The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Janet R. Keast - One of the best experts on this subject based on the ideXlab platform.
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neurturin regulates postnatal differentiation of parasympathetic Pelvic Ganglion neurons initial axonal projections and maintenance of terminal fields in male urogenital organs
The Journal of Comparative Neurology, 2008Co-Authors: Hui Yan, Janet R. KeastAbstract:We have investigated the development of autonomic nerves in the urogenital tract of male mice and the effect of neurturin gene deletion on this process. At birth, autonomic innervation of the reproductive organs was sparse, but urinary bladder smooth muscle was well innervated. Further innervation of reproductive tissues occurred until P21, but noradrenergic axons established their complete terminal field later than nitrergic cholinergic axons: in adults the former are more prevalent, yet this became apparent only at P7 (vas deferens, seminal vesicles), P14 (prostate) or after P14 (penis). Neurturin was essential for initial projection of axons (mucosa of vas deferens), maintenance of terminal fields (prostate and seminal vesicles), or both functions (cavernosum of penis). In contrast, some targets (e.g., bladder muscle and suburothelium, vas deferens smooth muscle) were unaffected by neurturin gene deletion. Pelvic Ganglion neurons more than doubled between birth and adulthood, probably as aresult of continued maturation of p75-positive undifferentiated neuronal precursors rather than cell division. The adult number of neurons was achieved by P7 (sympathetic) or P21 (parasympathetic). In adult neurturin knockout mice, there were ∼25% fewer parasympathetic neurons compared with wild types, because of failure of differentiation after P14. This study revealed the complexity of postnatal maturation of urogenital innervation, with each organ showing a distinct chronology of innervation and different requirement for neurturin. Our results also indicate that in adults there will be distinct differences in neurturin dependence between organs, such that proregenerative therapies may have to be tailored specifically for the nerve pathway of interest. J. Comp. Neurol. 507:1169–1183, 2008. © 2008 Wiley-Liss, Inc.
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Testosterone and nerve growth factor have distinct but interacting effects on structure and neurotransmitter expression of adult Pelvic Ganglion cells in vitro
Neuroscience, 2001Co-Authors: S.m Meusburger, Janet R. KeastAbstract:Circulating testosterone has potent effects on the structure and function of many Pelvic Ganglion cells in adult rats in vivo. However not all androgen-sensitive Pelvic neurones possess androgen receptors and testosterone effects may therefore be indirect, by an action on the target organs. Here we have examined if testosterone influences neuronal structure in vitro in Pelvic Ganglion cells cultured from adult male rats. We have also used multiple label immunofluorescence to monitor the expression of transmitter-synthesising enzymes and peptides under various culture conditions. Testosterone was a more potent stimulant of noradrenergic soma growth in culture than nerve growth factor. Whereas nerve growth factor increased the number, branching and length of neurites, testosterone stimulated growth of a small number of very short processes, each of which bore numerous short protrusions. Testosterone also impeded the longer neurite growth induced by nerve growth factor. Many Pelvic Ganglion cells altered their expression of transmitters/neuropeptides under different culture conditions. In particular, under control conditions or during nerve growth factor treatment, vasoactive intestinal peptide was up-regulated in noradrenergic and cholinergic neurones; testosterone impeded this up-regulation in noradrenergic neurones. Choline acetyltransferase immunoreactivity could only be visualised when nerve growth factor was present in the cultures, and cholinergic neurones showed less neurite outgrowth than noradrenergic neurones under all culture conditions. Nerve growth factor did not stimulate levels of this enzyme as strongly if testosterone was present. This study has shown that testosterone has potent effects on the structure of many Pelvic Ganglion cells in vitro. It is possible that these effects are mediated indirectly, e.g. by stimulating glial-derived substances, however our results suggest that the effects are not mediated by nerve growth factor. The results also show that testosterone influences some of the actions of nerve growth factor, suggesting that there may be complex interactions between steroid signalling and neurotrophic factors in maintaining neuronal structure and function in vivo.
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transmitter profile and spinal inputs of Pelvic Ganglion cells projecting with preGanglionic axons along the hypogastric and Pelvic nerves of the male rat
Neuroscience Letters, 2000Co-Authors: Mark E Kepper, Janet R. KeastAbstract:Pelvic autonomic Ganglion cells receive spinal preGanglionic inputs via the hypogastric (lumbar) or Pelvic (sacral) nerves. Damage to these nerves stimulates axogenesis (sprouting) from Pelvic Ganglion cells and two possible triggers are deafferentation (decentralisation) or, if some Ganglion cells project centrally in these nerves, axotomy. We have used a combination of retrograde tracing and immunohistochemistry in male rats to identify the number of Pelvic Ganglion cells that project centrally along these nerves, their transmitter type and the spinal level of their preGanglionic inputs. Only a small number (<1%) of Pelvic Ganglion cells project along these nerves; 29-65 project in each hypogastric nerve and 41-71 in each Pelvic nerve. These neurons comprise of both cholinergic and noradrenergic classes and the majority receive preGanglionic inputs from the nerve in which they also project. These results suggest that damage of the hypogastric and Pelvic nerves close to the Pelvic Ganglion is unlikely to cause axotomy of many Pelvic Ganglion cells. Therefore deafferentation rather than axotomy is likely to be the primary trigger of axogenesis occurring in Pelvic ganglia after these lesions.
