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1.
Nesfatin-1 is one of the peptide products of posttranslational processing of the nucleobindin-2 (NUCB2) gene, suggested to have physiological relevance to suppress food intake and body weight gain in rats. Nesfatin-1-immunoreactive cells have been found in distinct nuclei in the rat brain related to circuitries regulating food intake. Here, we report novel yet undescribed localization of NUCB2/nesfatin-1 at the mRNA and protein level in the rat central nervous system. Immunohistochemical staining revealed the localization of NUCB2/nesfatin-1 in the piriform and insular cortex, endopiriform nucleus, nucleus accumbens, lateral septum, bed nucleus of stria terminalis, central amygdaloid nucleus, medial preoptic area, dorsal raphe nucleus, ambiguus nucleus, ventrolateral medulla and gigantocellular reticular nucleus, as well as Purkinje-cells of the cerebellum. In the spinal cord, nesfatin-1 immunoreactivity (IR) was found in both sympathetic and parasympathetic preganglionic neuronal groups and in the dorsal area X from lower thoracic to sacral segments. The immunohistochemical results were confirmed by RT-PCR in the central amygdaloid nucleus, nucleus accumbens, cerebellum and lumbar spinal cord microdissected by punch technique. The features and distributions of nesfatin-1 IR and mRNA expression in the brain and spinal cord suggest that NUCB2/nesfatin-1 could play a wider role in autonomic regulation of visceral-endocrine functions besides food intake.  相似文献   

2.
The ontogenesis of the 1,25-dihydroxyvitamin D3 specific binding activity in intestine was examined in vitamin D-deficient and replete rats. The absence of binding activity in intestines during the first two postnatal weeks was not influenced by vitamin D supplementation. The concentration of binding sites peaked on day 18 in vitamin D-replete rats and preceded that in the deficient group by approximately 1 wk. The influence of glucocorticoids on 1,25-dihydroxyvitamin D3-binding protein levels was examined by sequential hydrocortisone administration and adrenalectomy. Subcutaneous hydrocortisone administration before day 14 postpartum did not induce binding activity. The concentration of binding sites was significantly increased to 369 +/- 60 fmol/mg of protein by hydrocortisone injections from days 15 to 17 postpartum when compared with an average of 182 +/- 16 fmol/mg of protein in littermate controls. Hydrocortisone administration did not further increase receptor levels in rats injected from days 19 to 21. Bilateral adrenalectomy on day 17 postpartum significantly decreased the concentration of binding sites. It is concluded that adrenal glucocorticoids play an important role in the developmental appearance of 1,25-dihydroxyvitamin D3 specific binding activity in the postnatal rat intestine.  相似文献   

3.
The function of local networks in the CNS depends upon both the connectivity between neurons and their intrinsic properties. An intrinsic property of spinal motoneurons is the presence of persistent inward currents (PICs), which are mediated by non-inactivating calcium (mainly CaV1.3) and/or sodium channels and serve to amplify neuronal input signals. It is of fundamental importance for the prediction of network function to determine the distribution of neurons possessing the ion channels that produce PICs. Although the distribution pattern of CaV1.3 immunoreactivity (CaV1.3-IR) has been studied in some specific central nervous regions in some species, so far no systematic investigations have been performed in both the rat spinal cord and brain stem. In the present study this issue was investigated by immunohistochemistry. The results indicated that the CaV1.3-IR neurons were widely distributed across different parts of the spinal cord and the brain stem although with variable labeling intensities. In the spinal gray matter large neurons in the ventral horn (presumably motoneurons) tended to display higher levels of immunoreactivity than smaller neurons in the dorsal horn. In the white matter, a subset of glial cells labeled by an oligodendrocyte marker was also CaV1.3-positive. In the brain stem, neurons in the motor nuclei appeared to have higher levels of immunoreactivity than those in the sensory nuclei. Moreover, a number of nuclei containing monoaminergic cells, for example the locus coeruleus, were also strongly immunoreactive. CaV1.3-IR was consistently detected in the neuronal perikarya regardless of the neuronal type. However, in the large neurons in the spinal ventral horn and the cranial motor nuclei the CaV1.3-IR was clearly detectable in first and second order dendrites. These results indicate that in the rat spinal cord and brain stem CaV1.3 is probably a common calcium channel used by many kinds of neurons to facilitate the neuronal information processing via certain intracellular mechanisms, for instance, PICs.  相似文献   

