OBJECTIVE: To determine the effect of the area postrema (AP) of the medulla oblongata on gastrointestinal interdigestive migrating motor complex (MMC) and the plasma motilin level. METHODS: Interdigestive MMC activiti...OBJECTIVE: To determine the effect of the area postrema (AP) of the medulla oblongata on gastrointestinal interdigestive migrating motor complex (MMC) and the plasma motilin level. METHODS: Interdigestive MMC activities of the antrum and duodenum were recorded by strain gauge implanted on the serosa of 8 conscious dogs. A cannula was intubated in femoral vein for motilin injection. The plasma motilin concentration was measured by RIA. We observed: (1) normal interdigestive MMC activity and fluctuations in plasma motilin concentration; (2) the effects of electrically damaging the AP on MMC activity and plasma motilin level; (3) whether intravenous injection of motilin could induce phase III contractions after the AP was destroyed. RESULTS: (1) Typical interdigestive MMC with phase I, II, III, and IV was recorded in normal dogs. Phase III was concurrent with the peak of plasma motilin level. (2) In damaged AP dogs, antroduodenal interdigestive MMC contractions were suppressed; cyclic, phasic and migratory pattern of MMC was disrupted. Plasma motilin concentration was decreased. Intravenous injection of motilin could not induce phase III contractions. CONCLUSIONS: The area postrema might play an important role, which is mediated by motilin, on the regulation of interdigestive MMC.展开更多
Since 1990, a series of studies on rats, monkeys and human foetus showed that an arcshaped zone is present in the middle-caudal segment of medulla oblongata, running from the dorsomedial part to the ventrolateral part...Since 1990, a series of studies on rats, monkeys and human foetus showed that an arcshaped zone is present in the middle-caudal segment of medulla oblongata, running from the dorsomedial part to the ventrolateral part and passing through the reticular formation. It was named the medullary visceral zone (MVZ). The MVZ has been investigated with various techniques (Golgi method, Nissl method, immunohistochemical method, in situ hybridization method, triple labelling method, neurophysiological method, etc. ), and the morphological features as well as the physiological functions of MVZ have been preliminarily understood. It is proved that the medullary life center is located in MVZ.An introduction and some comments are given on the location of MVZ, its shape and extent, cytoarchitecture, and chemicoarchitecture, afferent and efferent fiber connections and their functions, and its important physiological functions.展开更多
Objective Despite accumulating evidence on a role of immune cells and their associated chemicals in mecha- nisms of pain, few studies have addressed the potential role of chemokines in the descending facilitation of p...Objective Despite accumulating evidence on a role of immune cells and their associated chemicals in mecha- nisms of pain, few studies have addressed the potential role of chemokines in the descending facilitation of persistent pain. The present study was undertaken to test the hypothesis that the chemokine （C-C motif） ligand 2 （CCL2） （commonly known as monocyte chemoattractant protein-1） signaling in the rostral ventromedial medulla （RVM）, a pivotal structure in brainstem pain modulatory circuitry, is involved in descending pain facilitation in rats. Methods An L5 spinal nerve ligation （SNL） was produced in rats under pentobarbital anesthesia. Western blot and immunohistochemistry were used to detect the expression levels of CCL2 and CCL2 receptor （CCR2）, and examine their distributions compared with the neuronal marker NeuN as well as glial markers glial fibrillary acidic protein （GFAP, astroglial） and CD 11 b （microglial）, respectively. Results SNL induced an increase in CCL2 expression in the RVM, and this returned to the control level at 4 weeks after injury. The induced CCL2 colocalized with NeuN, but not with GFAP and CD1 lb. CCR2 was also upregu- lated by SNL in the RVM, and this increase lasted for at least 4 weeks. CCR2 was colocalized with CD1 lb but not GFAP. Few RVM neurons also exhibited CCR2 staining. Neutralizing CCL2 with an anti-CCL2 antibody （0.2-20 ng） or injecting RS-102895 （0.1-10 pmol）, a CCR2b chemokine receptor antagonist, into the RVM on day 1 after SNL, significantly at- tenuated the established thermal and mechanical hypersensitivity. In addition, injection of recombinant rat CCL2 （0.03-3 pmol） into the RVM induced dose-dependent hyperalgesia, which was prevented by pretreatment with RS-102895 （10 pmol）. Interleukin-β （IL-1]3）, a potent inducer of neuronal CCL2, was also selectively upregulated in RVM reactive as- trocytes. Injection of IL-1 ]3 （120 fmol） into the RVM induced behavioral hyperalgesia, which was blocked by RS-102895展开更多
