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1.
Acta cir. bras ; 35(7): e202000705, 2020. tab, graf
Article in English | LILACS | ID: biblio-1130657

ABSTRACT

Abstract Purpose Studies have demonstrated that star fruit consumption by nephropathic patients triggers severe neurotoxic effects that can lead to convulsions or even death. Brain areas likely susceptible to star fruit poisoning have not been investigated. The objective of the present study was to map possible epileptogenic areas susceptible to star fruit intoxication in nephropathic rats. Methods The study analyzed 25 rats (5 groups). Rats in the experimental group underwent bilateral ureteral obstruction surgery and orogastric gavages with star fruit juice. An electroencephalogram was used to confirm convulsive seizures. Urea and creatinine levels were used to confirm the uremia model. Immunohistochemical analysis was used to map cells with c-Fos protein (c-Fos+ cells) to identify brain areas with increased neuronal activity. Control groups included non-nephropathic and nephropathic rats that did not receive star fruit. Results A statistically significant increase (p<0.01) in c-Fos+ cells was noted in nephropathic animals receiving star fruit juice compared to control groups, in brain areas commonly related to epileptogenic neural circuits including the hippocampus, amygdala, rhinal cortex, anterior cingulate area, piriform area, and medial dorsal thalamus. Conclusion These data corroborate the neurotoxic capacity of star fruit in nephropathic patients.


Subject(s)
Humans , Animals , Rats , Proto-Oncogene Proteins c-fos , Fruit , Kidney Diseases , Brain , Cerebral Cortex , Proto-Oncogene Proteins c-fos/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Fruit/poisoning , Fruit/poisoning , Hippocampus , Kidney Diseases , Kidney Diseases/complications
2.
An. acad. bras. ciênc ; 89(1): 273-283, Jan,-Mar. 2017. tab, graf
Article in English | LILACS | ID: biblio-886645

ABSTRACT

ABSTRACT Tryptophan is the only precursor of serotonin and mediates serotonergic activity in the brain. Previous studies have shown that the administration of tryptophan or tryptophan depletion significantly alters cognition, mood and anxiety. Nevertheless, the neurobiological alterations that follow these changes have not yet been fully investigated. The aim of this study was to verify the effects of a tryptophan-enriched diet on immunoreactivity to Fos-protein in the rat brain. Sixteen male Wistar rats were distributed into two groups that either received standard chow diet or a tryptophan-enriched diet for a period of thirty days. On the morning of the 31st day, animals were euthanized and subsequently analyzed for Fos-immunoreactivity (Fos-ir) in the dorsal and median raphe nuclei and in regions that receive serotonin innervation from these two brain areas. Treatment with a tryptophan-enriched diet increased Fos-ir in the prefrontal cortex, nucleus accumbens, paraventricular hypothalamus, arcuate and ventromedial hypothalamus, dorsolateral and dorsomedial periaqueductal grey and dorsal and median raphe nucleus. These observations suggest that the physiological and behavioral alterations that follow the administration of tryptophan are associated with the activation of brain regions that regulate cognition and mood/anxiety-related responses.


Subject(s)
Animals , Male , Anxiety/drug therapy , Brain/drug effects , Proto-Oncogene Proteins c-fos/drug effects , Cognition/drug effects , Antidepressive Agents, Second-Generation/administration & dosage , Affect/drug effects , Anxiety/metabolism , Time Factors , Tryptophan/administration & dosage , Brain/metabolism , Immunohistochemistry , Serotonin/metabolism , Reproducibility of Results , Treatment Outcome , Proto-Oncogene Proteins c-fos/metabolism , Rats, Wistar , Dietary Supplements , Diet Therapy/methods
3.
Braz. dent. j ; 27(6): 744-750, Nov.-Dec. 2016. graf
Article in English | LILACS | ID: biblio-828064

