Hypogastric Ganglion Research Articles

Vesicoureteral Reflux in Children: Endoscopic Treatment

Endoscopic correction of vesicoureteral reflux in children has been increasingly used in the last years with encouraging results. During a 4-year period 152 children were treated by endoscopic injection of Teflon. A follow-up, ranging from 3 months to 5 years, was available for 173 refluxing ureters. For primary reflux, correction was observed after a single injection in 87% of the cases and in 93% after a second injection in some failures. In duplication, the technique is somewhat more difficult but the results quite satisfactory with 58% success after one injection, increasing to 74% after a second injection. The limitations of these techniques are underlined, the major concern being the safety of the injectable Teflon particles, eliciting a foreign-body granulomatous reaction with the potential hazard of distant migration. So far no long-term morbidity and complications have been observed with the use of Teflon to correct reflux. Extensive pathological study in 7 children submitted to ureteral reimplantation for failure of endoscopic correction showed a typical encapsulated granulomatous reaction below the intramural ureter, but particles of Teflon were noted in only one hypogastric ganglion when the Teflon was injected outside of the bladder. There is a need for finding an ideal substance for endoscopic injection, preferably prepared from the patient's own tissue allowing simple and safe correction of vesicoureteral reflux in children.

Inhibition of potassium currents by the sigma receptor ligand (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine in sympathetic neurons of the mouse isolated hypogastric ganglion

The actions of (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)3-PPP] on sympathetic neurons of the mouse isolated hypogastric ganglion were studied using the current clamp and single electrode voltage clamp techniques. In neurons studied under current clamp (+)3-PPP ( 10 −5 to 3 × 10 −4 M ) evoked a concentration-dependent depolarization, which was fully reversible on washout of the drug. The depolarization was associated with an increase in membrane input resistance. At membrane potentials between −43 and −65mV the amplitude of the depolarization was inversely related to the membrane potential. (+)3-PPP had no effect on membrane potential at potentials negative to −65mV. The effect of (+)3-PPP on the M-current was studied in cells voltage clamped at −40 mV and stepped to −60 mV for 300–500 ms. The slow current relaxations seen during and after the voltage step are largely due to the M-current. (+)3-PPP ( 3 × 10 −5 to 3 × 10 −4M ) inhibited the M-current and produced an inward current in a concentration-dependent manner. (−)3-PPP ( 3 × 10 −5 M ) had similar effects, but was less potent than (+)3-PPP. (+)3-PPP ( 3 × 10 −5 M ) also inhibited the A-current and a calcium-dependent potassium current, but to a lesser degree than the M -current. Inhibition of the M-current by (+)3-PPP was not antagonized by atropine ( 10 −6M ), sulpiride ( 10 −6M ), or by the putative sigma antagonists 1, 3-di-O-tolylguanidine ( 3 × 10 −6and10 −5M ) and rimcazole ( 3 × 10 −6Mand10 −5M ). It is concluded that (+)3-PPP depolarizes sympathetic neurons of the mouse isolated hypogastric ganglion by inhibiting the M-current. (+)3-PPP also inhibits the A-current and calcium-dependent potassium current. Through these actions (+)3-PPP may increase evoked neurotransmitter release and potentiate neurogenic twitch contractions of the mouse isolated vas deferens, as previously reported.

Hypogastric ganglion perinatal development: evidence for androgen specificity via androgen receptors

The hypogastric ganglion (HG) has previously been shown to be sensitive to both the organizational and activational influences of testosterone. The current investigations examined whether testosterone exerts similar effects prenatally, whether these events are specifically controlled by androgen, and whether androgens might directly masculinize the HG. Prenatal treatment with an anti-androgen, flutamide, resulted in significant decreases in the adult levels of tyrosine hydroxylase (TH) activity, an index of postsynaptic noradrenergic ontogeny 3, and choline acetyltransferase (ChAT) activity, a marker for presynaptic terminal formation. In addition, testosterone propionate and dihydrotestosterone benzoate reversed the effects of neonatal castration on the development of TH and ChAT activities. In contrast estradiol benzoate was unable to restore enzyme activities. To determine whether the above observations might be produced by direct effects on the HG, androgen cytosol receptor characteristics were studied. Competition and saturation analyses demonstrate that the affinity and specificity of the androgen cytosol receptor in the HG are similar to that displayed in the pituitary, which has previously been shown to contain androgen receptors. These results suggest that the adult levels of TH and ChAT activities are organized during prenatal and early postnatal development. In addition, the organization of the HG appears to be androgen specific. The presence of cytosol androgen receptors suggests that the organizational effects of androgens are possibly induced by a direct mechanism.