The rostral ventromedial medulla （RVM） is a prominent component of the descending modulatory system involved in the control of spinal nociceptive transmission. In the current study, we investigated melanocortin-4 re...The rostral ventromedial medulla （RVM） is a prominent component of the descending modulatory system involved in the control of spinal nociceptive transmission. In the current study, we investigated melanocortin-4 receptor （MC4R） expression in the RVM, where the neurons involved in modulation of nociception reside. Using a line of mice expressing green fluorescent protein （GFP） under the control of the MC4R promoter, we found a large number of GFP-positive neurons in the RVM [nucleus raphe magnus （NRM） and nucleus gigantocellularis pars a （NGCa）]. Fluorescence immunohisto- chemistry revealed that approximately 10% of MC4R-GFP-positive neurons coexpressed tyrosine hydroxylase, indicating that they were catecholaminergic, whereas 50%-75% of those coexpressed tryp- tophan hydroxylase, indicating that they were serotonergic. Our findings support the hypothesis that MC4R signaling in RVM may modulate the activity of serotonergic sympathetic outflow sensitive to nociceptive signals, and that MC4R signaling in RVM may contribute to the descending modulation of nociceptive transmission.展开更多
Background Airway symptoms in asthma are related to decrease of epinephrine secretion, which may be ascribed to elevated nerve growth factor （NGF） in the organism. The aim of this study was to monitor the neuroendoc...Background Airway symptoms in asthma are related to decrease of epinephrine secretion, which may be ascribed to elevated nerve growth factor （NGF） in the organism. The aim of this study was to monitor the neuroendocrine alteration in the adrenal medulla of asthmatic rats. Methods Sixteen rats were randomly divided into two groups （n=-8）, control group and asthma group, and the asthmatic rats were sensitized and challenged with ovalbumin （OVA）. The levels of NGF, epinephrine and norepinephrine in serum were detected by enzyme linked immunosorbent assay （ELISA）, the NGF expression in adrenal medulla was detected by immunohistochemistry, and the changes in the ultrastructure of the adrenal medulla was observed by electron microscopy. Results The NGF expression was increased in asthmatic rats compared with control rats. Compared with control rats, the results indicated that the epinephrine level was decreased in asthmatic rats, but no significant difference was found in norepinephrine levels. We found more ganglion cells in the adrenal medulla of asthmatic rats than in control rats, with NGF immunostaining mainly located in these ganglion cells. Electron microscopic images showed the density of chromaffin granula decreased and there was shrunken nucleolemma in the adrenal medullary cells of asthmatic rats. Conclusion The innervation of the adrenal medulla is changed in asthmatic rats, and it may contribute to the epinephrine decrease in asthma.展开更多
BACKGROUND: Obstructive jaundice is a common disease. Acute renal injury, secondary to obstructive jaundice, is one of the main causes of postoperative multiple system failure. This investigation evaluated renal funct...BACKGROUND: Obstructive jaundice is a common disease. Acute renal injury, secondary to obstructive jaundice, is one of the main causes of postoperative multiple system failure. This investigation evaluated renal function and renal aquaporin 2 (AQP2) expression changes in obstructive jaundice. METHODS: Forty male Wistar rats were equally randomized into two groups. Twenty in the obstructive jaundice group were subjected to common bile duct ligation, and then were subdivided into 7- and 14-day obstruction groups, and the other 20 sham-operated rats were also subdivided into 7- and 14-day groups. At the end of each experiment, rats were sacrificed, venous blood was collected from the inferior vena cava, and serum creatinine and urine nitrogen concentrations were measured. At the same time, the medulla of the right kidney was separated and AQP2 expression was assessed. The RT-PCR technique was used to detect AQP2 mRNA expression. RESULTS: Ligation of the common bile duct caused significant rises in serum bilirubin, creatinine clearance and urine nitrogen. AQP2 expression in the medulla decreased mere significantly (38.35 +/- 2.08) in the 7-day ligation group than in the sham-operated group (41.06 +/- 1.04), as did that in the 14-day ligation group, even more than (31.89 +/- 1.57). The expression of AQP2 mRNA also decreased more significantly in the 14-day group (0.5429 +/- 0.1107) than in the 7-day group (0.6071 +/- 0.1328). CONCLUSION: AQP2 expression is inhibited in obstructive jaundice, and so is its gene expression.展开更多
