

Heinisch S. Chemokine interactions with the serotonin and opioid systems: anatomical and electrophysiological studies in the rat brain. [Doctoral Dissertation]. Temple University; 2008. Available from: http://digital.library.temple.edu/u?/p245801coll10,9181

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