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Biomedical subjects

G Ju

Publications and source records attributed to G Ju.

At least 55 records · Page 3Linked to original sources

IL-1 receptor accessory protein is an essential component of the IL-1 receptor.

The recently described IL-1R accessory protein (IL-1R AcP) interacts with IL-1beta and the IL-1 type-IR (IL-1RI), but an essential requirement for IL-1R AcP in IL-1 signaling in vitro has not been established and its role in vivo has not been examined. In this study, IL-1R AcP-deficient mice and fibroblasts were produced and characterized. All IL-1 agonists bound to IL-1R AcP-deficient cells through the type I IL-1R, but failed to activate gene expression through either the nuclear factor-kappaB or AP-1-dependent signaling pathways. Absence of IL-1R AcP differentially affected the affinity for IL-1 ligands. IL-1R AcP-deficient fibroblasts bound murine IL-1alpha and human IL-1R antagonist protein (IL-1Ra) with only moderately reduced affinity when compared with wild-type cells, whereas murine IL-1beta affinity was reduced by 70-fold. IL-1 also failed to produce a biologic response in vivo in IL-1R AcP-deficient mice. These data demonstrate that a type I IL-1R/IL-1R AcP complex is required for signaling by all IL-1 agonists and for high affinity binding by IL-1beta. Finally, IL-1R AcP is an essential signal transducing component of the functional IL-1R and should represent a novel target for blocking IL-1 function in human disease.

Animals↗

The organization of chemically characterized afferents to the perivascular neuronal groups of the hypothalamic magnocellular neurosecretory system in the rat.

The hypothalamic magnocellular neurosecretory system consists of the paraventricular nucleus and supraoptic nucleus and a number of accessory nuclei. There is evidence that each of the accessory nuclei has a preferential source of afferents. Two of the accessory nuclei, namely the nucleus circularis (NC) and the lateral hypothalamic perivascular nucleus (LHPN), are particularly interesting due to their very close relationship with the blood vessels. The NC is composed of small dense clusters of neurons in the medial anterior hypothalamus. The groups of lateral hypothalamic neurons gathering around vascular branches are collectively called the LHPN. Their close topographical relationship with the blood vessels may indicate that the latter may serve as a source of input to these nuclei. As a part of the effort to investigate this issue, the present study examined in these two nuclei the distribution pattern of terminal-like elements containing 11 transmitters/modulators. Only a few, if any, terminal-like elements of the transmitters/modulators studied could be found distributed in the NC proper, although its immediate vicinity could be densely innervated. On the contrary, the LHPN proper was often densely innervated by fibers expressing the examined markers. These terminal patterns were found to be quite different from those of the paraventricular and supraoptic nuclei. The present findings further substantiate the notion of a functional differentiation among the subnuclei of the magnocellular neurosecretory system. The significance of the relationship of these two perivascular nuclei with the blood vessels is discussed.

Animals↗

Regulation of expression of neuropeptide Y Y1 and Y2 receptors in the arcuate nucleus of fasted rats.

Neuropeptide Y is expressed in neurons of the hypothalamic arcuate nucleus and has been ascribed a role as a stimulant of food intake. Neuropeptide Y Y1 and Y2 receptors are also localised in the arcuate nucleus, and it has been suggested that the Y1 receptor mediates part of the effect of neuropeptide Y on feeding behaviour. In the present study, immunohistochemistry and in situ hybridization were used to investigate the effect of food deprivation on the expression of Y1 and Y2 receptors in the arcuate nucleus of the rat. Fasting for 48 h induced a decrease in the number and area of Y1 receptor immunoreactive neurons in the arcuate nucleus. Furthermore, arcuate Y1 receptor mRNA levels also decreased after food deprivation. The decrease in the number of the Y1 receptor immunoreactive neurons was partially attenuated by supplementing the drinking water with 10% glucose. In contrast, fasting did not significantly change Y2 receptor mRNA levels in the arcuate nucleus. These results support the view that Y1 receptors in the arcuate nucleus play a role in the feeding pattern induced by neuropeptide Y.

Animals↗

Synaptoid contacts between gland cells of the anterior pituitary of the rat.

BACKGROUND: There is evidence suggesting cross-talk among gland cells of the anterior pituitary. We had reported a rare form of synaptoid contact between corticotrophs in the anterior pituitary of the dog. We then found similar synaptoid contacts with different characteristics in the rat, as described in the present article. METHODS: Male Sprague-Dawley rats were used. The anterior pituitaries were prepared for ultrastructural study of substance P immunoreactivity of the anterior pituitary. Routine preembedding immunohistochemical staining was conducted, the sections were embedded in Epon 812 (Serva Feinbiochemica, Heidelberg, New York), and ultrathin sections were prepared. RESULTS: In the anterior pituitary of the rat, synaptoid contacts were found between corticotrophs and lactotrophs. They appeared very close to typical synapses in the central nervous system, aside from evident weakness of presynaptic density. CONCLUSIONS: The presence of synaptoid contacts suggests a form of cross-talk between the gland cells in the anterior pituitary of the rat.