Brain-controlled technology is the key technology in biological control,and the corresponding relationship between animal brain nuclei and motor behavior is the core.The purpose of this study was to explore the motor ...Brain-controlled technology is the key technology in biological control,and the corresponding relationship between animal brain nuclei and motor behavior is the core.The purpose of this study was to explore the motor nuclei of the medulla oblongata in carp.The carps were subjected to electrical stimulation and chemical stimulation experiments,respectively,in the water-free state,and the effective chemical stimulation sites were injected with the pontamine sky blue solution.The brain tissue sections were obtained by paraffin tissue section technology and the neutral red staining method.By comparing the positions of the brain nuclei shown in earlier studies,the motor nerve nuclei in the medulla oblongata were identified.The brain electrode was implanted into the motor nucleus of the medulla oblongata,and the underwater control experiment and behavioral tests were carried out with different electrical stimulation parameters.The results showed that the abducens nucleus(NVI)was the motor nucleus that controls the ipsilateral steering,and the facial nucleus(NVII)was the motor nucleus that controls the forward movement.By adjusting the stimulation voltage and the stimulation pulse number,the carp can be stably controlled to achieve a left–right steering motion of 30°–180°and a forward motion of more than 80 cm/s.This study indicated that the quantitative control of the steering and forward behavior of the carp can be achieved by electrical stimulation of the NVI and NVII,which provided a certain experimental basis for the accurate control of the carp robot.展开更多
Descending nociceptive modulation from the supraspinal structures plays an important role in cancer-induced bone pain (CIBP). Rostral ventromedial medulla (RVM) is a critical component of descending nociceptive facili...Descending nociceptive modulation from the supraspinal structures plays an important role in cancer-induced bone pain (CIBP). Rostral ventromedial medulla (RVM) is a critical component of descending nociceptive facilitation circuitry, but so far the mechanisms are poorly known. In this study, we investigated the role of RVM glial activation in the descending nociceptive facilitation circuitry in a CIBP rat model. CIBP rats showed significant activation of microglia and astrocytes, and also up-regulation of phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) and pro-inflammatory mediators released by glial cells (IL-1β, IL-6, TNF-α and brain-derived neurotrophic factor) in the RVM. Stereotaxic microinjection of the glial inhibitors (minocycline and fluorocitrate) into CIBP rats’ RVM could reverse the glial activation and significantly attenuate mechanical allodynia in a time-dependent manner. RVM microinjection of p38 MAPK inhibitor (SB203580) abolished the activation of microglia, reversed the associated up-regulation of proinflammatory mediators and significantly attenuated mechanical allodynia. Taken together, these results suggest that RVM glial activation is involved in the pathogenesis of CIBP. RVM microglial p38 MAPK signaling pathway is activated and leads to the release of downstream pro-inflammatory mediators, which contribute to the descending facilitation of CIBP.展开更多
The parabrachial nucleus(PBN)integrates interoceptive and exteroceptive information to control various behavioral and physiological processes including breathing,emotion,and sleep/wake regulation through the neural ci...The parabrachial nucleus(PBN)integrates interoceptive and exteroceptive information to control various behavioral and physiological processes including breathing,emotion,and sleep/wake regulation through the neural circuits that connect to the forebrain and the brainstem.However,the precise identity and function of distinct PBN subpopulations are still largely unknown.Here,we leveraged molecular characterization,retrograde tracing,optogenetics,chemogenetics,and electrocortical recording approaches to identify a small subpopulation of neurotensin-expressing neurons in the PBN that largely project to the emotional control regions in the forebrain,rather than the medulla.Their activation induces freezing and anxiety-like behaviors,which in turn result in tachypnea.In addition,optogenetic and chemogenetic manipulations of these neurons revealed their function in promoting wakefulness and maintaining sleep architecture.We propose that these neurons comprise a PBN subpopulation with specific gene expression,connectivity,and function,which play essential roles in behavioral and physiological regulation.展开更多