ABSTRACT

Abstract The study on the efficacy of oral analgesics reported that no single class of drug is effective in post-surgical dental pain. Pain following removal of third molar is most commonly used and widely accepted acute pain model for assessing the analgesic effect of drugs in humans. Reports demonstrated that analgesic efficacy in the human dental model is highly predictive. The high incidence of false-negative findings in analgesic investigations hinders the process of molecular discovery. Molecular mechanism of post-surgical pain is not known. More importantly, the animal model for postoperative dental pain is not well established. In an attempt to discover an effective post-surgical dental pain blocker with acceptable side effects, it is essential to elucidate the molecular mechanism of post-operative dental pain. The present study investigated mandibular molars extraction in rat as an animal model for the post-operative dental pain in central nervous system. Using c-Fos immunohistochemistry, we demonstrated that pre administration of GBP (150 mg/kg. i.p) significantly (p< 0.01) neutralized the surgical molar extraction induced c-Fos expression bilaterally in rat hypothalamus. Present results indicate that pain after surgical molar extraction might follow novel neural pathways therefore difficult to treat with existing anti-nociceptive drugs.


Resumo O estudo da eficácia relativa dos analgésicos orais relatou que nenhuma classe única de fármaco é eficaz na dor pós-cirúrgica dental. A dor após a remoção do terceiro molar é o modelo de dor aguda mais comumente usado e amplamente aceito para avaliar o efeito analgésico de drogas em seres humanos. Os relatos demonstraram que a eficácia analgésica no modelo dental humano é altamente preditiva. A alta incidência de achados falso-negativos em investigações analgésicas dificulta o processo de descoberta molecular. O mecanismo molecular da dor pós-cirúrgica não é conhecido. Mais importante ainda, o modelo animal para a dor pós-operatória não está bem estabelecido. Numa tentativa de descobrir um bloqueador de dor dental pós-cirúrgico eficaz com efeitos secundários aceitáveis, é essencial elucidar o mecanismo molecular da dor pós-operatória dental. Neste estudo investigamos a extração de molares inferiores de ratos como modelo animal para a dor pós-operatória no sistema nervoso central. Utilizando análise imunohistoquímica de c-Fos, demonstrou-se que a administração prévia de GBP (150 mg/kg i.p) significativamente (p<0,01) neutralizou a expressão c-Fos induzida por extração molar cirúrgica bilateralmente no hipotálamo de rato. Os resultados indicam que a dor após a extração molar cirúrgica pode seguir novas vias neurais, portanto, difícil tratar com as drogas anti-nociceptivas existentes.


Subject(s)
Animals , Male , Rats , Amines/pharmacology , Cyclohexanecarboxylic Acids/pharmacology , gamma-Aminobutyric Acid/pharmacology , Hypothalamus/drug effects , Pain, Postoperative/drug therapy , Proto-Oncogene Proteins c-fos/metabolism , Tooth Extraction/methods , Trigeminal Nucleus, Spinal/drug effects , Amines/therapeutic use , Cyclohexanecarboxylic Acids/therapeutic use , gamma-Aminobutyric Acid/therapeutic use , Hypothalamus/metabolism , Rats, Sprague-Dawley , Tooth Extraction/adverse effects , Trigeminal Nucleus, Spinal/metabolism
4.
Biol. Res ; 49: 1-9, 2016. ilus, graf
Article in English | LILACS | ID: biblio-950859

ABSTRACT

BACKGROUND: Chitosan, the N-deacetylated derivative of chitin, is a cationic polyelectrolyte due to the presence of amino groups, one of the few occurring in nature. The use of chitosan in protein and drug delivery systems is being actively researched and reported in the literature RESULTS: In this study, we used chitosan-coated levodopa liposomes to investigate the behavioral character and the expression of phosphorylated extracellular signal-regulated kinase (ERK1/2), dopamine- and cAMP-regulated phos-phoprotein of 32 kDa (DARPP-32) and FosB/AFosB in striatum of rat model of levodopa-induced dyskinesia (LID). We found that scores of abnormal involuntary movement (AIM) decreased significantly in liposome group (P < 0.05), compared with levodopa group. Levels of phospho-ERK1/2, phospho-Thr34 DARPP-32 and FosB/AFosB in striatum decreased significantly in liposome group lesion side compared with levodopa group (P < 0.05). However, both of two groups above have significantly differences compared with the control group (P < 0.05). CONCLUSION: Chitosan-coated levodopa liposomes may be useful in reducing dyskinesias inducing for Parkinson disease. The mechanism might be involved the pathway of signaling molecular phospho-ERK1/2, phospho-Thr34 DARPP-32 and AFosB in striatum