Organizational role of testosterone on the biochemical and morphological development of the hypogastric ganglion

Previous reports have demonstrated that after postnatal day 10 testosterone influences hypogastric ganglion (HG) development by ‘activating’ morphological and biochemical indices. We now report an ‘organizational’ influence on the developing HG during the first 10 postnatal days. To investigate the organizational effects of testosterone, male rats were castrated within 12 h of birth. Testosterone replacement theraphy initiated following castration maintained the normal number of neurons in the HG. Conversely, delayed replacement therapy starting at day 10 or vehicle treatment only, resulted in a significant decrease in neuron number. Castration also produced a significant decrease in somal and nuclear cross-sectional areas. Testosterone replacement, whether initiated immediately or if delayed until day 10, restored somal and nuclear cross-sectional areas to normal. Tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) activities were sensitive to both testosterone dosage and the time of administration. Testosterone decanoate administered subsequent to castration was not able to completely reverse the enzyme activity deficits, while delayed replacement theraphy was even less effective in restoring enzyme activities. In contrast, higher doses of testosterone completely reversed enzyme activity deficits, and in fact produced a significant increase in TH activity. Again, delayed testosterone replacement did not fully restore deficits in enzyme activity. In summary, the hormonal environment during the first 10 days of life is critical for the organization of HG cell number; in contrast, nuclear and cell size appear to be dependent on testosterone for activation. TH and ChAT activities also appear to be organized during this dose- and time-dependent developmental period.

Biochemical and morphological effects of castration on the postorganizational development of the hypogastric ganglion

The biochemical and morphological development of the sympathetic hypogastric ganglion (HG) was examined subsequent to postnatal castration at 10–11 days of age. Previous studies suggested that tyrosine hydroxylase (T-OH) activity, an index of noradrenergic maturation5, and choline acetyltransferase (ChAT) activity, a marker for preganglionic terminal formation5, were dependent on gonadal hormones during normal ontogeny. In the present studies, morphometric analyses of the HG revealed that the cross-sectional area of the cell soma and nucleus were significantly reduced following postnatal castration at day 10. Conversely, castration produced no change in the number of HG neurons. In addition, postnatal castration prevents the development of postsynaptic T-OH activity to a greater extent than ganglionic protein resulting in a significant loss of T-OH specific activity. In contrast, presynaptic ChAT activity was reduced in parallel with ganglionic protein, thus ChAT specific activity was unchanged. Testosterone replacement therapy, even in groups where treatment was delayed for up to 2 weeks after castration, completely reversed deficits in both T-OH and ChAT activities. These studies suggest that altered development of ganglion protein subsequent to postnatal castration is related to decreases in the size of neurons and not to the loss of neurons. The lack of cell loss also suggest that decreased levels of postsynaptic T-OH activity results from a loss of enzyme activity per cell and the decreased levels of ChAT activity probably represent fewer presynaptic terminals per neuron. In addition, delayed testosterone replacement subsequent to castration was effective in restoring enzyme activities suggesting an ‘activational’ not ‘organizational’ role for testosterone after postnatal day 10.

The major pelvic ganglion: androgen control of postnatal development

Previously we reported the effects of postnatal castration on the postorganizational development of the sympathetic hypogastric ganglion (Hamill and Guernsey, 1983; Melvin and Hamill, 1986). "Postorganization" implies an activational role for gonadal hormones, in contrast to the permanent organizing effects that occur perinatally. We now report results that suggest that the major pelvic ganglion (PG), a mixed parasympathetic and sympathetic ganglion, is similarly regulated by testosterone during development. Choline acetyltransferase (CAT) and tyrosine hydroxylase (T-OH) activities were used to examine normal PG ontogeny. The normal development of these biochemical indices occurs primarily after day 10. Postnatal castration at 10-11 d of age completely prevented the postorganizational developmental increase of T-OH activity. At 12 postoperative weeks T-OH activity in castrates was approximately 6% that of the control animals (control, 2880 +/- 127 pmol/ganglion X hr; castrated, 161 +/- 16 pmol/ganglion X hr; p less than 0.001). In fact, by only 1 postoperative week, T-OH activity was already significantly reduced in castrated animals (control, 480 +/- 69 pmol/ganglion X hr; castrated, 179 +/- 6 pmol/ganglion X hr; p less than 0.001). CAT activity and total ganglion protein were also significantly reduced by 1 postoperative week. In contrast to T-OH activity, however, these indices continued to develop at diminished rates. By 12 postoperative weeks CAT activity and total ganglion protein in castrates were 30 and 50% of control values, respectively, resulting in a significant developmental abnormality in CAT-specific activity. Testosterone replacement reversed the castration-induced developmental deficits of T-OH and CAT activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Laterality associated with sexual dimorphism in the volume of the mouse hypogastric ganglion