基金supported by the National Climbing Program (No．95-Ⅷ-19-222)； the National Natural science Foundation of China(No．39770285)
文摘OBJECTIVE: To determine the effect of the area postrema (AP) of the medulla oblongata on gastrointestinal interdigestive migrating motor complex (MMC) and the plasma motilin level. METHODS: Interdigestive MMC activities of the antrum and duodenum were recorded by strain gauge implanted on the serosa of 8 conscious dogs. A cannula was intubated in femoral vein for motilin injection. The plasma motilin concentration was measured by RIA. We observed: (1) normal interdigestive MMC activity and fluctuations in plasma motilin concentration; (2) the effects of electrically damaging the AP on MMC activity and plasma motilin level; (3) whether intravenous injection of motilin could induce phase III contractions after the AP was destroyed. RESULTS: (1) Typical interdigestive MMC with phase I, II, III, and IV was recorded in normal dogs. Phase III was concurrent with the peak of plasma motilin level. (2) In damaged AP dogs, antroduodenal interdigestive MMC contractions were suppressed; cyclic, phasic and migratory pattern of MMC was disrupted. Plasma motilin concentration was decreased. Intravenous injection of motilin could not induce phase III contractions. CONCLUSIONS: The area postrema might play an important role, which is mediated by motilin, on the regulation of interdigestive MMC.
文摘Since 1990, a series of studies on rats, monkeys and human foetus showed that an arcshaped zone is present in the middle-caudal segment of medulla oblongata, running from the dorsomedial part to the ventrolateral part and passing through the reticular formation. It was named the medullary visceral zone (MVZ). The MVZ has been investigated with various techniques (Golgi method, Nissl method, immunohistochemical method, in situ hybridization method, triple labelling method, neurophysiological method, etc. ), and the morphological features as well as the physiological functions of MVZ have been preliminarily understood. It is proved that the medullary life center is located in MVZ.An introduction and some comments are given on the location of MVZ, its shape and extent, cytoarchitecture, and chemicoarchitecture, afferent and efferent fiber connections and their functions, and its important physiological functions.
基金supported by grants from the National Institutes of Health (NS059028,NS060735, DE011964, DE021804, and DE018573)
文摘Objective Despite accumulating evidence on a role of immune cells and their associated chemicals in mecha- nisms of pain, few studies have addressed the potential role of chemokines in the descending facilitation of persistent pain. The present study was undertaken to test the hypothesis that the chemokine （C-C motif） ligand 2 （CCL2） （commonly known as monocyte chemoattractant protein-1） signaling in the rostral ventromedial medulla （RVM）, a pivotal structure in brainstem pain modulatory circuitry, is involved in descending pain facilitation in rats. Methods An L5 spinal nerve ligation （SNL） was produced in rats under pentobarbital anesthesia. Western blot and immunohistochemistry were used to detect the expression levels of CCL2 and CCL2 receptor （CCR2）, and examine their distributions compared with the neuronal marker NeuN as well as glial markers glial fibrillary acidic protein （GFAP, astroglial） and CD 11 b （microglial）, respectively. Results SNL induced an increase in CCL2 expression in the RVM, and this returned to the control level at 4 weeks after injury. The induced CCL2 colocalized with NeuN, but not with GFAP and CD1 lb. CCR2 was also upregu- lated by SNL in the RVM, and this increase lasted for at least 4 weeks. CCR2 was colocalized with CD1 lb but not GFAP. Few RVM neurons also exhibited CCR2 staining. Neutralizing CCL2 with an anti-CCL2 antibody （0.2-20 ng） or injecting RS-102895 （0.1-10 pmol）, a CCR2b chemokine receptor antagonist, into the RVM on day 1 after SNL, significantly at- tenuated the established thermal and mechanical hypersensitivity. In addition, injection of recombinant rat CCL2 （0.03-3 pmol） into the RVM induced dose-dependent hyperalgesia, which was prevented by pretreatment with RS-102895 （10 pmol）. Interleukin-β （IL-1]3）, a potent inducer of neuronal CCL2, was also selectively upregulated in RVM reactive as- trocytes. Injection of IL-1 ]3 （120 fmol） into the RVM induced behavioral hyperalgesia, which was blocked by RS-102895