Subject(s)
Animals , Male , Dopamine Agents/pharmacology , Levodopa/pharmacology , Proto-Oncogene Proteins c-fos/metabolism , Chitosan/pharmacology , Dyskinesia, Drug-Induced/metabolism , Dyskinesia, Drug-Induced/prevention & control , Dopamine and cAMP-Regulated Phosphoprotein 32/metabolism , Parkinson Disease/drug therapy , Phosphorylation/drug effects , Biocompatible Materials/pharmacology , Immunohistochemistry , Random Allocation , Blotting, Western , Reproducibility of Results , Treatment Outcome , Proto-Oncogene Proteins c-fos/analysis , Proto-Oncogene Proteins c-fos/drug effects , Rats, Sprague-Dawley , Corpus Striatum/drug effects , MAP Kinase Signaling System , Extracellular Signal-Regulated MAP Kinases/analysis , Extracellular Signal-Regulated MAP Kinases/drug effects , Dyskinesia, Drug-Induced/etiology , Dopamine and cAMP-Regulated Phosphoprotein 32/analysis , Dopamine and cAMP-Regulated Phosphoprotein 32/drug effects , Nanoparticles , Liposomes
5.
Clinics ; 70(11): 738-742, Nov. 2015. tab
Article in English | LILACS | ID: lil-766147

ABSTRACT

OBJECTIVES: To explore the effects of serum from patients with ankylosing spondylitis on the canonical Wnt/β-catenin pathway and to assess whether the serum has an osteogenic effect in MG63 cells. METHODS: MG63 cells were cultured with serum from 45 ankylosing spondylitis patients, 30 healthy controls, or 45 rheumatoid arthritis patients. The relative PPARD, fra-1, MMP7, OPG and RANKL mRNA levels were measured using quantitative real-time polymerase chain reaction. Associations between gene expression and patient demographics and clinical assessments were then analyzed. RESULTS: MG63 cells treated with serum from ankylosing spondylitis patients had higher PPARD, fra-1, MMP7 and OPG gene expression than did cells treated with serum from controls or rheumatoid arthritis patients (all p<0.05). RANKL expression was higher in MG63 cells treated with serum from patients with ankylosing spondylitis or rheumatoid arthritis than in those treated with serum from controls (both p<0.05). The OPG/RANKL ratio was also higher in MG63 cells treated with serum from ankylosing spondylitis patients than in those treated with serum from controls (p<0.05). No associations were found between the expression of the five genes and the patient demographics and clinical assessments (all p>0.05). CONCLUSIONS : Serum from ankylosing spondylitis patients increases PPARD, fra-1, MMP7, OPG and RANKL expression and the OPG/RANKL ratio in MG63 cells; these effects may be due to the stimulatory effect of the serum on the Wnt pathway.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Arthritis, Rheumatoid/blood , Osteoblasts/metabolism , Serum , Spondylitis, Ankylosing/blood , Cells, Cultured , Culture Media , Cytokines/metabolism , Gene Expression , /metabolism , PPAR delta/metabolism , Proto-Oncogene Proteins c-fos/metabolism , RANK Ligand/metabolism , Real-Time Polymerase Chain Reaction , Wnt Signaling Pathway/genetics , beta Catenin/genetics
7.
Article in English | WPRIM | ID: wpr-24555

ABSTRACT

Natural toxic substances have a bitter taste and their ingestion sends signals to the brain leading to aversive oral sensations. In the present study, we investigated chronological changes in c-Fos immunoreactivity in the nucleus tractus solitarius (NTS) to study the bitter taste reaction time of neurons in the NTS. Equal volumes (0.5 mL) of denatonium benzoate (DB), a bitter tastant, or its vehicle (distilled water) were administered to rats intragastrically. The rats were sacrificed at 0, 0.5, 1, 2, 4, 8, or 16 h after treatment. In the vehicle-treated group, the number of c-Fos-positive nuclei started to increase 0.5 h after treatment and peaked 2 h after gavage. In contrast, the number of c-Fos-positive nuclei in the DB-treated group significantly increased 1 h after gavage. Thereafter, the number of c-Fos immunoreactive nuclei decreased over time. The number of c-Fos immunoreactive nuclei in the NTS was also increased in a dose-dependent manner 1 h after gavage. Subdiaphragmatic vagotomy significantly decreased DB-induced neuronal activation in the NTS. These results suggest that intragastric DB increases neuronal c-Fos expression in the NTS 1 h after gavage and this effect is mediated by vagal afferent fibers.