4.
Hereditary 1,25-dihydroxyvitamin D resistant rickets (HVDRR) is a genetic disorder most often caused by mutations in the vitamin D receptor (VDR). In this report, we present our findings on a young girl who exhibited the typical clinical features of HVDRR with early onset rickets, hypocalcemia, secondary hyperparathyroidism, and elevated serum concentrations of alkaline phosphatase and 1,25-dihydroxyvitamin D [1,25(OH)(2)D(3)]. The patient also had total body alopecia. Fibroblasts from the patient were cultured for analysis of the VDR structure and function. In [3H]1,25(OH)(2)D(3) binding assays, no significant specific binding to the VDR was observed in cytosols from the patient's fibroblasts. The patient's fibroblast were also totally resistant to high doses of 1,25(OH)(2)D(3) as demonstrated by their failure to induce expression of the 24-hydroxylase gene, a marker of 1,25(OH)(2)D(3) activity. DNA sequence analysis of the VDR gene uncovered a unique C to T mutation in exon 8. The mutation changed the codon for glutamine to a premature stop codon at amino acid 317 (Q317X). Restriction enzyme analysis showed that the patient was homozygous for the mutation. Both parents were heterozygous for the mutant allele. In conclusion, we have identified a novel mutation in the VDR, Q317X, as the molecular defect in a patient with HVDRR. The Q317X mutation deletes 110 amino acids of the ligand-binding domain of the VDR and results in the loss of [3H]1,25(OH)(2)D(3) binding and target gene transactivation.  相似文献   

5.
By using in situ hybridization histochemistry the distribution of growth hormone (GH) receptor mRNA was examined in the rat brain stem and spinal cord. Dense labeling was seen in the arcuate nucleus of the hypothalamus, as reported previously, but also in several other areas, including the locus coeruleus, the area postrema, and the commissural part of the nucleus of the solitary tract. Other labeled structures included the superior lateral parabrachial nucleus, the facial, hypoglossal and trigeminal motor nuclei, the nucleus incertus, the dorsal tegmental nucleus, the dorsal raphe nucleus, the nucleus of the trapezoid body, and the superficial layers of the dorsal horn of the spinal cord. These findings provide support for a direct action of GH on brain regions involved in various aspects of homeostatic control. Thus, the distribution of GH receptor mRNA to visceral sensory and motor structures is consonant with a role of GH in the regulation of food intake and energy homeostasis. Its presence in the superficial dorsal horn of the spinal cord indicates a role for GH in the initial processing of fine afferent input, and may help explain the beneficial effects of GH replacement in certain unclear pain conditions.  相似文献   

6.
Apparent [3H]1,25-dihydroxyvitamin D3 uptake by canine and rodent brain   总被引:2,自引:0,他引:2  
The brain uptake of [3H]1,25-dihydroxyvitamin D3 ([3H]1,25(OH)2D3) was studied during steady-state conditions using the multiple-indicator dilution technique in dogs. The fractional [3H]1,25(OH)2D3 uptake was evaluated at 0.8 +/- 0.15% during a single passage through the dog brain. Evaluation of the [3H]1,25(OH)2D3 uptake by the vitamin D-replete and vitamin D-depleted rat brain indicated that 30 min after its injection, the fractional uptake was not influenced by the vitamin D status of the animals or by the amount of [3H]-1,25(OH)2D3 injected. In the rodent the fractional [3H]-1,25(OH)2D3 brain accumulation was between 0.16 and 0.20%, whereas the brain-to-serum ratio varied between 5 and 6%. Protein-binding studies of serum [3H]1,25(OH)2D3 indicated that, at 37 degrees C, 94.8 +/- 0.4% of the hormone was protein bound 30 min after its intravenous injection. These observations suggest that 1,25(OH)2D3 is able to cross the blood-brain barrier. However, its limited brain uptake in relation to its serum concentration suggests that the hormone does not penetrate freely into the central nervous system and that its brain uptake may be related to the free circulating 1,25(OH)2D3 concentration perfusing the blood-brain barrier.  相似文献   