基金supported by grants from National Natural Science Foundation of China(No.81071307,No.81271766,and No.81673964)Special Fund of Fundamental Scientific Research Business Expense for Higher School of Central Government(No.2012TS060)
文摘The rostral ventromedial medulla （RVM） is a prominent component of the descending modulatory system involved in the control of spinal nociceptive transmission. In the current study, we investigated melanocortin-4 receptor （MC4R） expression in the RVM, where the neurons involved in modulation of nociception reside. Using a line of mice expressing green fluorescent protein （GFP） under the control of the MC4R promoter, we found a large number of GFP-positive neurons in the RVM [nucleus raphe magnus （NRM） and nucleus gigantocellularis pars a （NGCa）]. Fluorescence immunohisto- chemistry revealed that approximately 10% of MC4R-GFP-positive neurons coexpressed tyrosine hydroxylase, indicating that they were catecholaminergic, whereas 50%-75% of those coexpressed tryp- tophan hydroxylase, indicating that they were serotonergic. Our findings support the hypothesis that MC4R signaling in RVM may modulate the activity of serotonergic sympathetic outflow sensitive to nociceptive signals, and that MC4R signaling in RVM may contribute to the descending modulation of nociceptive transmission.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 30570802, No. 30800502 and No. 30801505）.
文摘Background Airway symptoms in asthma are related to decrease of epinephrine secretion, which may be ascribed to elevated nerve growth factor （NGF） in the organism. The aim of this study was to monitor the neuroendocrine alteration in the adrenal medulla of asthmatic rats. Methods Sixteen rats were randomly divided into two groups （n=-8）, control group and asthma group, and the asthmatic rats were sensitized and challenged with ovalbumin （OVA）. The levels of NGF, epinephrine and norepinephrine in serum were detected by enzyme linked immunosorbent assay （ELISA）, the NGF expression in adrenal medulla was detected by immunohistochemistry, and the changes in the ultrastructure of the adrenal medulla was observed by electron microscopy. Results The NGF expression was increased in asthmatic rats compared with control rats. Compared with control rats, the results indicated that the epinephrine level was decreased in asthmatic rats, but no significant difference was found in norepinephrine levels. We found more ganglion cells in the adrenal medulla of asthmatic rats than in control rats, with NGF immunostaining mainly located in these ganglion cells. Electron microscopic images showed the density of chromaffin granula decreased and there was shrunken nucleolemma in the adrenal medullary cells of asthmatic rats. Conclusion The innervation of the adrenal medulla is changed in asthmatic rats, and it may contribute to the epinephrine decrease in asthma.
基金This study was supported by a grant from the Liaoning Province Research Project for Institution of Higher Education (2004D282).
文摘BACKGROUND: Obstructive jaundice is a common disease. Acute renal injury, secondary to obstructive jaundice, is one of the main causes of postoperative multiple system failure. This investigation evaluated renal function and renal aquaporin 2 (AQP2) expression changes in obstructive jaundice. METHODS: Forty male Wistar rats were equally randomized into two groups. Twenty in the obstructive jaundice group were subjected to common bile duct ligation, and then were subdivided into 7- and 14-day obstruction groups, and the other 20 sham-operated rats were also subdivided into 7- and 14-day groups. At the end of each experiment, rats were sacrificed, venous blood was collected from the inferior vena cava, and serum creatinine and urine nitrogen concentrations were measured. At the same time, the medulla of the right kidney was separated and AQP2 expression was assessed. The RT-PCR technique was used to detect AQP2 mRNA expression. RESULTS: Ligation of the common bile duct caused significant rises in serum bilirubin, creatinine clearance and urine nitrogen. AQP2 expression in the medulla decreased mere significantly (38.35 +/- 2.08) in the 7-day ligation group than in the sham-operated group (41.06 +/- 1.04), as did that in the 14-day ligation group, even more than (31.89 +/- 1.57). The expression of AQP2 mRNA also decreased more significantly in the 14-day group (0.5429 +/- 0.1107) than in the 7-day group (0.6071 +/- 0.1328). CONCLUSION: AQP2 expression is inhibited in obstructive jaundice, and so is its gene expression.