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Transmitter profile and spinal inputs of Pelvic Ganglion cells projecting with preGanglionic axons along the hypogastric and Pelvic nerves of the male rat.
Neuroscience letters, 2000Co-Authors: Mark E Kepper, Janet R. KeastAbstract:Pelvic autonomic Ganglion cells receive spinal preGanglionic inputs via the hypogastric (lumbar) or Pelvic (sacral) nerves. Damage to these nerves stimulates axogenesis (sprouting) from Pelvic Ganglion cells and two possible triggers are deafferentation (decentralisation) or, if some Ganglion cells project centrally in these nerves, axotomy. We have used a combination of retrograde tracing and immunohistochemistry in male rats to identify the number of Pelvic Ganglion cells that project centrally along these nerves, their transmitter type and the spinal level of their preGanglionic inputs. Only a small number (
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Androgen-sensitive preGanglionic neurons innervate the male rat Pelvic Ganglion.
Neuroscience, 1999Co-Authors: T.w. Watkins, Janet R. KeastAbstract:In adult male rats many Pelvic autonomic Ganglion cells change in structure and function after androgen deprivation. In this study we have investigated whether preGanglionic neurons in the lumbar and sacral spinal cord that innervate these Ganglion cells are also androgen-sensitive. Numerous spinal neurons retrogradely labelled from the Pelvic Ganglion possessed androgen receptor immunoreactivity and this was diminished by castration or enhanced by additional testosterone exposure. These comprised 27-77% of all preGanglionic neurons innervating the Pelvic Ganglion, depending on the spinal level and whether animals were administered testosterone prior to sacrifice or not. When adult animals were castrated, no change occurred in the soma size or number of primary dendrites in these lumbar or sacral preGanglionic neurons. Mean dendrite length was also determined in lumbar preGanglionic neurons supplying the Pelvic Ganglion, but was not affected by castration. However, the total volume of lumbar preGanglionic terminal varicosities supplying each noradrenergic Pelvic Ganglion cell decreased in parallel with the volume of the target neuron. These studies show that many preGanglionic autonomic neurons involved in Pelvic reflexes are androgen-sensitive, but that androgens selectively influence particular neuronal compartments. The prevalence of androgen receptors in these neurons suggests that testosterone may directly influence gene expression of preGanglionic neurons. Together these studies suggest that testosterone (or a metabolite) has widespread actions on Pelvic reflex circuits during adulthood and that under conditions of diminished circulating androgens a variety of reflex activities may not function optimally.
Tom F. Lue - One of the best experts on this subject based on the ideXlab platform.
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expression of a distinct set of chemokine receptors in adipose tissue derived stem cells is responsible for in vitro migration toward chemokines appearing in the major Pelvic Ganglion following cavernous nerve injury
Sexual Medicine, 2013Co-Authors: Maarten Albersen, Tom F. Lue, Petter Hedlund, Trinity J. Bivalacqua, Chingshwun Lin, Joost Berkers, Philip Dekoninck, Jan Deprest, Hendrik Van Poppel, Dirk De RidderAbstract:Abstract Introduction Adipose tissue‐derived stem cells (ADSCs) herald tremendous promise for clinical application in a wide range of injuries and diseases. Several preclinical reports demonstrate their efficacy in the treatment of cavernous nerve (CN) injury‐induced erectile dysfunction in rats. It was recently illustrated that these effects were established as a result of ADSC migration to the major Pelvic Ganglion (MPG) where these cells induced neuroregeneration in loco. Aims The study aims to identify chemotactic factors in the MPG following injury and to match upregulated chemokines to their respective receptors in human ADSC on the genomic, structural, and functional levels. Methods Quantitative real‐time polymerase chain reaction, fluorescence‐activated cell sorting (FACS), intracellular FACS, immunofluorescence microscopy, migration assays, and calcium imaging were used in this study. Main Outcome Measures The main outcomes are chemokine expression in the MPG following CN injury, and the functional and structural presence of chemokine receptors in ADSC. Results CCR4, CX3CR1, and XCR1 are functionally and structurally present in human ADSC, and are activated by the chemokines CCL2, CX3CL1, and XCL1 respectively, which are upregulated in the MPG following CN injury. CXCR4 and its ligand CXCL12 (SDF1) are likely no major homing factors for ADSC. Expression of chemokine receptor mRNA in ADSC did not necessarily translate into receptor presence at the cell surface and/or functional activation of these receptors. Most of the expressed chemokine receptors were detected in the intracellular compartment of these cells. Conclusions We identified the ligand/chemokine receptor pairs CCL2/CCR4, CX3CL1/CX3CR1, and XCL1/XCR1 as potentially responsible for ADSC homing toward the MPG following CN injury. The intracellular localization of various chemokine receptors likely indicates redirecting of chemokine receptors to the cell surface under specific cellular conditions. Furthermore, modification of expression of these receptors at the genomic level may potentially lead to improved migration toward injury sites and thus enhancement of treatment efficacy. Albersen M, Berkers J, Dekoninck P, Deprest J, Lue TF, Hedlund P, Lin C‐S, Bivalacqua TJ, Van Poppel H, De Ridder D, and Van der Aa F. Expression of a distinct set of chemokine receptors in adipose tissue‐derived stem cells is responsible for in vitro migration toward chemokines appearing in the major Pelvic Ganglion following cavernous nerve injury. Sex Med 2013;1:3–15.