Subject(s)
Animals , Male , Rats , Adjuvants, Immunologic/pharmacology , Afferent Pathways/physiology , Injections/veterinary , Ligands , Proto-Oncogene Proteins c-fos/metabolism , Quaternary Ammonium Compounds/pharmacology , Rats, Sprague-Dawley , Receptors, G-Protein-Coupled/metabolism , Solitary Nucleus/physiology , Vagus Nerve/drug effects
8.
Gut and Liver ; : 140-147, 2014.
Article in English | WPRIM | ID: wpr-123199

ABSTRACT

BACKGROUND/AIMS: DA-9701, a standardized extract of Pharbitis Semen and Corydalis Tuber, is a new prokinetic agent that exhibits an analgesic effect on the abdomen. We investigated whether DA-9701 affects visceral pain induced by colorectal distension (CRD) in rats. METHODS: A total of 21 rats were divided into three groups: group A (no CRD+no drug), group B (CRD+no drug), and group C (CRD+DA-9701). Expression of pain-related factors, substance P (SP), c-fos, and phosphorylated extracellular signal-regulated kinase (p-ERK) in the dorsal root ganglion (DRG) and spinal cord was determined by immunohistochemical staining and Western blotting. RESULTS: The proportions of neurons in the DRG and spinal cord expressing SP, c-fos, and p-ERK were higher in group B than in group A. In the group C, the proportion of neurons in the DRG and spinal cord expressing p-ERK was lower than that in group B. Western blot results for p-ERK in the spinal cord indicated a higher level of expression in group B than in group A and a lower level of expression in group C than in group B. CONCLUSIONS: DA-9701 may decrease visceral pain via the downregulation of p-ERK in the DRG and spinal cord.


Subject(s)
Animals , Male , Rats , Analgesics/pharmacology , Colon , Dilatation, Pathologic/physiopathology , Down-Regulation , Extracellular Signal-Regulated MAP Kinases/drug effects , Ganglia, Spinal/drug effects , Phytotherapy/methods , Plant Preparations/pharmacology , Proto-Oncogene Proteins c-fos/metabolism , Rats, Sprague-Dawley , Rectum , Spinal Cord/drug effects , Substance P/metabolism , Visceral Pain/prevention & control
9.
Braz. j. med. biol. res ; 46(6): 513-520, 02/jul. 2013. graf
Article in English | LILACS | ID: lil-679201

ABSTRACT

Frogs have been used as an alternative model to study pain mechanisms. Since we did not find any reports on the effects of sciatic nerve transection (SNT) on the ultrastructure and pattern of metabolic substances in frog dorsal root ganglion (DRG) cells, in the present study, 18 adult male frogs (Rana catesbeiana) were divided into three experimental groups: naive (frogs not subjected to surgical manipulation), sham (frogs in which all surgical procedures to expose the sciatic nerve were used except transection of the nerve), and SNT (frogs in which the sciatic nerve was exposed and transected). After 3 days, the bilateral DRG of the sciatic nerve was collected and used for transmission electron microscopy. Immunohistochemistry was used to detect reactivity for glucose transporter (Glut) types 1 and 3, tyrosine hydroxylase, serotonin and c-Fos, as well as nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase). SNT induced more mitochondria with vacuolation in neurons, satellite glial cells (SGCs) with more cytoplasmic extensions emerging from cell bodies, as well as more ribosomes, rough endoplasmic reticulum, intermediate filaments and mitochondria. c-Fos immunoreactivity was found in neuronal nuclei. More neurons and SGCs surrounded by tyrosine hydroxylase-like immunoreactivity were found. No change occurred in serotonin- and Glut1- and Glut3-like immunoreactivity. NADPH-diaphorase occurred in more neurons and SGCs. No sign of SGC proliferation was observed. Since the changes of frog DRG in response to nerve injury are similar to those of mammals, frogs should be a valid experimental model for the study of the effects of SNT, a condition that still has many unanswered questions.