Animals↗

Galanin-like immunoreactive nerve fibres in the anterior pituitary of the normal and adrenalectomized rat.

Our previous studies have shown the presence of substantial amounts of substance P and calcitonin gene-related peptide-like immunoreactive nerve fibres in the anterior pituitary of the monkey, dog and rat. Furthermore, synaptic relationships have been demonstrated between these nerve fibres and the gland cells in the dog and rat. The substance P and calcitonin gene-related nerve fibres increase in number following adrenalectomy and ovariectomy, respectively. The present study was aimed to investigate the galanin-containing nerve fibres in the anterior pituitary of normal and adrenalectomized rats. The results showed only a small amount of galanin-like immunoreactive nerve fibres in the normal anterior pituitary, which were present among the gland cells as well as along the blood vessels. Following adrenalectomy, the number of galanin-like immunoreactive nerve fibres increased and ramification appeared more frequently. The results substantiate our hypothesis of a dual neural-humoral regulation of the mammalian anterior pituitary gland.

Adrenalectomy↗

Down-regulation of mu-opioid receptors in rat and monkey dorsal root ganglion neurons and spinal cord after peripheral axotomy.

To understand the role of opioids and their receptors in chronic pain following peripheral nerve injury, we have studied the mu-opioid receptor in rat and monkey lumbar 4 and 5 dorsal root ganglion neurons and the superficial dorsal horn of the spinal cord under normal circumstances and after peripheral axotomy. Our results show that many small neurons in rat and monkey dorsal root ganglia, and some medium-sized and large neurons in rat dorsal root ganglia, express mu-opioid receptor-like immunoreactivity. Most of these neurons contain calcitonin gene-related peptide. The mu-opioid receptor was closely associated with the somatic plasmalemma of the dorsal root ganglion neurons. Both mu-opioid receptor-immunoreactive nerve fibers and cell bodies were observed in lamina II of the dorsal horn. The highest intensity of mu-opioid receptor-like immunoreactivity was observed in the deep part of lamina II. Most mu-opioid receptor-like immunoreactivity in the dorsal horn originated from spinal neurons. A few mu-opioid receptor-positive peripheral afferent terminals in the rat and monkey dorsal horn were calcitonin gene-related peptide-immunoreactive. In addition to pre- and post-junctional receptors in rat and monkey dorsal horn neurons, mu-opioid receptors were localized on the presynaptic membrane of some synapses of primary afferent terminals in the monkey dorsal horn. Peripheral axotomy caused a reduction in the number and intensity of mu-opioid receptor-positive neurons in the rat and monkey dorsal root ganglia, and of mu-opioid receptor-like immunoreactivity in the dorsal horn of the spinal cord. The decrease in mu-opioid receptor-like immunoreactivity was more pronounced in the monkey than in the rat dorsal root ganglia and spinal cord. It is probable that there was a parallel trans-synaptic down-regulation of mu-opioid-like immunoreactivity in local dorsal horn neurons of the monkey. These data suggest that one factor underlying the well known insensitivity of neuropathic pain to opioid analgesics could be due to a marked reduction in the number of mu-opioid receptors in the axotomized sensory neurons and in interneurons in the dorsal horn of the spinal cord.

Animals↗

Distribution of SPR-like immunoreactivity in the medullary visceral zone of the rat and changes following acute myocardial ischemia induced by intravenous injection of vasopressin.

Substance P receptor-like immunoreactive (SPR-LI) structures and changes following intravenous injection of vasopressin in the medullary visceral zone (MVZ) of the rat were studied by using immunohistochemical methods. In normal control rats the distribution of SPR-LI structure in MVZ generally matched with that of immunostaining against substance P (SP-LI) except in some areas. SPR-LI neurons and dendrites differed in size and shape in different areas of MVZ. Their dendrites could be classified into three types, i.e, wool-shaped, smooth and varicose. Some SPR-LI neurons were also positive for tyrosine hydroxylase-like immunoreactivity (TH-LI) . After administration of vasopressin SPR-LI structures became denser, especially at levels of pyramidal decussation (PYX) and area postrema (AP). The dendrites of motor dorsal nucleus of X (NMDX) in the dorsal part of MVZ appeared thin and straight in morphology instead of curl and thick outlooks. These results implicate that some SPR-LI neurons might be involved in the modulation of the cardiovascular stress induced by vasopressin.