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Expression of a Distinct Set of Chemokine Receptors in Adipose Tissue‐Derived Stem Cells is Responsible for In Vitro Migration Toward Chemokines Appearing in the Major Pelvic Ganglion Following Cavernous Nerve Injury
Sexual medicine, 2013Co-Authors: Maarten Albersen, Tom F. Lue, Petter Hedlund, Trinity J. Bivalacqua, Chingshwun Lin, Joost Berkers, Philip Dekoninck, Jan Deprest, Hendrik Van Poppel, Dirk De RidderAbstract:Abstract Introduction Adipose tissue‐derived stem cells (ADSCs) herald tremendous promise for clinical application in a wide range of injuries and diseases. Several preclinical reports demonstrate their efficacy in the treatment of cavernous nerve (CN) injury‐induced erectile dysfunction in rats. It was recently illustrated that these effects were established as a result of ADSC migration to the major Pelvic Ganglion (MPG) where these cells induced neuroregeneration in loco. Aims The study aims to identify chemotactic factors in the MPG following injury and to match upregulated chemokines to their respective receptors in human ADSC on the genomic, structural, and functional levels. Methods Quantitative real‐time polymerase chain reaction, fluorescence‐activated cell sorting (FACS), intracellular FACS, immunofluorescence microscopy, migration assays, and calcium imaging were used in this study. Main Outcome Measures The main outcomes are chemokine expression in the MPG following CN injury, and the functional and structural presence of chemokine receptors in ADSC. Results CCR4, CX3CR1, and XCR1 are functionally and structurally present in human ADSC, and are activated by the chemokines CCL2, CX3CL1, and XCL1 respectively, which are upregulated in the MPG following CN injury. CXCR4 and its ligand CXCL12 (SDF1) are likely no major homing factors for ADSC. Expression of chemokine receptor mRNA in ADSC did not necessarily translate into receptor presence at the cell surface and/or functional activation of these receptors. Most of the expressed chemokine receptors were detected in the intracellular compartment of these cells. Conclusions We identified the ligand/chemokine receptor pairs CCL2/CCR4, CX3CL1/CX3CR1, and XCL1/XCR1 as potentially responsible for ADSC homing toward the MPG following CN injury. The intracellular localization of various chemokine receptors likely indicates redirecting of chemokine receptors to the cell surface under specific cellular conditions. Furthermore, modification of expression of these receptors at the genomic level may potentially lead to improved migration toward injury sites and thus enhancement of treatment efficacy. Albersen M, Berkers J, Dekoninck P, Deprest J, Lue TF, Hedlund P, Lin C‐S, Bivalacqua TJ, Van Poppel H, De Ridder D, and Van der Aa F. Expression of a distinct set of chemokine receptors in adipose tissue‐derived stem cells is responsible for in vitro migration toward chemokines appearing in the major Pelvic Ganglion following cavernous nerve injury. Sex Med 2013;1:3–15.
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upregulation of penile brain derived neurotrophic factor bdnf and activation of the jak stat signalling pathway in the major Pelvic Ganglion of the rat after cavernous nerve transection
European Urology, 2007Co-Authors: Anthony J Bella, Guiting Lin, Maurice M Garcia, Kavirach Tantiwongse, William O Brant, Chingshwun Lin, Tom F. LueAbstract:Abstract Objectives Increasing attention is being focused on identifying novel approaches to recover cavernous nerve (CN) function after injury or secondary to disease states such as diabetes mellitus. We examined penile brain-derived neurotrophic factor (BDNF) and neurotrophin-3 ( NT-3 ) expression, and activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) molecular pathway in the major Pelvic Ganglion (MPG) after CN injury in the rat. Methods Five groups of eight male Sprague-Dawley rats (4 mo, 250–300g) were used in this study. The penis and MPG with attached CN segment were harvested at 0h (controls), 12, and 24h, as well as at 5 and 12 d after CN axotomy, for protein, messenger RNA (mRNA), and immunohistochemical analysis. Results mRNA and protein expression of BDNF was upregulated in the penis after injury ( p p Conclusions This study demonstrates increased expression of penile BDNF and upregulation of phosphorylated STAT1 and STAT3 in the MPG in response to CN transection. Activation of the JAK/STAT pathway after injury represents a promising new molecular target for modulating CN survival and regeneration.