Subject(s)
Animals , Male , Ganglia, Spinal/metabolism , Ganglia, Spinal/ultrastructure , Oxidoreductases/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Sciatic Nerve/injuries , Serotonin/metabolism , Cellular Microenvironment , Glucose Transport Proteins, Facilitative/metabolism , Immunohistochemistry , Microscopy, Electron, Transmission , NADPH Dehydrogenase/metabolism , Neuralgia/metabolism , Rana catesbeiana , /metabolism
10.
Article in English | WPRIM | ID: wpr-57561

ABSTRACT

Although mounting evidence indicates the involvement of galectin-3 in cancer progression and metastasis, the underlying molecular mechanisms remain largely unknown. In this study, we investigated the effect and possible mechanism of galectin-3 on the migration and invasion of B16F10, a metastatic melanoma cell line, in which galectin-3 and matrix metalloproteinase-1 (MMP-1) were both found to be highly expressed. Knockdown of galectin-3 with specific siRNA reduced migration and invasion, which was associated with reduced expression of MMP-1. To further investigate the underlying mechanism, we examined the effect of galectin-3 knockdown on the activity of AP-1, a transcriptional factor regulating MMP-1 expression. We found that galectin-3 directly interacted with AP-1 and facilitated the binding of this complex to the MMP-1 promoter that drives MMP-1 transcription. Moreover, silencing of galectin-3 inhibited binding of fra-1 and c-Jun to promoter sites of MMP-1 gene. Consistent with these in vitro findings, our in vivo study demonstrated that galectin-3 shRNA treatment significantly reduced the total number of mouse lung metastatic nodules. Taken together, galectin-3 facilitates cell migration and invasion in melanoma in vitro and can induce metastasis in vivo, in part through, regulating the transcription activity of AP-1 and thereby up-regulating MMP-1 expression.


Subject(s)
Animals , Mice , Binding Sites/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Galectin 3/genetics , JNK Mitogen-Activated Protein Kinases/metabolism , Lung Neoplasms/drug therapy , Matrix Metalloproteinase 1/genetics , Melanoma, Experimental/metabolism , Mice, Inbred C57BL , NIH 3T3 Cells , Neoplasm Metastasis , Promoter Regions, Genetic , Proto-Oncogene Proteins c-fos/metabolism , RNA Interference , RNA, Small Interfering , Transcription Factor AP-1/genetics , Transcription, Genetic , Transcriptional Activation
11.
Article in English | WPRIM | ID: wpr-221048

ABSTRACT

PURPOSE: To investigate the effect of dark rearing immediately after birth on the maturation of the visual relay neurons in the lateral geniculate nucleus. METHODS: Fifty neonatal rats were used. Neonates of the control groups were raised under a normal light/dark cycle. Neonates of the experiment groups were dark reared and isolated from light during the entire experimental period, then exposed to the sun light for 1 hour before sacrifice. RESULTS: In the control groups, the neurons in the dorsal lateral geniculate nucleus developed normally at each age tested. In the experiment groups, the cytoplasm of the large neurons in the dorsal lateral geniculate nucleus of 2-week-old rats contained small vesicles, and the cytoplasm of the large neurons of 4-week-old rats was converted into a vacuole-like space. Moreover, c-Fos immunoreactivity of the large neurons in the dorsal lateral geniculate nucleus in the experiment groups was significantly increased compared to that of the control groups. CONCLUSIONS: We suppose that the maturation of the neurons in the lateral geniculate nucleus might be influenced by light stimulation during the critical period. Furthermore, c-Fos could be a marker of the functional activity of the visual relay neurons of the lateral geniculate nucleus in albino rats.