Acute Disease↗

Evidence of direct neural regulation of the anterior hypophysis reproductive functions.

It is generally acknowledged that the anterior hypophysis is not directly regulated by neural elements. Our studies in the past decade, however, have demonstrated otherwise. The anterior pituitary gland has been found to be actually under neural-humoral dual regulation. The present article outlines the main data that have led us to this conclusion. Evidence that is related to direct neural regulation of the reproductive functions of the anterior hypophysis is provided in great detail. Thus, synapses have been demonstrated between the nerve fibers innervating the anterior pituitary gland and the gonadotropes and lactotropes. Furthermore, there is ultrastructural evidence indicating that synaptic activities may induce secretion of the gland cells. Hormone manipulation study shows that following ovariectomy there is a significant increase of nerve fibers in the anterior pituitary gland, which is related to plasma estrogen level.

Adrenalectomy↗

Innervation of the mammalian anterior pituitary: a mini review.

The mammalian anterior pituitary was not known to be innervated other than by a few autonomic nerve fibers. Recent studies, however, have demonstrated otherwise. A hypothesis of neural-humoral dual regulation of the mammalian anterior pituitary has been postulated based on the following findings: (1) the presence of substantial amounts of nerve fibers in the anterior pituitary of a number of mammalian species; (2) close contact of the nerve fibers with the gland cells, even forming synapses; (3) the nerve fibers originate, as least partly, from the hypothalamus; (4) the nerve fibers respond actively to changes in hormonal levels of the organism; and (5) stimulation of the nerve fibers changes the secretory activities of the gland cells.

Adrenalectomy↗

Expression and regulation of the neuropeptide Y Y2 receptor in sensory and autonomic ganglia.

The Y2 subtype of neuropeptide tyrosine (NPY) receptors (Y2R) and some neuropeptides have been studied with in situ hybridization in sensory and autonomic neurons of rat and monkey. Between 10% and 20% of the lumbar dorsal root ganglion (DRG) neuron profiles (NPs) contain Y2R mRNA in the rat and monkey. In rat DRGs Y2R mRNA is expressed in calcitonin gene-related peptide (CGRP)-positive, medium-sized, and large neurons, that is in a complementary fashion to the Y1R that is located in small CGRP neurons. In monkey DRGs Y2R mRNA is expressed mainly in small neurons. Peripheral axotomy up-regulates the Y2R in small and large DRG neurons in both species. Y2R and NPY mRNAs are colocalized in many large neurons in axotomized rat DRGs. Y2R mRNA is expressed in 50% of the NPs in the nodose ganglion with a modest increase after axotomy. Y2R mRNA is detected in a few NPs in normal rat superior cervical ganglia, with a marked increase after transection of the carotid nerves. No Y2R mRNA-positive, but many (approximately 30%) weakly Y1R mRNA-positive NPs were found in the sphenopalatine ganglion. Finally, Y2R mRNA levels increase in rat spinal motoneurons after axotomy. Thus, under normal circumstances NPY may act on Y1 and Y2Rs expressed, respectively, in small and large CGRP-positive DRG neurons in the rat. Y2R may be an important receptor in the viscero-sensory neurons. Y2Rs may be particularly important after axotomy serving as presynaptic and/or autoreceptors on rat DRG, superior cervical ganglion, and nodose ganglion neurons and as presynaptic receptors in monkey DRG neurons.

Animals↗

Nitric oxide inhibits neuronal activity in the supraoptic nucleus of the rat hypothalamic slices.

The presence of abundant nitric oxide synthase (NOS) in magnocellular neurons of the rat hypothalamus suggests that nitric oxide (NO) may be involved in controlling the release of oxytocin and vasopressin. To test this possibility, we examined the effect of NO-related drugs on extracellular discharges of 124 supraoptic nucleus (SON) neurons from slices of rat hypothalamus in vitro. Twenty-three (43%) of 53 neurons were inhibited by sodium nitroprusside (SNP), a spontaneous releaser of NO, at 1-3 mM. This inhibition was prevented by preincubation of the slices with 1 microM hemoglobin, an inactivator of NO (n = 14), whereas hemoglobin alone enhanced neuronal activity in seven (35%) of 20 neurons. L-Arginine (1 mM), a precursor of NO, inhibited neuronal activity in five (36%) of 14 neurons, while D-arginine (1 mM), the inactive counterpart of L-arginine, was ineffective (n = 12). N-omega-nitro-L-arginine methyl ester (L-NAME, 10 microM), an inhibitor of NOS, also enhanced neuronal activity in five (29%) of 17 neurons, while N-omega-nitro-D-arginine methyl ester (DNAME, 10 microM), the inactive enantiomer of L-NAME, was without effect (n = 11). Together, our data show that NO exerts predominantly an inhibitory effect on SON neurons and may serve as a negative feedback loop in controlling release of oxytocin and vasopressin.