7.
《Acta histochemica》2019,121(8):151437
Neuronal NOS (nNOS) accounts for most of the NO production in the nervous system that modulates synaptic transmission and neuroplasticity. Although previous studies have selectively described the localisation of nNOS in specific brain regions, a comprehensive distribution profile of nNOS in the brain is lacking. Here we provided a detailed morphological characterization on the rostro-caudal distribution of neurons and fibres exhibiting positive nNOS-immunoreactivity in adult Sprague-Dawley rat brain. Our results demonstrated that neurons and fibres in the brain regions that exhibited high nNOS immunoreactivity include the olfactory-related areas, intermediate endopiriform nucleus, Islands of Calleja, subfornical organ, ventral lateral geniculate nucleus, parafascicular thalamic nucleus, superior colliculus, lateral terminal nucleus, pedunculopontine tegmental nucleus, periaqueductal gray, dorsal raphe nucleus, supragenual nucleus, nucleus of the trapezoid body, and the cerebellum. Moderate nNOS immunoreactivity was detected in the cerebral cortex, caudate putamen, hippocampus, thalamus, hypothalamus, amygdala, and the spinal cord. Finally, low NOS immunoreactivity were found in the corpus callosum, fornix, globus pallidus, anterior commissure, and the dorsal hippocampal commissure. In conclusion, this study provides a comprehensive view of the morphology and localisation of nNOS immunoreactivity in the brain that would contribute to a better understanding of the role played by nNOS in the brain.  相似文献   

8.
This report describes the presence and activity of 1,25-dihydroxyvitamin D3 (1,25-D3) in experimental bovine tuberculosis. Animals that went on to develop tuberculous lesions exhibited a rapid transient increase in serum 1,25-D3 within the first 2 weeks following infection with Mycobacterium bovis. 1,25-D3-positive mononuclear cells were later identified in all tuberculous granulomas by immunohistochemical staining of postmortem lymph node tissue. These results suggest a role for 1,25-D3 both at the onset of infection and in the development of the granuloma in these infected animals. Using a monoclonal antibody to the vitamin D receptor (VDR) as a VDR agonist, we confirmed that activation of the vitamin D pathway profoundly depresses antigen-specific, but not mitogenic, bovine peripheral blood T-cell responses (proliferation and gamma interferon production). Investigation of the mechanism of this suppression showed that the VDR antibody modified the expression of CD80 by accessory cells, such that a significant positive correlation between T-cell proliferation and accessory cell CD80 emerged.  相似文献   

9.
The endogenous opioid system, in particular the enkephalins, has been implicated in a vast array of neurological functions. The dog could be a suitable model for the study of complex interactions between behavioral state and regulatory physiology in which the opioid system appeared to be implicated. Moreover, opiate derivatives are currently used in veterinary clinic and sometimes pharmacologically tested in the dog. However, there are no anatomical data regarding the organization of the opioid system in this species. The present work represents the first attempt to map the distribution of Met5-enkephalin-like-immunoreactive (Met-enk-li) cell bodies and fibers in the diencephalon and the brainstem of the dog. In the diencephalon, labeled cells were present in all the mid-line and intralaminar thalamic nuclei; the lateral posterior, pulvinar and suprageniculate nuclei; the ventral nucleus of the lateral geniculate body and the medial geniculate body. Additionally, Met-enk-li cells were seen in every hypothalamic nucleus except in the supraoptic. Variable densities of labeled fibers were also seen in all these nuclei except in the medial geniculate body and in most areas of the lateral posterior and pulvinar nuclei. In the mesencephalon, positive cells were found in the periaqueductal gray, the Edinger–Westphal and interpeduncular nuclei, delimited areas of the superior and inferior colliculi and the ventral tegmental area. In the rhombencephalon, labeled cells were seen in the majority of the nuclei in the latero-dorsal pontine tegmentum, the nuclei of the lateral lemniscus, the trapezoid, vestibular medial, vestibular inferior and cochlear nuclei, the prepositus hypoglossal, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus, the infratrigeminal nucleus and the caudal part of the spinal trigeminal nucleus and in the rhombencephalic reticular formation. The distribution of fibers included additionally the substantia nigra, all the trigeminal nerve nuclei, the facial nucleus and a restricted portion of the inferior olive. These results are discussed with regard to previous reports on the distribution of Met-enk in other species.  相似文献   