Subject(s)
Animals , Rats , Animals, Newborn , Critical Period, Psychological , Dark Adaptation , Geniculate Bodies/metabolism , Immunohistochemistry , Light , Neurons/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Rats, Sprague-Dawley
12.
Journal of Forensic Medicine ; (6): 321-324, 2010.
Article in Chinese | WPRIM | ID: wpr-983586

ABSTRACT

OBJECTIVE@#To explore the changes of c-fos in apoptosis of cerebellar granular neuron of neonatal SD rats induced by heroin and the mechanisms of neuronal injury caused by heroin.@*METHODS@#Primary cerebellar granular neuron were cultured in vitro, the model of apoptosis induced by heroin was established. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were adopted to investigate the changes of c-fos in cell models.@*RESULTS@#Ten microg/mL of heroin was the optimal dose to induce the apoptosis of cerebellar granular neuron at 48 h. Both Western blotting and RT-PCR showed down regulation of c-fos expression.@*CONCLUSION@#Heroin could induce apoptosis of cerebellar granular neuron and down regulation of c-fos, which may be one of the apoptosis mechanisms.


Subject(s)
Animals , Male , Rats , Animals, Newborn , Apoptosis/drug effects , Blotting, Western , Cells, Cultured , Cerebellum/metabolism , Dose-Response Relationship, Drug , Down-Regulation , Gene Expression Regulation/drug effects , Heroin/pharmacology , Neurons/metabolism , Proto-Oncogene Proteins c-fos/metabolism , RNA, Messenger/metabolism , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction
13.
Article in English | WPRIM | ID: wpr-44276

ABSTRACT

Corticotrophin-releasing factor (CRF), a key regulator of the hypothalamic-pituitary axis, is expressed in the central nucleus of the amygdala (CeA) and its expression is upregulated in stress-related disorders. We investigated here the effect of noxious colorectal distension (CRD) on the expression of CRF in the CeA of conscious and unconscious rats. Adult male rats with or without general anesthesia were exposed to visceral pain induced by CRD for 5 min; this procedure was repeated 3 times with 1 min resting after each distension. The rats were sacrificed and sections of the CeA were immunostained for CRF as an indicator for anxiety response, and for phosphorylated extracellular signal-regulated kinase (p-ERK) as a marker for pain-specific activation of neurons; sections of lumbosacral spinal cord were immunostained for c-Fos as a marker for activation of spinal neurons. CRD elicited a significant increase in the expression of CRF and p-ERK in the CeA and of c-Fos in the spinal cord. General anesthesia attenuated the increase in CRF and p-ERK in the CeA, but did not affect the expression of spinal c-Fos. These results suggest that conscious recognition of pain at higher brain centers is an important determinant of CRF expression in the CeA.


Subject(s)
Animals , Male , Rats , Amygdala/metabolism , Anesthesia, General , Colon , Corticotropin-Releasing Hormone/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Immunohistochemistry , Neurons/metabolism , Pain/prevention & control , Phosphorylation , Proto-Oncogene Proteins c-fos/metabolism , Rats, Sprague-Dawley , Rectum
14.
Saudi Medical Journal. 2010; 31 (9): 974-979
in English | IMEMR | ID: emr-117664

ABSTRACT

To investigate the effects of a Chinese herb Cordyceps sinensis [C. sinensis] extract on hypoxia-induced proliferation and the underlying mechanisms involved. This prospective study was carried out at the Central Laboratory of Yichang Central People's Hospital, Yichang, China from March 2008 to April 2010. The C. sinensis was extracted from the Chinese herb C. sinensis using aqueous alcohol extraction techniques. Forty healthy adult male Sprague Dawley rats were used in the study. The proliferation of pulmonary artery smooth muscle cells [PASMCs] was measured using 3-[4,5-dimethylthiazol-2-Yl]-2,5-diphenyltetrazolium bromide [MTT] assay, and cell viability was determined by trypan blue exclusion. Cell cycles were analyzed using FACSort flow cytometric analysis. The expression of proliferating cell nuclear antigen [PCNA], c-jun, and c-fos in rat PASMCs was determined by immunohistochemistry. We found an increased proliferation of PASMCs and increased expression of transcription factors, c-jun and c-fos in PASMCs cultured under hypoxic conditions. The C. sinensis extract significantly inhibited hypoxia-induced cell proliferation in a dose-dependent manner. In addition, C. sinensis extract also significantly inhibited the expression of PCNA, c-jun, and c-fos in these PASMCs. Our results indicated that C sinensis extract inhibits hypoxia-induced proliferation of rat PASMCs, probably by suppressing the expression of PCNA, c-fos, c-jun, and decreasing the percentage of cells in synthesis phase, second gap phase, and mitotic phase in cell cycle [S+G[2]/M] phase. Our results therefore, provided novel evidence that C. sinensis extract may be used as a therapeutic reagent in the treatment of hypoxic pulmonary hypertension