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Upregulation of penile brain-derived neurotrophic factor (BDNF) and activation of the JAK/STAT signalling pathway in the major Pelvic Ganglion of the rat after cavernous nerve transection.
European urology, 2006Co-Authors: Anthony J Bella, Guiting Lin, Maurice M Garcia, Kavirach Tantiwongse, William O Brant, Chingshwun Lin, Tom F. LueAbstract:Abstract Objectives Increasing attention is being focused on identifying novel approaches to recover cavernous nerve (CN) function after injury or secondary to disease states such as diabetes mellitus. We examined penile brain-derived neurotrophic factor (BDNF) and neurotrophin-3 ( NT-3 ) expression, and activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) molecular pathway in the major Pelvic Ganglion (MPG) after CN injury in the rat. Methods Five groups of eight male Sprague-Dawley rats (4 mo, 250–300g) were used in this study. The penis and MPG with attached CN segment were harvested at 0h (controls), 12, and 24h, as well as at 5 and 12 d after CN axotomy, for protein, messenger RNA (mRNA), and immunohistochemical analysis. Results mRNA and protein expression of BDNF was upregulated in the penis after injury ( p p Conclusions This study demonstrates increased expression of penile BDNF and upregulation of phosphorylated STAT1 and STAT3 in the MPG in response to CN transection. Activation of the JAK/STAT pathway after injury represents a promising new molecular target for modulating CN survival and regeneration.
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brain derived neurotrophic factor bdnf acts primarily via the jak stat pathway to promote neurite growth in the major Pelvic Ganglion of the rat part 2
The Journal of Sexual Medicine, 2006Co-Authors: Guiting Lin, Tom F. Lue, Anthony J Bella, Chingshwun LinAbstract:ABSTRACT Introduction Identification of the molecular mechanism of cavernous nerve regeneration is essential for future development of neuroprotective and regenerative strategies. Aim To identify specific signal transduction pathway(s) associated with brain‐derived neurotrophic factor (BDNF) enhanced cavernous nerve regeneration in an in vitro model. Materials and Methods Using 6‐month‐old male Fisher rats, inhibitors of four candidate signaling pathways were added to BDNF‐treated explant cultures of major Pelvic ganglia with attached cavernous nerve fragments. Study groups comprised of controls, BDNF alone at 50 ng/mL, or BDNF 50 ng/mL and inhibitors against MEK, PI3‐K, PKA, and JAK/STAT pathways at increasing concentrations. Main Outcome Measure The maximal neurite length for each tissue culture was measured and the mean maximal length ± standard deviation was determined for all groups at 24, 36, and 48 hours. Results The JAK/STAT specific inhibitor AG490 significantly reduced BDNF‐enhanced neurite growth. Maximum neurite lengths at 24, 36, and 48 hours for BDNF 50 ng/mL treated groups were 182.3, 348.1, and 528.1 µm, compared with AG490 at 25 µM (86.4, 165.1, 278.3 µm), 50 µM (78.8, 151.7, 235.3 µm), and 100 µM (71.83, 107.0, 219.6 µm) ( P P Conclusion The JAK/STAT pathway is the major signal‐transduction pathway of BDNF‐enhanced cavernous nerve growth in an in vitro rat model. Bella AJ, Lin G, Tantiwongse K, Garcia M, Lin C‐S, Brant W, and Lue TF. Brain‐derived neurotrophic factor (BDNF) acts primarily via the JAK/STAT pathway to promote neurite growth in the major Pelvic Ganglion of the rat: Part I. J Sex Med 2006;3:815–820.
Seong Woo Jeong - One of the best experts on this subject based on the ideXlab platform.
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Neuregulin 1 as an endogenous regulator of nicotinic acetylcholine receptors in adult major Pelvic Ganglion neurons.
