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1.
Exp Cell Res ; 418(1): 113224, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35643178

RESUMO

PURPOSE: Acute respiratory distress syndrome (ARDS), a severe medical condition, is among the major causes of death in critically ill patients. Morphine is used as a therapeutic agent against severe pain. The mechanisms of its reactions over ARDS are not fully understood. The aim of this study was to assess the mechanism of morphine in rats with ARDS. METHODS: Rats were injected with lipopolysaccharide to induce ARDS, and some rats were pre-treated with graded doses of morphine in the lateral ventricles to assess survival and non-infected mortality. Immunohistochemical and HE staining were performed to measure MPO and CD68 activity in the lungs and lung injury. ELISA was conducted to detect the inflammatory factor levels in the plasma and BALF. Co-labeling of µ-opioid receptor (MOR) and c-Fos was observed in the brain tissues. MOR-positive cells in brain tissues were evaluated using immunohistochemistry. The effect of MOR antagonists on ARDS was examined in rats by pre-injection of naloxone or methylnaltrexone. The expression of MyD88, TLR4, and NF-κB was lastly assessed. RESULTS: Dose-independent improvement was observed in respiratory capacity and lung injury in ARDS rats after morphine pre-injection, along with reduced inflammatory factors in the plasma and BALF. MOR-positive cells were elevated after morphine, which occurred within the ventral part of the gigantocellular reticular nucleus (GiV). Naloxone and methylnaltrexone blocked the effects of morphine via central and peripheral MOR. Morphine activated TLR pathway in a MyD88-dependent manner. CONCLUSION: Morphine activates MOR within the GiV and the TLR pathway to attenuate ARDS in rats.


Assuntos
Lesão Pulmonar , Síndrome do Desconforto Respiratório , Animais , Lipopolissacarídeos , Morfina/farmacologia , Fator 88 de Diferenciação Mieloide , Naloxona/farmacologia , Ratos , Receptores Opioides , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/tratamento farmacológico
2.
Neurochem Res ; 44(4): 968-977, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30758814

RESUMO

The aim of the study was to examine the Braak's hypothesis to explain the spreading and distribution of the neuropathological changes observed in the course of Parkinson's disease among ascending neuroanatomical regions. We investigated the neurotransmitter levels (monoamines and amino acid concentration) as well as tyrosine hydroxylase (TH) and transglutaminase-2 (TG2) mRNA expression in the mouse striata (ST) after intracerebral α-synuclein (ASN) administration into gigantocellular reticular nucleus (Gi). Male C57BL/10 Tar mice were used in this study. ASN was administrated by stereotactic injection into Gi area (4 µl; 1 µg/µl) and mice were decapitated after 1, 4 or 12 weeks post injection. The neurotransmitters concentration in ST were evaluated using HPLC detection. TH and TG2 mRNA expression were examined by Real-Time PCR method. At 4 and 12 weeks after ASN administration we observed decrease of DA concentration in ST relative to control groups and we found a significantly higher concentration one of the DA metabolites-DOPAC. At these time points, we also noticed the increase in DA turnover determined as DOPAC/DA ratio. Additionally, at 4 and 12 weeks after ASN injection we noted decreasing of TH mRNA expression. Our findings corresponds with the Braak's theory about the presence of the first neuropathological changes within brainstem and then with time affecting higher neuroanatomical regions. These results obtained after administration of ASN monomers to the Gi area may be useful to explain the pathogenesis of Parkinson's disease.


Assuntos
Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Formação Reticular/efeitos dos fármacos , Formação Reticular/metabolismo , Transmissão Sináptica/efeitos dos fármacos , alfa-Sinucleína/administração & dosagem , Animais , Injeções Intravenosas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transmissão Sináptica/fisiologia
3.
Am J Physiol Endocrinol Metab ; 309(8): E759-66, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26330345

RESUMO

Although central PYY delivery potently increases food intake, the sites of action and mechanisms mediating these hyperphagic effects are not fully understood. The present studies investigate the contribution of lateral parabrachial nucleus (lPBN) PYY-Y receptor signaling to food intake control, as lPBN neurons express Y receptors and receive PYY fibers and are known to integrate circulating and visceral sensory signals to regulate energy balance. Immunohistochemical results identified a subpopulation of gigantocellular reticular nucleus PYY-producing neurons that project monosynaptically to the lPBN, providing an endogenous source of PYY to the lPBN. lPBN microinjection of PYY-(1-36) or PYY-(3-36) markedly increased food intake by increasing meal size. To determine which receptors mediate these behavioral results, we first performed quantitative real-time PCR to examine the relative levels of Y receptor expression in lPBN tissue. Gene expression analyses revealed that, while Y1, Y2, and Y5 receptors are each expressed in lPBN tissue, Y1 receptor mRNA is expressed at fivefold higher levels than the others. Furthermore, behavioral/pharmacological results demonstrated that the hyperphagic effects of PYY-(3-36) were eliminated by lPBN pretreatment with a selective Y1 receptor antagonist. Together, these results highlight the lPBN as a novel site of action for the intake-stimulatory effects of central PYY-Y1 receptor signaling.