Subject(s)
Animals , Male , Hypoxia/drug therapy , Muscle, Smooth, Vascular/drug effects , Pulmonary Artery , Hypoxia/physiopathology , Cell Proliferation/drug effects , Proto-Oncogene Proteins c-fos/metabolism , Proto-Oncogene Proteins c-jun/metabolism , Rats, Sprague-Dawley
15.
Article in English | WPRIM | ID: wpr-10970

ABSTRACT

BACKGROUND/AIMS: The present study was performed to determine the effects of the ethyl acetate extract of Cudrania tricuspidata (EACT) on interleukin (IL)-1beta-stimulated receptor activator of NF-kappaB ligand (RANKL)-mediated osteoclast differentiation. METHODS: Bone marrow cells were harvested from 6-week-old male imprinting control region mice, and the differentiation of osteoclasts from these cells was evaluated by tartrate-resistant acid phosphatase and resorption pit formation assay. Phosphorylated extracellular signal regulated kinase (p-ERK), phosphorylated p38, phosphorylated c-Jun amino-terminal kinase, NF-kappaB (p65), IkappaBalpha, c-Fos, and nuclear factor of activated T-cells c1 (NFATc1) expression was examined by immunoblotting and quantitative reverse transcription-polymerase chain reaction. RESULTS: EACT inhibits IL-1beta-stimulated RANKL-mediated osteoclast differentiation. EACT also inhibits IL-1beta-stimulated RANKL-mediated phosphorylation of ERK 1/2, p38 mitogen activated protein kinase, and expression of c-Fos and NFATc1. CONCLUSIONS: These results suggest that EACT may be involved in the inhibition of bone loss by preventing osteoclast formation and may be used to manage bone destruction in inflammatory diseases, such as rheumatoid arthritis.


Subject(s)
Animals , Male , Mice , Acetates , Bone Marrow Cells/cytology , Cell Differentiation/drug effects , Cell Survival/drug effects , Cells, Cultured , Down-Regulation/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Interleukin-1beta/pharmacology , MAP Kinase Signaling System/drug effects , Mice, Inbred ICR , Moraceae , NFATC Transcription Factors/metabolism , Osteoclasts/cytology , Plant Extracts/pharmacology , Proto-Oncogene Proteins c-fos/metabolism , RANK Ligand/metabolism , Stem Cells/cytology , p38 Mitogen-Activated Protein Kinases/metabolism
16.
Article in Chinese | WPRIM | ID: wpr-983431

ABSTRACT

OBJECTIVE@#To explore the effects of curcumin on the content of malondialdehyde (MDA) and the expression level of c-fos protein following hypoxia ischemia brain damage (HIBD) in rats.@*METHODS@#Sprague-Dauley (SD) rats were randomly divided into four groups as the following: sham group, hypoxia ischemia brain damage group, curcumin group and solvent control group. The content of MDA in the brain was measured by colorimetry. The expression level of c-fos protein in the cortex tissue was detected by immunohistochemistry. Morphologic and structural changes of neuron cells of the cortex were observed by electron microscopy.@*RESULTS@#The content of MDA was clearly lower in curcumin group than that in the other groups at the same time after HIBD. The expression level of c-fos protein was higher in the curcumin group than that in the other groups (P<0.05). Electron microscopy showed that the morphologic and structural changes of neuron cells of cortex in the curcumin group were reduced.@*CONCLUSION@#Curcumin could significantly decrease the content of MDA, increase the expression level of c-fos protein and reduce the damage of the neuron cells.