Biochemical and biophysical research communications, 2015Co-Authors: Han-gyu Kim, Sung-min Cho, Choong-ku Lee, Seong Woo JeongAbstract:We investigated whether endogenous neuregulin 1 (NRG1) is released in a soluble form (called sNRG1) and upregulates expression of nicotinic acetylcholine receptor (nAChR) in autonomic major Pelvic Ganglion (MPG) neurons of adult rats. To elicit the release of sNRG1, either the hypogastric nerve or the Pelvic nerve was electrically stimulated. Then, the MPG-conditioned medium (CM) was subjected to western blotting using an antibody directed against the N-terminal ectodomain of NRG1. Both sympathetic and parasympathetic nerve activation elicited the release of sNRG1 from MPG neurons in a frequency-dependent manner. The sNRG1 release was also induced by treatment of MPG neurons with either high KCl or neurotrophic factors. The biological activity of the released sNRG1 was detected by tyrosine phosphorylation (p185) of the ErbB2 receptors in MPG neurons. When MPG neurons were incubated for 6 h in the CM, the protein level of the nAChR α3 subunit and ACh-induced current (IACh) density were significantly increased. The CM-induced changes in IACh was abolished by a selective ErbB2 tyrosine kinase inhibitor. Taken together, these data suggest that NRG1 functions as an endogenous regulator of nAChR expression in adult MPG neurons.
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bladder outlet obstruction causes up regulation of nicotinic acetylcholine receptors in bladder projecting Pelvic Ganglion neurons
Brain Research, 2015Co-Authors: Hyun Chul Chung, Choong-ku Lee, Kwang Hwa Park, Seong Woo JeongAbstract:Pelvic Ganglion (PG) neurons relay sympathetic and parasympathetic signals to the lower urinary tract, comprising the urinary bladder and bladder outlet, and are thus essential for both storage and voiding reflexes. Autonomic transmission is mediated by activation of the nicotinic acetylcholine receptor (nAChR) in PG neurons. Previously, bladder outlet obstruction (BOO), secondary to benign prostatic hyperplasia, was found to increase soma sizes of bladder-projecting PG neurons. To date, however, it remains unknown whether these morphological changes are accompanied by functional plasticity in PG neurons. In the present study, we investigated whether BOO alters acetylcholine receptor (nAChR) transcript expression and current density in bladder PG neurons. Partial ligation of the rat urethra for six weeks induced detrusor overactivity (DO), as observed during cystometrical measurement. In rats exhibiting DO, membrane capacitance of parasympathetic bladder PG neurons was selectively increased. Real-time PCR analysis revealed that BOO enhanced the expression of the transcripts encoding the nAChR α3 and β4 subunits in PG neurons. Notably, BOO significantly increased ACh-evoked current density in parasympathetic bladder PG neurons, whereas no changes were observed in sympathetic bladder and parasympathetic penile PG neurons. In addition, other ligand-gated ionic currents were immune to BOO in bladder PG neurons. Taken together, these data suggest that BOO causes upregulation of nAChR in parasympathetic bladder PG neurons, which in turn may potentiate Ganglionic transmission and contribute to the development of DO.
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afterhyperpolarization induced by the activation of nicotinic acetylcholine receptors in Pelvic Ganglion neurons of male rats
Neuroscience Letters, 2010Co-Authors: Kyu Sang Park, Seong Woo Jeong, Seung Kuy Cha, Min Jeong Kim, Na Hyun Kim, Joong Woo Lee, In Deok KongAbstract:Abstract The electrophysiological mechanism underlying afterhyperpolarization induced by the activation of the nicotinic acetylcholine receptor (nAChR) in male rat major Pelvic Ganglion neurons (MPG) was investigated using a gramicidin-perforated patch clamp and microscopic fluorescence measurement system. Acetylcholine (ACh) induced fast depolarization through the activation of nAChR, followed by a sustained hyperpolarization after the removal of ACh in a dose-dependent manner (10 μM to 1 mM). ACh increased both intracellular Ca2+ ([Ca2+]i) and Na+ concentrations ([Na+]i) in MPG neurons. The recovery of [Na+]i after the removal of ACh was markedly delayed by ouabain (100 μM), an inhibitor of Na+/K+ ATPase. Pretreatment with ouabain blocked ACh-induced hyperpolarization by 67.2 ± 5.4% (n = 7). ACh-induced hyperpolarization was partially attenuated by either the chelation of [Ca2+]i with BAPTA/AM (20 μM) or the blockade of small-conductance Ca2+-activated K+ channels by apamin (500 nM). Taken together, the activation of nAChR increases [Na+]i and [Ca2+]i, which activates Na+/K+ ATPase and Ca2+-activated K+ channels, respectively. Consequently, hyperpolarization occurs after the activation of nAChR in the autonomic Pelvic ganglia.