Assuntos
Comportamento Alimentar/fisiologia , Núcleos Parabraquiais/metabolismo , Fragmentos de Peptídeos/metabolismo , Peptídeo YY/metabolismo , RNA Mensageiro/metabolismo , Receptores de Neuropeptídeo Y/genética , Animais , Comportamento Alimentar/efeitos dos fármacos , Masculino , Microinjeções , Núcleos Parabraquiais/efeitos dos fármacos , Núcleos Parabraquiais/fisiologia , Fragmentos de Peptídeos/farmacologia , Peptídeo YY/farmacologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Neuropeptídeo Y/efeitos dos fármacos , Receptores de Neuropeptídeo Y/metabolismo
4.
J Oral Biosci ; 66(1): 134-144, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37952729

RESUMO

OBJECTIVES: The gigantocellular reticular nucleus (Gi) projects to the nuclues of the solitary tract nucleus (NTS) and the lateral reticular formation (LRF) above the nucleus ambiguus. The swallowing central pattern generator comprises the NTS and the LRF. The present study examined whether stimulation of the Gi affects the swallowing reflex. METHODS: Experiments were performed on urethane-anesthetized rats. The swallowing reflex was evoked by repetitive electrical stimulation of the superior laryngeal nerve and responses were recorded from the mylohyoid muscle on an electromyogram. The Gi was stimulated electrically. In addition, glutamate was injected into the Gi. The Friedman's test, followed by the Wilcoxon signed-rank test with Bonferroni correction, were used to assess the effects of electrical stimulation of the Gi. The Wilcoxon signed-rank test was used to assess the effects of glutamate injection into the Gi. Differences were considered significant at the P < 0.05 level. RESULTS: The number of swallows was significantly increased or decreased by electrical stimulation of the Gi or after injection of glutamate into the Gi. In both electrical stimulation of the Gi and injection of glutamate into the Gi, the onset latency of the first swallow was prolonged when the number of swallows was decreased but showed no change when the number of swallows was increased. CONCLUSIONS: The present results suggest that the Gi is involved in the control of swallowing.


Assuntos
Deglutição , Núcleo Solitário , Ratos , Animais , Ratos Sprague-Dawley , Deglutição/fisiologia , Ácido Glutâmico/farmacologia , Formação Reticular , Reflexo/fisiologia
5.
Int J Nanomedicine ; 19: 7473-7492, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39071504

RESUMO

Background: Gigantocellular reticular nucleus (GRNs) executes a vital role in locomotor recovery after spinal cord injury. However, due to its unique anatomical location deep within the brainstem, intervening in GRNs for spinal cord injury research is challenging. To address this problem, this study adopted an extracorporeal magnetic stimulation system to observe the effects of selective magnetic stimulation of GRNs with iron oxide nanoparticles combined treadmill training on locomotor recovery after spinal cord injury, and explored the possible mechanisms. Methods: Superparamagnetic iron oxide (SPIO) nanoparticles were stereotactically injected into bilateral GRNs of mice with moderate T10 spinal cord contusion. Eight-week selective magnetic stimulation produced by extracorporeal magnetic stimulation system (MSS) combined with treadmill training was adopted for the animals from one week after surgery. Locomotor function of mice was evaluated by the Basso Mouse Scale, Grid-walking test and Treadscan analysis. Brain MRI, anterograde virus tracer and immunofluorescence staining were applied to observe the tissue compatibility of SPIO in GRNs, trace GRNs' projections and evaluate neurotransmitters' expression in spinal cord respectively. Motor-evoked potentials and H reflex were collected for assessing the integrity of cortical spinal tract and the excitation of motor neurons in anterior horn. Results: (1) SPIO persisted in GRNs for a minimum of 24 weeks without inducing apoptosis of GRN cells, and degraded slowly over time. (2) MSS-enabled treadmill training dramatically improved locomotor performances of injured mice, and promoted cortico-reticulo-spinal circuit reorganization. (3) MSS-enabled treadmill training took superimposed roles through both activating GRNs to drive more projections of GRNs across lesion site and rebalancing neurotransmitters' expression in anterior horn of lumbar spinal cord. Conclusion: These results indicate that selective MSS intervention of GRNs potentially serves as an innovative strategy to promote more spared fibers of GRNs across lesion site and rebalance neurotransmitters' expression after spinal cord injury, paving the way for the structural remodeling of neural systems collaborating with exercise training, thus ultimately contributing to the reconstruction of cortico-reticulo-spinal circuit.