基金supported by the Project of National Natural Science Foundation of China(project number:61573305)Project of Natural Science Foundation of Hebei Province of China(project number:F2022203038,F2019203511)National High-Tech Research and Development Plan of China(863 Plan)Project(2013AA****)Fund.
文摘Brain-controlled technology is the key technology in biological control,and the corresponding relationship between animal brain nuclei and motor behavior is the core.The purpose of this study was to explore the motor nuclei of the medulla oblongata in carp.The carps were subjected to electrical stimulation and chemical stimulation experiments,respectively,in the water-free state,and the effective chemical stimulation sites were injected with the pontamine sky blue solution.The brain tissue sections were obtained by paraffin tissue section technology and the neutral red staining method.By comparing the positions of the brain nuclei shown in earlier studies,the motor nerve nuclei in the medulla oblongata were identified.The brain electrode was implanted into the motor nucleus of the medulla oblongata,and the underwater control experiment and behavioral tests were carried out with different electrical stimulation parameters.The results showed that the abducens nucleus(NVI)was the motor nucleus that controls the ipsilateral steering,and the facial nucleus(NVII)was the motor nucleus that controls the forward movement.By adjusting the stimulation voltage and the stimulation pulse number,the carp can be stably controlled to achieve a left–right steering motion of 30°–180°and a forward motion of more than 80 cm/s.This study indicated that the quantitative control of the steering and forward behavior of the carp can be achieved by electrical stimulation of the NVI and NVII,which provided a certain experimental basis for the accurate control of the carp robot.
基金supported by grants from the National Natural Science Foundation of China(No.30901396,No.81070890,No.30872441and No.81171259)
文摘Descending nociceptive modulation from the supraspinal structures plays an important role in cancer-induced bone pain (CIBP). Rostral ventromedial medulla (RVM) is a critical component of descending nociceptive facilitation circuitry, but so far the mechanisms are poorly known. In this study, we investigated the role of RVM glial activation in the descending nociceptive facilitation circuitry in a CIBP rat model. CIBP rats showed significant activation of microglia and astrocytes, and also up-regulation of phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) and pro-inflammatory mediators released by glial cells (IL-1β, IL-6, TNF-α and brain-derived neurotrophic factor) in the RVM. Stereotaxic microinjection of the glial inhibitors (minocycline and fluorocitrate) into CIBP rats’ RVM could reverse the glial activation and significantly attenuate mechanical allodynia in a time-dependent manner. RVM microinjection of p38 MAPK inhibitor (SB203580) abolished the activation of microglia, reversed the associated up-regulation of proinflammatory mediators and significantly attenuated mechanical allodynia. Taken together, these results suggest that RVM glial activation is involved in the pathogenesis of CIBP. RVM microglial p38 MAPK signaling pathway is activated and leads to the release of downstream pro-inflammatory mediators, which contribute to the descending facilitation of CIBP.
基金supported by the University of Michigan startup funds and the NIH Grants R01 AT011652 and R01 HL156989.
文摘The parabrachial nucleus(PBN)integrates interoceptive and exteroceptive information to control various behavioral and physiological processes including breathing,emotion,and sleep/wake regulation through the neural circuits that connect to the forebrain and the brainstem.However,the precise identity and function of distinct PBN subpopulations are still largely unknown.Here,we leveraged molecular characterization,retrograde tracing,optogenetics,chemogenetics,and electrocortical recording approaches to identify a small subpopulation of neurotensin-expressing neurons in the PBN that largely project to the emotional control regions in the forebrain,rather than the medulla.Their activation induces freezing and anxiety-like behaviors,which in turn result in tachypnea.In addition,optogenetic and chemogenetic manipulations of these neurons revealed their function in promoting wakefulness and maintaining sleep architecture.We propose that these neurons comprise a PBN subpopulation with specific gene expression,connectivity,and function,which play essential roles in behavioral and physiological regulation.