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Expression of GABAA receptor β2/3 subunits in the rat major Pelvic Ganglion
Neuroscience Letters, 2006Co-Authors: Jung Cheol Park, Dae Yong Song, Jin Suk Lee, In Deok Kong, Seong Woo Jeong, Bonghee Lee, Ho Suck Kang, Byung Pil ChoAbstract:Several pharmacological and physiological studies have suggested that GABA(A) receptors (GABA(A) Rs) may exist in the rat major Pelvic Ganglion (MPG), a large coalescent Pelvic Ganglion that contains both sympathetic and parasympathetic components which innervates Pelvic organs. However, the presence of GABA(A) R in the MPG has never been demonstrated directly by morphological studies. In the present study, we used immunohistochemistry to demonstrate the existence of GABA(A) R beta2/3 subunits for the first time in the rat MPG. We also analyzed the neurochemical properties of MPG neurons expressing GABA(A) R beta2/3 subunits. GABA(A) R beta2/3-immunoreactive (-IR) neurons occupied 27.4+/-7.0% of the whole neuronal population, and many of these (77.6%) were co-localized with tyrosine hydroxylase (TH). Likewise, most (86.5%) of TH-IR neurons were GABA(A) R beta2/3-positive. GABA(A) R beta2/3 subunits were also expressed in a few VIP- or NOS-IR neurons, the cholinergic or non-adrenergic, non-cholinergic (NANC) neurons. These results suggest that GABA(A) Rs are involved in the modulation of most sympathetic, noradrenergic neurons and also a subset of VIP and NOS neurons of the rat MPG.
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Expression of GABAA receptor beta2/3 subunits in the rat major Pelvic Ganglion.
Neuroscience letters, 2006Co-Authors: Jung Cheol Park, Dae Yong Song, Jin Suk Lee, In Deok Kong, Seong Woo Jeong, Bonghee Lee, Ho Suck Kang, Byung Pil ChoAbstract:Several pharmacological and physiological studies have suggested that GABA(A) receptors (GABA(A) Rs) may exist in the rat major Pelvic Ganglion (MPG), a large coalescent Pelvic Ganglion that contains both sympathetic and parasympathetic components which innervates Pelvic organs. However, the presence of GABA(A) R in the MPG has never been demonstrated directly by morphological studies. In the present study, we used immunohistochemistry to demonstrate the existence of GABA(A) R beta2/3 subunits for the first time in the rat MPG. We also analyzed the neurochemical properties of MPG neurons expressing GABA(A) R beta2/3 subunits. GABA(A) R beta2/3-immunoreactive (-IR) neurons occupied 27.4+/-7.0% of the whole neuronal population, and many of these (77.6%) were co-localized with tyrosine hydroxylase (TH). Likewise, most (86.5%) of TH-IR neurons were GABA(A) R beta2/3-positive. GABA(A) R beta2/3 subunits were also expressed in a few VIP- or NOS-IR neurons, the cholinergic or non-adrenergic, non-cholinergic (NANC) neurons. These results suggest that GABA(A) Rs are involved in the modulation of most sympathetic, noradrenergic neurons and also a subset of VIP and NOS neurons of the rat MPG.
J. P. Rousseau - One of the best experts on this subject based on the ideXlab platform.
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localization of androgen receptor in nitric oxide synthase and vasoactive intestinal peptide containing neurons of the major Pelvic Ganglion innervating the rat penis
Journal of Neuroendocrinology, 2003Co-Authors: A. Schirar, Chawnshang Chang, J. P. RousseauAbstract:Neurons of the rat major Pelvic ganglia provide innervation to the Pelvic organs and external genitalia. In these ganglia, a subpopulation of neurons containing either nitric oxide synthase or vasoactive intestinal peptide or both molecules, is involved in penile erection. The androgen dependence of penile erection is a well established fact. After castration, decreased testosterone levels have been documented to produce erectile dysfunction possibly resulting from functional alterations in major Pelvic Ganglion neurons. It was therefore of interest to investigate the presence of androgen receptor within these Ganglionic neurons. By using immunohistochemistry and a retrograde labeling technique we have demonstrated that the androgen receptor is present in about 40% of neurons of the major Pelvic Ganglion innervating the corpora cavernosa of the rat penis. In the major Pelvic Ganglion, 87% and 81% of the neurons labeled with the fluorescent dye Fast Blue from the penis contained nitric oxide synthase-like immunoreactivity and vasoactive intestinal peptide-like immunoreactivity, respectively. Androgen receptor was present in 20% of neurons containing vasoactive intestinal peptide-like immunoreactivity and about 40% of those containing nitric oxide synthase-like immunoreactivity. These results suggest that androgens, which are known to modulate penile erection, may regulate nitric oxide synthase and vasoactive intestinal peptide within the major Pelvic Ganglion via a direct interaction with Ganglionic neurons.