10.
Alpha-neoendorphin (-NE) is an opiate decapeptide derived from the prodynorphin protein. Its anatomical distribution in the brain of mammals other than the rat, particularly in carnivores, is less well known than for other opiate peptides. In the present work, we have charted the distribution of -NE immunoreactive fibers and perikarya in the diencephalon and the brainstem of the dog. The highest densities of labeled fibers were found in the substantia nigra and in patches within the nucleus of the solitary tract. Moderate densities appeared in the arcuate nucleus (Ar), median eminence, entopeduncular nucleus, ventral tegmental area, retrorubral area, periaqueductal central gray, interpeduncular nucleus and lateral parabrachial nucleus. Groups of numerous labeled perikarya were localized in the magnocellular hypothalamic nuclei, Ar and in the central superior and incertus nuclei in the metencephalon. Moreover, less densely packed fibers and cells appeared widely distributed throughout many nuclei in the region studied. These results are discussed with regard to the pattern described in other species. In addition, the present results were compared with the distribution of met-enkephalin immunoreactivity in the diencephalon and the brainstem of the dog that we have recently described. Although the distributions of these two peptides overlap in many areas, the existence of numerous differences suggest that they form separate opiate systems in the dog.  相似文献   

11.
Metastin-like immunoreactivity in the rat medulla oblongata and spinal cord   总被引:1,自引:0,他引:1  
Metastin, the product of metastasis suppressor gene KiSS-1, is proposed to be the natural ligand for the G-protein-coupled receptor GPR54, known also as AXOR12. This immunohistochemical study, using a rabbit polyclonal antiserum against the human metastin fragment (45-54)-NH(2), showed that in rats metastin-like immunoreactivity (MTS-LI) was present in neurons of the nucleus of the solitary tract and caudoventrolateral reticular nucleus, and in cell processes of the spinal trigeminal tract and lateral reticular nucleus. MTS-LI was confined mainly to neurons and fibers at or caudal to the area postrema. In the spinal cord, MTS-LI cell processes formed a dense plexus in superficial layers I and II of the dorsal horn. The pattern of distribution of MTS-LI in the medulla and spinal cord suggests that this novel peptide may participate in autonomic and sensory neural signaling.  相似文献   

12.
The distribution and localization of neuromedin B, a novel bombesin-like decapeptide isolated from porcine spinal cord, was investigated by newly established radioimmunoassay and immunocytochemistry in the pig, cat and rat spinal cord. Neuromedin B-like immunoreactivity was found to be concentrated particularly in the dorsal part of lumbosacral segments in all species studied and the highest concentration of immunoreactivity was 25.7 +/- 3.4 pmol/g wet wt in the dorsal part of sacral region of pig spinal cord. The nature of the immunoreactivity was studied by gel permeation and high pressure liquid chromatography. Chromatography of spinal cord extracts from three species revealed two major peaks of neuromedin B-like immunoreactivity and the prevalent molecular from co-eluted with synthetic porcine neuromedin B. Immunocytochemistry localized neuromedin B immunoreactivity to fibres and terminals throughout the entire length of the spinal cord of pig, cat and rat. Fibres were most abundant in laminae I and II of the dorsal horn, the area around the central canal (lamina X) and intermediolateral cell columns of thoracic and sacral segments. In lumbosacral segments neuromedin B-immunoreactive fibres were slightly more numerous, in both dorsal and ventral spinal cord, than in cervical and thoracic regions.  相似文献   