The volume of the hypogastric ganglion was investigated in male, female, and prenatally androgen-exposed female newborn mice. Two milligram testosterone propionate was injected into pregnant ICR mice from days 14 to 16 of gestation. The volume of the ganglia on both sides in intact male neonates was significantly larger than that in female neonates. The volume of ganglia in testosterone-exposed females was significantly larger than those in intact females, but did not attain the male volume. In intact males, the ganglion on the left side was significantly larger than on the right. This left-right difference in the volume of the ganglia was not recognized in the intact or TP-exposed females. These results suggest that sex difference and lateralization of the volume of the hypogastric ganglion were highly dependent on the prenatal sex hormone environment.

Gonadal hormone regulation of neurotransmitter synthesizing enzymes in the developing hypogastric ganglion

The effects of postnatal castration at 10–11 days of age were examined in the sympathetic hypogastric ganglion (HG). Assays for choline acetyltransferase (ChAT) activity, a biochemical marker for presynaptic cholinergic maturation, and the activity of tyrosine hydroxylase (T-OH), the rate limiting enzyme in postsynaptic catecholamine biosynthesis and an index of noradrenergic development, were employed to monitor HG ontogeny. After 1 postoperative week ChAT activity and T-OH activity were significantly reduced in castrated animals as compared to sham operated controls. Over the 12 week postoperative observation period T-OH activity never varied significantly from the day 10 precastration value; thus, by 12 postoperative weeks T-OH activity in the castrated animals was 3% of the control value. In contrast, ChAT activity and total ganglion protein continued to mature in the castrated animals, but at diminished rates, so that by 12 postoperative weeks both indices were approximately 40% of the control values. Testosterone replacement therapy restored both ChAT and T-OH activities to control levels. Additionally, testosterone replacement restored the control level of activity for DOPA decar☐ylase, a catecholamine synthetic enzyme which is differentially regulated from T-OH. The failure of enzyme activities to develop normally subsequent to castration on postnatal day 10 suggests that testosterone regulates the postorganizational maturation of postsynaptic noradrenergic enzyme activities and presynaptic ChAT activity.

Neuropeptide Y (NPY)-like immunoreactivity in rat sympathetic neurons and small granule-containing cells

The distribution of neuropeptide Y-like immunoreactivity (NPY-LI) was examined in the rat superior cervical and hypogastric ganglia. NPY-LI was localized in the majority of the sympathetic neurons, a few small granule-containing (SGC) cells and nerve terminals. Most of the NPY-immunoreactive sympathetic neurons were also tyrosine hydroxylase (TH)-immunoreactive but in hypogastric ganglia few neurons with NPY-LI were devoid of TH-immunoreactivity. Electron microscopically NPY-LI was found in the Golgi complexes of sympathetic neurons, in large cytoplasmic granules (100–150 nm in diameter) of the SGC cells and in large dense-cored vesicles (80–100 nm in diameter) of the nerve terminals. NPY-LI coexists mainly with noradrenaline in sympathetic neurons, and may have regulatory functions in sympathetic ganglia and in target organs.

Indices of neurotransmitter synthesis and release in aging sympathetic nervous system

Activities of tyrosine hydroxylase (TH),dopamine-β-hydroxylase (DBH) and choline acetyltransferase (ChAT) were assayed in sympathetic ganglia and adrenal glands of young and aged Fischer-344 rats. The recovery of reserpine-depleted catecholamine stores and catecholamine loss following inhibition of synthesis and intraneuronal degradation also were assessed in sympathetic ganglia of young and aged rats. No age differences were observed in DBH activity of any tissues examined or in the activities of any enzymes in the coeliac-mesenteric ganglion complex. However, TH and ChAT activities were significantly higher in the superior cervical ganglia and adrenal glands of aged rats. In the hypogastric ganglion, only TH activity was higher in the old rats. Recoveries of reserpine-depleted catecholamine stores in the superior cervical and hypogastric ganglia of aged rats were slower than in young rats. Catecholamine loss following inhibition of synthesis and intraneuronal degradation was faster in the superior cervical ganglia but not in the hypogastric ganglia of old rats as compared with young rats. These findings suggest that neurotransmitter synthesis and release are enhanced with age in the superior cervical ganglion. The lack of age-related changes in the hypogastric ganglion might reflect the different cellular composition as well as the physiological role of this ganglion.