Animals↗

Response of substance P-immunoreactive nerve fibres in the anterior pituitary to plasma oestrogen levels in the rat.

The mammalian anterior pituitary has recently been shown to be innervated by substantial amounts of peptidergic nerve fibres. It has also been found that adrenalectomy increases the amount of calcitonin gene-related peptide-like immunoreactive nerve fibres in the anterior pituitary of the rat, and that stimulation of the nerve fibres in vitro can enhance release of ACTH. In the present study, the density of substance P-like immunoreactive nerve fibres in the anterior pituitary of the rat were examined in relation to variations in plasma oestrogen status. The amount of substance P-like immunoreactive nerve fibres increased significantly (P < 0.001) after ovariectomy, and decreased significantly (P < 0.01) under oestrogen replacement, in a dose-dependent manner. The results suggest the possibility of the direct neural involvement of oestrogen secretion in anterior pituitary regulation, which further substantiates the hypothesis of neural-humoral dual regulation of the mammalian anterior pituitary.

Animals↗

Prevention of kainic acid-induced limbic seizures and Fos expression by the GABA-A receptor agonist muscimol.

Fos oncoprotein expression has been shown to be a sensitive marker for sequential neuronal activation in response to a specific stimulus. The present study investigated the effect of the gamma-aminobutyric acid (GABA)-A receptor agonist muscimol on kainic acid (KA)-induced limbic seizures and Fos expression in the rat forebrain. One hour after KA injection, a substantial Fos expression was observed in the hippocampal dentate gyrus, whereas only a low level of Fos induction was seen in CA1-3 fields. Six hours post-injection a prominent increase of Fos expression occurred in most forebrain structures, including the whole hippocampus. Following 0.5 mg/kg muscimol treatment a remarkable decrease of Fos expression occurred but only in the caudate putamen and core of the accumbens nucleus. Treatment with 1 mg/kg muscimol led to further significant decreases of Fos expression in CA1-3 pyramidal neurons and the disappearance of Fos induction in the cerebral cortex above the rhinal fissure, reticular thalamic nucleus, claustrum, fundus striati, ventral pallidum, septal nucleus, lateral habenular nucleus, and lateral amygdaloid nucleus. When 2 mg/kg muscimol was injected, animals exhibited "absence seizures' instead of limbic seizures, and Fos expression in the hippocampus was effectively blocked. These results suggest that a reduction of GABAergic inhibition plays a crucial role not only in limbic seizure genesis in the dentate gyrus, but also in the seizure spread mechanism in many brain structures, among which the hippocampal CA1-3 fields are most markedly involved, less marked in the cerebral cortex and some other structures, and least marked in the caudate putamen and core of the accumbens nucleus.

Animals↗

[The discovery of pituitary adenylate cyclase activating polypeptide (PACAP) and its research progress].

Pituitary adenylate cyclase activating polypeptide(PACAP) is a new bioactive polypeptide originally isolated from ovine hypothalamus. It is widely distributed in the central and peripheral nervous systems, and some non-nervous tissues as well. Mediated by PACAP receptors, it stimulates adenylate cyclase and subsequently increases the cAMP level in target cells. PACAP is not only a new type of hypophysiotropic hormone, but also functions as a neurotransmitter and neuromodulator. In addition, it plays a role in paracrine and autocrine regulation of certain types of cells.

Amino Acid Sequence↗

[Ceramide pathway].

Ceramide may be generated from many metabolism routes. As a novel second messenger, ceramide plays important roles in a variety of physiologic or pathologic events relating to cellular growth, proliferation, differentiation, apoptosis and injuries. It is expected that new insights into the ceramide pathway would promote our understanding of the complex mechanisms for signal transduction.

Animals↗

[Effects of spinal cord extract on neurite growth of GABAergic and dynergic neurons of spinal cord in vitro].

We use the crude extract from human fetal spinal cord to study the effect of endogenous substances of the spinal cord on neurite growth of E 12-15 mouse GABAergic and DNYergic neurons of the spinal cord in vitro. The results indicated that the crude extract had no effect on GABAergic neurons but had markedly neurite-promoting effect on DNYergic neurons when the protein concentration of the crude extract was 250 micrograms/ml. It suggests that there are endogenous substances in the crude extract of the human fetal spinal cord, which can promote neurite growth of spinal cord neurons and this effect is neuron type specific at particular embryonic age.

Animals↗