13.
Rat bone marrow macrophage progenitor cells develop in vitro in the presence of rat embryo fibroblast conditioned medium into colonies and clusters. 1 alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) (0.12-12 nM) was found to enhance the formation of macrophage colonies and the proliferation of mononuclear phagocytes in liquid cultures of bone marrow cells (ED50 0.12-1.0 nM). Fractionation of bone marrow cells by centrifugal elutriation showed that: a) macrophage progenitors are heterogeneous in size; b) the progenitors eluted at early fractions have a lower proliferative capacity (form mainly small clusters) than those eluting at later fractions (higher counterflow velocities) which develop into macrophage colonies and c) that 1,25(OH)2D3 (at 12 nM) augments the expression of colony forming cells enriched in late eluting fractions while having a suppressive effect on expression of low proliferative potential cluster forming cells enriched in early eluting fractions. Dexamethasone was found to suppress the clonal growth of macrophage progenitor cells as well as their proliferation in liquid cultures (ED50 about 1 nM). Both dexamethasone and 1,25(OH)2D3 induced in mononuclear phagocytes of 4 d cultures an increased phagocytic capability. The data suggest a regulatory role for 1,25(OH)2D3 and glucocorticosteroids in myelopoietic processes in the rat. Furthermore, when compared with our recent findings with mouse bone marrow cells, the effects, their magnitude and concentration dependence imply genuine species differences in the responses of mice and rats to these hormones.  相似文献   

14.
Summary The development and closure of the neural folds was studied in C57BL/6J and loop-tail (Lp) mutant mice by means of scanning electron microscopy on a series of embryos ranging in age from 7.5 to 9.0 days of gestation. The normal embryos (C57BL/6J; +/+; Lp/+) showed a transitional zone of flattened cells lying between the surface ectoderm and neuroepithelial cells at the apices of the neural folds in the presumptive hindbrain and spinal cord, and ruffles occurred at the boundary between the flattened cells and surface ectoderm in regions of the folds which were about to fuse. In the abnormal loop-tail homozygotes (Lp/Lp) which exhibit dysraphism, the ruffles were arranged erratically along the zone of flattened cells. Moreover, at the stage when the folds became apposed and fused in the normal embryos, the abnormals showed ruffles extending the entire length of the unfused folds, thereby distinguishing the abnormals from retarded n normal embryos. Within the neural groove of the hindbrain region, the lateral neuroepithelial cells of the abnormal dysraphic embryos exhibited more flattened surfaces and fewer villous projections than in the normal embryos. The abnormal embryos also lagged behind their normal littermates in converting the body axis from the initial V-shape to the C-shaped configuration.This research was supported by NIH grant no. HD09562 from the National Institute of Child Health and Human Development, USPHS  相似文献   

15.
Despite a growing body of evidence that Vitamin D is involved in mammalian brain functioning, there has been a lack of direct evidence about its role in the human brain. This paper reports, for the first time, the distribution of the 1,25-dihydroxyvitamin D3 receptor (VDR), and 1alpha-hydroxylase (1alpha-OHase), the enzyme responsible for the formation of the active vitamin in the human brain. The receptor and the enzyme were found in both neurons and glial cells in a regional and layer-specific pattern. The VDR was restricted to the nucleus whilst 1alpha-OHase was distributed throughout the cytoplasm. The distribution of the VDR in human brain was strikingly similar to that reported in rodents. Many regions contained equivalent amounts of both the VDR and 1alpha-OHase, however the macrocellular cells within the nucleus basalis of Meynert (NBM) and the Purkinje cells in the cerebellum expressed 1alpha-OHase in the absence of VDR. The strongest immunohistochemical staining for both the receptor and enzyme was in the hypothalamus and in the large (presumably dopaminergic) neurons within the substantia nigra. The observed distribution of the VDR is consistent with the proposal that Vitamin D operates in a similar fashion to the known neurosteroids. The widespread distribution of 1alpha-OHase and the VDR suggests that Vitamin D may have autocrine/paracrine properties in the human brain.  相似文献   

16.
In recent years, receptors for calcitriol (the active form of vitamin D3) have been identified in monocytes and activated, but not resting, human B and T lymphocytes suggesting that it may be involved in immune regulation. Because lymphokines are central in the regulation and modulation of immune or inflammatory responses and since the calcium translocation is involved in the mitogen-induced activation of lymphocytes, we thought it interesting to study the role of calcitriol on interferon gamma (IFN-gamma) production in vitro. In this study, we report that calcitriol inhibits the IFN-gamma production by staphylococcal enterotoxin A-stimulated peripheral blood mononuclear cells (PBMC) in a dose-dependent fashion. The inhibitory effect was less potent in calcium ionophore A23187-stimulated PBMC and was absent in resting PBMC.  相似文献   