Assuntos
Nanopartículas Magnéticas de Óxido de Ferro , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/fisiopatologia , Nanopartículas Magnéticas de Óxido de Ferro/química , Camundongos , Locomoção/fisiologia , Recuperação de Função Fisiológica/fisiologia , Medula Espinal , Condicionamento Físico Animal , Formação Reticular , Magnetoterapia/métodos , Camundongos Endogâmicos C57BL , Feminino , Potencial Evocado Motor/fisiologia
6.
Neurosci Lett ; 733: 135088, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32464262

RESUMO

Orexin/hypocretin has been implicated in central motor control. The gigantocellular reticular nucleus (Gi), a key element of the brainstem motor inhibitory system, also receives orexinergic innervations. However, the modulations of orexin on the neuronal activities and the underlying cellular mechanisms in Gi neurons remain unknown. Here, through whole-cell patch-clamp recordings, we first observed that orexin increased the firing frequency in Gi neurons. Interestingly, a postsynaptic depolarization elicited by orexin was observed in the presence of tetrodotoxin, without altering the input resistance of Gi neurons at around -60 mV. Moreover, through comparing the current-frequency curves constructed by identical current injections from equal membrane potentials, we found that orexin also increased the repetitive firing ability of Gi neurons. This action appeared to be caused by the shortening of inter-spike intervals, without altering the waveform of individual action potentials. We finally revealed that activation of the non-selective cationic conductance contributed to the orexin-elicited excitation in Gi neurons. Together, these results suggest that orexin may facilitate Gi-mediated motor functions through enhancing the neuronal activities of Gi neurons.


Assuntos
Neurônios/metabolismo , Orexinas/metabolismo , Formação Reticular/metabolismo , Potenciais de Ação/fisiologia , Animais , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley
7.
Neurosci Lett ; 653: 146-151, 2017 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-28549933

RESUMO

Previous studies have revealed that orexin may actively participate in central motor control. The gigantocellular reticular nucleus (Gi) is a key element of the brainstem motor inhibitory system. The descending orexinergic projections also reach Gi region, and microinjection of orexin into Gi causes robust muscle tone inhibition. However, the modulation effects of orexin on Gi neurons remain unclear. In the present study, using whole-cell patch-clamp recordings, we initially observed that orexin elicited an inward current in Gi neurons at a holding potential of -70mV in a concentration-dependent manner. By combining electrophysiology with neuropharmacological methods, we further determined that the orexin-induced inward current was directly mediated by the activation of postsynaptic orexin-1 and orexin-2 receptors. Moreover, orexin did not affect the frequency and amplitude of miniature excitatory and inhibitory postsynaptic currents in Gi neurons, which suggests that orexin had no effects on neurotransmission to these neurons. Therefore, the direct excitatory effect of orexin on an inhibitory motor structure, the Gi, was reported in the present study. This modulation may be integrated into the role of orexin in central motor control.


Assuntos
Neurônios/fisiologia , Receptores de Orexina/fisiologia , Orexinas/fisiologia , Formação Reticular/fisiologia , Animais , Orexinas/administração & dosagem , Ratos Sprague-Dawley , Sinapses/fisiologia , Potenciais Sinápticos
8.
Brain Struct Funct ; 221(3): 1623-33, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25633472