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Localization of Androgen Receptor in Nitric Oxide Synthase‐ and Vasoactive Intestinal Peptide‐Containing Neurons of the Major Pelvic Ganglion Innervating the Rat Penis
Journal of neuroendocrinology, 1997Co-Authors: A. Schirar, Chawnshang Chang, J. P. RousseauAbstract:Neurons of the rat major Pelvic ganglia provide innervation to the Pelvic organs and external genitalia. In these ganglia, a subpopulation of neurons containing either nitric oxide synthase or vasoactive intestinal peptide or both molecules, is involved in penile erection. The androgen dependence of penile erection is a well established fact. After castration, decreased testosterone levels have been documented to produce erectile dysfunction possibly resulting from functional alterations in major Pelvic Ganglion neurons. It was therefore of interest to investigate the presence of androgen receptor within these Ganglionic neurons. By using immunohistochemistry and a retrograde labeling technique we have demonstrated that the androgen receptor is present in about 40% of neurons of the major Pelvic Ganglion innervating the corpora cavernosa of the rat penis. In the major Pelvic Ganglion, 87% and 81% of the neurons labeled with the fluorescent dye Fast Blue from the penis contained nitric oxide synthase-like immunoreactivity and vasoactive intestinal peptide-like immunoreactivity, respectively. Androgen receptor was present in 20% of neurons containing vasoactive intestinal peptide-like immunoreactivity and about 40% of those containing nitric oxide synthase-like immunoreactivity. These results suggest that androgens, which are known to modulate penile erection, may regulate nitric oxide synthase and vasoactive intestinal peptide within the major Pelvic Ganglion via a direct interaction with Ganglionic neurons.
In Deok Kong - One of the best experts on this subject based on the ideXlab platform.
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afterhyperpolarization induced by the activation of nicotinic acetylcholine receptors in Pelvic Ganglion neurons of male rats
Neuroscience Letters, 2010Co-Authors: Kyu Sang Park, Seong Woo Jeong, Seung Kuy Cha, Min Jeong Kim, Na Hyun Kim, Joong Woo Lee, In Deok KongAbstract:Abstract The electrophysiological mechanism underlying afterhyperpolarization induced by the activation of the nicotinic acetylcholine receptor (nAChR) in male rat major Pelvic Ganglion neurons (MPG) was investigated using a gramicidin-perforated patch clamp and microscopic fluorescence measurement system. Acetylcholine (ACh) induced fast depolarization through the activation of nAChR, followed by a sustained hyperpolarization after the removal of ACh in a dose-dependent manner (10 μM to 1 mM). ACh increased both intracellular Ca2+ ([Ca2+]i) and Na+ concentrations ([Na+]i) in MPG neurons. The recovery of [Na+]i after the removal of ACh was markedly delayed by ouabain (100 μM), an inhibitor of Na+/K+ ATPase. Pretreatment with ouabain blocked ACh-induced hyperpolarization by 67.2 ± 5.4% (n = 7). ACh-induced hyperpolarization was partially attenuated by either the chelation of [Ca2+]i with BAPTA/AM (20 μM) or the blockade of small-conductance Ca2+-activated K+ channels by apamin (500 nM). Taken together, the activation of nAChR increases [Na+]i and [Ca2+]i, which activates Na+/K+ ATPase and Ca2+-activated K+ channels, respectively. Consequently, hyperpolarization occurs after the activation of nAChR in the autonomic Pelvic ganglia.
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modulation of gaba a receptor by protein kinase c in autonomic major Pelvic Ganglion neurons
대한의생명과학회지, 2008Co-Authors: Yeun Jong Choi, Daeran Kim, Seungkyu Cha, In Deok KongAbstract:γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system, and its actions are mediated by subtypes of GABA receptors named as GABA A , GABA B , and GABA C . GABA A , receptor consisting of α, β, γ and δ subunits is a heterooligomeric ligand-gated chloride channel. This study was performed to investigate regulation of GABA A receptor by protein kinase C (PKC). Ion currents were recorded using gramicidine-perforated patch and whole cell patch clamp. mRNA encoding the subunits of PKC expressed in major Pelvic Ganglion (MPG) neurons was detected by using RT-PCR. The GABA-induced inward current was increased by PKC activators and decreased by PKC inhibitors, respectively. These effects were not associated with intracellular Ca²? and OAG (1-oleoyl-2-acetyl-sn-glycerol), a membrane permeable diacylglycerol (DAG) analogue. These results mean that the subfamily of PKC participating in activation of GABA A receptor would be an atypical PKC (aPKC). Among theses, ξ isoform of aPKC was detected by RT-PCR. Taking together, we suggest that excitable GABA A receptor in sympathetic MPG neuron seemed to be regulated by aPKC, particular in ξ isoform. The regulatory roles of PKC on excitatory GABA A receptors in sympathetic neurons of MPG may be an important factor to control the functional activity of various Pelvic organs such as bowel movement, micturition and erection.