17.
目的:研究大鼠脊髓骶段(第2骶节)横断伤后5-羟色胺2A受体免疫反应(5-HT2AR-IR)的变化.方法:大鼠随机分为7组,即2h、8h和1d、2d、7d、30 d、60 d组,每组又随机分为手术组和假手术组.手术组在大鼠第2骶髓节段完全横断,假手术组只去除椎板,保留硬脊膜的完整,采用免疫荧光组织化学方法检测脊髓损伤下段5-HT2A-IR的变化.结果:2、8h手术组脊髓前角运动神经元区5-HT 2A-IR密度与假手术组比较无明显不同,1d后与假手术组比较开始增高,5-HT2A-IR密度随时间延长呈逐渐增加的趋势,直到手术后60 d达到最高水平.结论:慢性脊髓骶段完全横断后脊髓前角运动神经元的5-HT2A受体上调可能是5-羟色胺去神经支配后超敏感反应和痉挛发生的潜在机制.  相似文献   

18.
Summary Samples of CSF and plasma were obtained simultaneously from 46 adult patients who had no endocrine disorders and were undergoing routine diagnostic lumbar puncture because of suspected or proved prolapse of a disc. Concentrations of 25-OHD, 24,25(OH)2D and 1,25(OH)2D were measured. The samples were purified by column chromatography and fractionated by HPLC. In the appropriate fractions the vitamin D metabolites were measured by PBA, and cytoreceptor assay. The results were as follows (median, range in brackets): 25-OHD in CSF 8.3 ng/ml (2.0–24.8), in plasma 14.5 ng/ml (7.0–36.0). 24,25(OH)2D in CSF 1.8 ng/ml (0.3–4.6) and 2.5 ng/ml (0.4–4.7) in plasma. 1.25(OH)2 D in CSF 25.0 pg/ml (2.2–39.0) and 31.0 pg/ml (10.1–55.0) in plasma. The correlations between plasma and CSF concentrations were as follows: 25-OHDr=0.479 (P<0.001); 24,25(OH)2Dr=0.815 (P<0.001) and for 1.25(OH)2Dr=0.497 (P<0.001).Our findings showed vitamin D metabolites to be present in human CSF.Abbreviations Ca Calcium - CSF Cerebrospinal fluid - Vitamin D3 Cholecalciferol - CPM Counts per min - 24, 25 (OH)2D 24, 25-dihydroxyvitamin D3 - 1,25(OH)2D 1,25-dihydroxyvitamin D3 - Vitamin D2 Ergocalciferol - HPLC High-pressure liquid chromatography - 25OHD 25-hydroxyvitamin D3 - PTH Parathyroid hormone - PBA Protein binding assay - RIA Radioimmunoassay - D-CaBP Vitamin D dependent calcium-binding protein  相似文献   

19.
20.
Morphine and other opioids have direct analgesic actions in the spinal cord and chronic spinal administration of opioid agonists is used clinically in patients suffering from severe, chronic pain. Neuropathic pain resulting from peripheral nerve injury is often less sensitive to opioid therapy than other forms of chronic pain in both humans and animal models. Changes in spinal mu-opioid receptor (MOR) expression have been demonstrated in animal models of neuropathic pain. However, these changes alone fail to account for the attenuation of opioid activity. Reduced expression of delta-opioid receptors (DOR) following peripheral nerve injury has been reported but most of these reports are limited to subjective observation. The magnitude and consistency of these changes is therefore unclear. In addition, previous studies did not evaluate the effects of nerve injury on behavioral measures to confirm induction of aberrant pain symptoms. We therefore performed quantitative image analysis to evaluate the effect of peripheral nerve injury on DOR-immunoreactivity in spinal cord sections from rats previously characterized for sensory responsiveness. We observed statistically significant decreases ipsilateral to nerve injury in all three models tested: sciatic nerve transection, chronic constriction injury of the sciatic nerve and L5/L6 spinal nerve ligation. These results suggest that decreases in the expression of DOR are a common feature of peripheral nerve injury.  相似文献   

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