RESUMO

The present study investigated the projections of the gigantocellular reticular nucleus (Gi) and its neighbors--the dorsal paragigantocellular reticular nucleus (DPGi), the alpha/ventral part of the gigantocellular reticular nucleus (GiA/V), and the lateral paragigantocellular reticular nucleus (LPGi)--to the mouse spinal cord by injecting the anterograde tracer biotinylated dextran amine (BDA) into the Gi, DPGi, GiA/GiV, and LPGi. The Gi projected to the entire spinal cord bilaterally with an ipsilateral predominance. Its fibers traveled in both the ventral and lateral funiculi with a greater presence in the ventral funiculus. As the fibers descended in the spinal cord, their density in the lateral funiculus increased. The terminals were present mainly in laminae 7-10 with a dorsolateral expansion caudally. In the lumbar and sacral cord, a considerable number of terminals were also present in laminae 5 and 6. Contralateral fibers shared a similar pattern to their ipsilateral counterparts and some fibers were seen to cross the midline. Fibers arising from the DPGi were similarly distributed in the spinal cord except that there was no dorsolateral expansion in the lumbar and sacral segments and there were fewer fiber terminals. Fibers arising from GiA/V predominantly traveled in the ventral and lateral funiculi ipsilaterally. Ipsilaterally, the density of fibers in the ventral funiculus decreased along the rostrocaudal axis, whereas the density of fibers in the lateral funiculus increased. They terminate mainly in the medial ventral horn and lamina 10 with a smaller number of fibers in the dorsal horn. Fibers arising from the LPGi traveled in both the ventral and lateral funiculi and the density of these fibers in the ventral and lateral funiculi decreased dramatically in the lumbar and sacral segments. Their terminals were present in the ventral horn with a large portion of them terminating in the motor neuron columns. The present study is the first demonstration of the termination pattern of fibers arising from the Gi, DPGi, GiA/GiV, and LPGi in the mouse spinal cord. It provides an anatomical foundation for those who are conducting spinal cord injury and locomotion related research.


Assuntos
Neurônios/citologia , Formação Reticular/citologia , Medula Espinal/citologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais/citologia
9.
Brain Res ; 1542: 85-92, 2014 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-24161824

RESUMO

Prolyl carboxypeptidase (PRCP), a serine protease, is widely expressed in the body including liver, lung, kidney and brain, with a variety of known substrates such as plasma prekallikrein, bradykinin, angiotensins II and III, and α-MSH, suggesting its role in the processing of tissue-specific substrates. In the brain, PRCP has been shown to inactivate hypothalamic α-MSH, thus modulating melanocortin signaling in the control of energy metabolism. While its expression pattern has been reported in the hypothalamus, little is known on the distribution of PRCP throughout the mouse brain. This study was undertaken to determine PRCP expression in the mouse brain. Radioactive in situ hybridization was performed to determine endogenous PRCP mRNA expression. In addition, using a gene-trap mouse model for PRCP deletion, X-gal staining was performed to further determine PRCP distribution. Results from both approaches showed that PRCP gene is broadly expressed in the brain.


Assuntos
Encéfalo/enzimologia , Carboxipeptidases/genética , Carboxipeptidases/metabolismo , RNA Mensageiro/metabolismo , Animais , Galactosídeos/metabolismo , Expressão Gênica , Indóis/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
10.
Neurosci Lett ; 548: 137-42, 2013 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-23756176

RESUMO

Large cholinergic synaptic boutons called "C-terminals" contact motoneurons and regulate their excitability. C-terminals in the spinal somatic motor nuclei originate from cholinergic interneurons in laminae VII and X that express a transcription factor Pitx2. Cranial motor nuclei contain another type of motoneuron: branchiomotor neurons. Although branchiomotor neurons receive abundant C-terminal projections, the neural source of these C-terminals remains unknown. In the present study, we first examined whether cholinergic neurons express Pitx2 in the reticular formation of the adult mouse brainstem, as in the spinal cord. Although Pitx2-positive cholinergic neurons were observed in the magnocellular reticular formation and region around the central canal in the caudal medulla, none was present more rostrally in the brainstem tegmentum. We next explored the origin of C-terminals in the branchiomotor nuclei by using biotinylated dextran amine (BDA). BDA injections into the magnocellular reticular formation of the medulla and pons resulted in the labeling of numerous C-terminals in the branchiomotor nuclei: the ambiguous, facial, and trigeminal motor nuclei. Our results revealed that the origins of C-terminals in the branchiomotor nuclei are cholinergic neurons in the magnocellular reticular formation not only in the caudal medulla, but also at more rostral levels of the brainstem, which lacks Pitx2-positive neurons.


Assuntos
Neurônios Colinérgicos/citologia , Neurônios Colinérgicos/metabolismo , Proteínas de Homeodomínio/metabolismo , Terminações Pré-Sinápticas/metabolismo , Terminações Pré-Sinápticas/ultraestrutura , Formação Reticular/citologia , Formação Reticular/metabolismo , Fatores de Transcrição/metabolismo , Animais , Feminino , Masculino , Camundongos Endogâmicos ICR , Neurônios Motores/citologia , Neurônios Motores/metabolismo , Vias Neurais/citologia , Vias Neurais/metabolismo , Proteína Homeobox PITX2
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