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regulation of nicotinic acetylcholine receptor by tyrosine kinase in autonomic major Pelvic Ganglion neurons
대한의생명과학회지, 2007Co-Authors: Daeran Kim, Kyu Sang Park, Sung Wan Ahn, In Deok KongAbstract:It is widely known that protein tyrosine kinases (PTKs) are involved in controlling many biological processes such as cell growth, differentiation, proliferation, survival and apoptosis. An α3β4 subunit combination acts as a major functional acetylcholine receptor (nAChRs) in male rat major Pelvic Ganglion (MPG) neurons, and their activation induces fast inward currents and intracellular calcium increases. Recently it has been reported that the activity of acetylcholine receptors (AChRs) in some neurons can be negatively regulated by PTKs. However, the exact mechanism of regulation of nAChRs by PTKs is poorly understood. Therefore, we examined the potential role particular in nAChR by PTK using electrophysiology and calcium imaging in male rat MPG neurons. ACh induced inward currents and (Ca²?) i increases in MPG neurons, concomitantly. These responses were inhibited by more than 90% in Na?- or Ca²?- free solution. α-conotoxin AuIB, a selective α3β4 nAChR blocker, inhibited ACh-induced inward currents. Genistein (10 μM), a broad-spectrum tyrosine kinase inhibitor, markedly decreased ACh-induced currents and Ca²? transients, whereas 10 μM genistin, an inactive analogue, had little effect. Overall these data suggest that the activities of α3β4 AChRs in MPG neurons are positively regulated by PTK. In conclusion, tyrosine kinase may be one of the key factors in the regulation of α3β4 nAChRs in rat MPG neurons, which may play an important roles in the autonomic neuronal function such as synaptic transmission, autonomic reflex, and neuronal plasticity.
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Expression of GABAA receptor β2/3 subunits in the rat major Pelvic Ganglion
Neuroscience Letters, 2006Co-Authors: Jung Cheol Park, Dae Yong Song, Jin Suk Lee, In Deok Kong, Seong Woo Jeong, Bonghee Lee, Ho Suck Kang, Byung Pil ChoAbstract:Several pharmacological and physiological studies have suggested that GABA(A) receptors (GABA(A) Rs) may exist in the rat major Pelvic Ganglion (MPG), a large coalescent Pelvic Ganglion that contains both sympathetic and parasympathetic components which innervates Pelvic organs. However, the presence of GABA(A) R in the MPG has never been demonstrated directly by morphological studies. In the present study, we used immunohistochemistry to demonstrate the existence of GABA(A) R beta2/3 subunits for the first time in the rat MPG. We also analyzed the neurochemical properties of MPG neurons expressing GABA(A) R beta2/3 subunits. GABA(A) R beta2/3-immunoreactive (-IR) neurons occupied 27.4+/-7.0% of the whole neuronal population, and many of these (77.6%) were co-localized with tyrosine hydroxylase (TH). Likewise, most (86.5%) of TH-IR neurons were GABA(A) R beta2/3-positive. GABA(A) R beta2/3 subunits were also expressed in a few VIP- or NOS-IR neurons, the cholinergic or non-adrenergic, non-cholinergic (NANC) neurons. These results suggest that GABA(A) Rs are involved in the modulation of most sympathetic, noradrenergic neurons and also a subset of VIP and NOS neurons of the rat MPG.
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Expression of GABAA receptor beta2/3 subunits in the rat major Pelvic Ganglion.
Neuroscience letters, 2006Co-Authors: Jung Cheol Park, Dae Yong Song, Jin Suk Lee, In Deok Kong, Seong Woo Jeong, Bonghee Lee, Ho Suck Kang, Byung Pil ChoAbstract:Several pharmacological and physiological studies have suggested that GABA(A) receptors (GABA(A) Rs) may exist in the rat major Pelvic Ganglion (MPG), a large coalescent Pelvic Ganglion that contains both sympathetic and parasympathetic components which innervates Pelvic organs. However, the presence of GABA(A) R in the MPG has never been demonstrated directly by morphological studies. In the present study, we used immunohistochemistry to demonstrate the existence of GABA(A) R beta2/3 subunits for the first time in the rat MPG. We also analyzed the neurochemical properties of MPG neurons expressing GABA(A) R beta2/3 subunits. GABA(A) R beta2/3-immunoreactive (-IR) neurons occupied 27.4+/-7.0% of the whole neuronal population, and many of these (77.6%) were co-localized with tyrosine hydroxylase (TH). Likewise, most (86.5%) of TH-IR neurons were GABA(A) R beta2/3-positive. GABA(A) R beta2/3 subunits were also expressed in a few VIP- or NOS-IR neurons, the cholinergic or non-adrenergic, non-cholinergic (NANC) neurons. These results suggest that GABA(A) Rs are involved in the modulation of most sympathetic, noradrenergic neurons and also a subset of VIP and NOS neurons of the rat MPG.