Electrophysiological analysis of kappa opiate receptor activation in the rabbit vas deferens

Kappa (κ) opiate receptor agonists depress neuro-effector transmission in the rabbit vas deferens. We have been unable to observe any effect of U50488 or dynorphin 1–17 on the resting membrane potential, input resistance or action potential shape of hypogastric ganglion cells which innervate the rabbit vas deferens. It would appear that the terminals but not the somata of these neurones posess functional κ receptors. Excitability testing of the terminals failed to reveal a membrane hyperpolarisation induced by either U50488 or dynorphin 1–17. This would be compatible with the view that κ agonists, unlike μ agonists, inhibit neuronal transmission by directly inhibiting calcium influx.

Bombesin/gastrin-releasing peptide (GRP)- and Met5-enkephalin-Arg6-Gly7-Leu8-like immunoreactivities in small intensely fluorescent (SIF) cells and nerve fibers of rat sympathetic ganglia.

Superior cervical and hypogastric ganglia were removed from rats that had been perfused with a mixture of 4% paraformaldehyde and 0.25% glutaraldehyde. Specific antisera against Met5-enkephalin-Arg6-Gly7-Leu8 (MEAGL) and bombesin/gastrin-releasing peptide (BN/GRP) were used in the immunofluorescence procedure. In hypogastric ganglia, a subpopulation of small intensely fluorescent (SIF) cells, as identified by their aqueous aldehyde (Faglu)-induced fluorescence, showed MEAGL- and BN/GRP-like immunolabeling. SIF cells in the superior cervical ganglia were unlabeled. In both ganglia, varicose nerve fiber networks and nerve terminals surrounding principal ganglion cells showed MEAGL- and BN/GRP-like immunoreactivities. Unlabeled SIF cells often were in close contact with nerve fibers that had MEAGL-like immunolabeling. Immunoreactivities against MEAGL- and BN/GRP-like neuropeptides in nerve fibers and terminals suggest a neurotransmitter or neuromodulator role for these peptides. In addition, labeling in SIF cells implies their possible endocrine function.

Histochemically demonstrable catecholamines in sympathetic ganglia and carotid body of spontaneously hypertensive and normotensive rats.

The catecholamine content and morphology of the superior cervical and the hypogastric ganglion and the carotid body were studied in Spontaneously Hypertensive Rats (SHR) before (at the age of 6 weeks) and after (at the age of 20 weeks) becoming hypertensive, with Wistar Kyoto (WKY) rats as controls. The study was performed by formaldehyde-induced fluorescence method combined with quantitative microfluorimetry of catecholamines. At the age of 6 weeks the only significant difference observed between the rat strains was a greater number of small intensely fluorescent (SIF) cells in the superior cervical ganglion of SHR. At the age of 20 weeks the fluorescence intensity was higher in the principal neurons of the superior cervical ganglion and in glomus cells of the carotid body of SHR compared to WKY. The volumes of superior cervical ganglion and carotid body were larger in 20-week-old SHR compared to WKY. In the hypogastric ganglion differences were not found between SHR and WKY rats. The present results show differences in the superior cervical ganglion and in the carotid body of adult SHR compared to controls. These differences develop during the time period when the SHR become hypertensive, and might be functionally significant in the regulation or maintenance of the increased blood pressure in SHR rats.

The effect of aging on extra-adrenal catecholamine storing cells of the rat

—Cell number and catecholamine histofluorescence were determined in three extra-adrenal chromaffin tissues: the abdominal paraganglia, the carotid body and SIF (small intensely fluorescent)-cells, of male Fischer-344 rats at different ages. Catecholamines were demonstrated using the formaldehyde-induced fluorescence method. The number of paraganglia cells in the retroperitoneal area increased 13.6 fold between 3 and 33 months of age, and the volume of abdominal paraganglia approached 65% of the volume of one adrenal medulla. The emission color of some paraganglia cells shifted from greenish-yellow to yellowish-brown with aging, but differences were not observed in cell number or fluorophore color in the carotid body, a chemoreceptor type of paraganglion. The number of SIF cells (an intraganglionic variant of extra-adrenal chromaffin tissue) in the hypogastric ganglion increased significantly between 3 and 33 months. The pronounced increase of the volume of the paraganglia in aged rats may contribute to elevated concentrations of circulating catecholamines in these animals.

P-197) - The effects of different calcium concentrations on the inhibitory potency of noradrenaline in the synaptic transmission of the guinea-pig hypogastric ganglion

P-197) - The effects of different calcium concentrations on the inhibitory potency of noradrenaline in the synaptic transmission of the guinea-pig hypogastric ganglion

Hormonal regulation of sympathetic neuron development. The effects of neonatal castration

The effects of neonatal castration on neuronal ontogeny were examined in peripheral sympathetic ganglia in male Sprague-Dawley rats. Tyrosine hydroxylase (T-OH) activity, the rate-limiting enzyme in catecholamine biosynthesis and a marker of noradrenergic maturation, was examined in the hypogastric (HG) and superior cervical ganglion (SCG). Initial studies characterized the normal development of T-OH activity in HG ganglia. Neonatal castration at 10–11 days of age prevented the normal ontogeny of HG T-OH activity: T-OH activity failed to develop normally and was 17% of sham-operated littermate controls when examined at 8 weeks of age, and less than 5% when studied 10 weeks after surgery. In contrast to the effects in HG, there was no change in enzyme activity in the SCG. Replacement therapy with testosterone decanoate completely reversed the developmental alteration in enzyme activity. These observations suggest that hormonal factors modulate noradrenergic ontogeny in peripheral sympathetic ganglia but these effects appear restricted to ganglia whose targets include hormonally dependent sex organs.

Prenatal exposure of male mice to androgen increases neuron number in the hypogastric ganglion

There is a sexual dimorphism in the hypogastric ganglion innervating the internal genitalia of mice. We now report that prenatal exposure of male mice to testosterone propionate brings about a significant increase of neuronal number in the hypogastric ganglion. This suggests that sexually dimorphic nature of the hypograstric ganglion depends on the prenatal hormone environment.

Studies of frequency-dependent inhibition of noradrenaline on the hypogastric ganglion of the guinea pig

In previous studies, we showed that selective application of noradrenaline (NA) to the ganglion in the hypogastric nerve-vas deferens preparation of the guinea pig inhibited twitch-like response of the muscle to preganglionic nerve stimulation at low frequencies(stimulation was for period of 2 sec at 2min intervals at frequency of 2 to 50Hz with a pulse duration of 0.1msec), and the ganglion depressant effectiveness of NA increased with decreasing stimulation of frequency. These findings were obtained on the condition that a period of stimulation was held constant. An alteration of frequency in a fixed stimulation-period means change of both the interval between pulses and the number of pulses. The purpose of this study is to elucidate a relationship between these two stimulation parameters and the depressant effect of NA. Since the twitch-like response to the nerve stimulation increased with extending stimulation-period within 2sec and since the same response attained maximum at frequency of 20Hz, the effect of NA was examined on the response to the stimulation at frequency of 2 to 20Hz on the condition that the stimulation-period was within 2sec. When the pulse-number was kept constant and the pulse-interval was altered, NA produced equivalent inhibition of the response. In a fixed pulse-interval, the effectiveness of NA decreased with increasing pulse-number. With the same condition, NA did not block the response to nerve stimulation with a 40pulse train at pulse-interval of 50msec. These results suggest that the depressant action of NA on the guinea-pig hypogastric ganglion is pulse-number dependent.

Developmental changes of the hypogastric ganglion associated with the differentiation of the reproductive tracts in the mouse

Prenatal exposure of male or female mice to diethylstilbestrol (DES) or testosterone propionate (TP) from days 9 to 16 of gestation products pseudohermaphrodites with dual reproductive tracts. In these animals, the hypogastric ganglion which is thought to innervate the internal genitalia was examined at birth. The number of ganglion cells was significantly larger in prenatally DES-exposed male and TP-exposed female mice than that of controls. These results suggest that the number of hypogastric ganglion cells is dependent on the number of the target organs for innvervation.

Glucose utilization in sympathetic ganglia of male Fischer-344 rats at different ages.

The relation of glucose utilization to age was studied with the [14C]2-deoxy-D-glucose method in 3 peripheral sympathetic ganglia of conscious male Fischer-344 rats. The hypogastric ganglion, coeliac-mesenteric ganglion complex and superior cervical ganglion were examined in 3-, 12-, 24- and 30-33-month-old animals. Glucose utilization increased significantly between 12 and 30-33 months in the superior cervical ganglion and between 3 and 24 months in the coeliac-mesenteric ganglion complex. No significant, age-related changes were observed in the hypogastric ganglion. In addition, neuron density decreased significantly between 3 and 12 months in the hypogastric ganglion and between 3 and 30-33 months in the coeliac-mesenteric ganglion complex, but no changes were observed in the superior cervical ganglion. Despite the increased glucose utilization in the superior cervical ganglion, heart rate decreased between 12 and 24 months, and mean arterial blood pressure decreased between 24 and 30-33 months. The results suggest that functional activity of some sympathetic ganglia increases in older rats, although end organ effects may be reduced.