Subject(s)
Animals , Male , Rats , Curcumin/pharmacology , Forensic Pathology , Hypoxia-Ischemia, Brain/pathology , Malondialdehyde/metabolism , Neurons/pathology , Neuroprotective Agents/pharmacology , Proto-Oncogene Proteins c-fos/metabolism , Random Allocation , Rats, Sprague-Dawley
17.
Braz. j. med. biol. res ; 41(10): 920-925, Oct. 2008. ilus, graf
Article in English | LILACS | ID: lil-496807

ABSTRACT

Dopaminergic neurotransmission is involved in the regulation of sleep. In particular, the nigrostriatal pathway is an important center of sleep regulation. We hypothesized that dopaminergic neurons located in substantia nigra pars compacta (SNpc) could be activated by gentle handling, a method to obtain sleep deprivation (SD). Adult male C57/BL6J mice (N = 5/group) were distributed into non-SD (NSD) or SD groups. SD animals were subjected to SD once for 1 or 3 h by gentle handling. Two experiments were performed. The first determined the activation of SNpc neurons after SD, and the second examined the same parameters after pharmacologically induced dopaminergic depletion using intraperitoneal reserpine (2 mg/kg). After 1 or 3 h, SD and NSD mice were subjected to motor evaluation using the open field test. Immediately after the behavioral test, the mice were perfused intracardially to fix the brain and for immunohistochemical analysis of c-Fos protein expression within the SNpc. The open field test indicated that SD for 1 or 3 h did not modify motor behavior. However, c-Fos protein expression was increased after 1 h of SD compared with the NSD and 3-h SD groups. These immunohistochemistry data indicate that these periods of SD are not able to produce dopaminergic supersensitivity. Nevertheless, the increased expression of c-Fos within the SNpc suggests that dopaminergic nigral activation was triggered by SD earlier than motor responsiveness. Dopamine-depleted mice (experiment 2) exhibited a similar increase of c-Fos expression compared to control animals indicating that dopamine neurons are still activated in the 1-h SD group despite the exhaustion of dopamine. This finding suggests that this range (2-5-fold) of neuronal activation may serve as a marker of SD.


Subject(s)
Animals , Male , Mice , Dopamine/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Sleep Deprivation/metabolism , Substantia Nigra/metabolism , Immunohistochemistry , Motor Activity/physiology , Reserpine/pharmacology , Time Factors
18.
Yonsei Medical Journal ; : 479-485, 2008.
Article in English | WPRIM | ID: wpr-79503

ABSTRACT

PURPOSE: c-fos expression in spinal neurons that are activated by lower urinary tract stimulation are not organ specific. In this experiment, we demonstrated changes of c-fos expression in bladder-specific preganglionic neurons (PGNs) and interneurons using pseudorabies virus (PRV). MATERIALS AND METHODS: Forty Sprague-Dawley rats were used. We identified the neuronal pathway associated with the bladder by injecting PRV into the detrusor. An immunohistochemical method was used to stain Fos-protein encoded by the c-fos gene. Immunofluorescent staining for PRV was performed to evaluate changes in bladder-specific spinal neurons. RESULTS: Immunofluorescent staining with choline acetyltransferase (ChAT) revealed that the sacral parasympathetic nucleus (SPN) regions contained 9.8 PGNs/ section. In rats with chronic spinal cord injury by intravesical saline instillation, 82.4+/-10.3% of PGNs in SPN exhibited Fos-immunoreactive (IR). Two and a half days after PRV infection, PRV-IR PGNs were observed at 5.4 PGNs/ section, and 2.7+/-1.6% of them exhibited Fos-IR. Unlike ChAT-IR PGNs, PRV-IR PGNs are bladder-specific neurons and PRV-IR and Fos-IR cells found in the back of PRV-IR PGNs are bladder- specific interneurons. Three days after PRV infection, we observed many PRV-IR and Fos-IR cells in the dorsal commissure. These neurons are interneurons distributed in the bladder. CONCLUSION: We confirmed that in chronic spinal cord injury, the patterns of c-fos expression in bladder-specific spinal neurons were similar to those in voiding-reflex related spinal neurons, which had already been demonstrated earlier. We believe that our methodology can be applied to study interactions between voiding and other organs as well, such as the urethra and prostate.


Subject(s)
Animals , Female , Rats , Herpesvirus 1, Suid/physiology , Immunohistochemistry , Interneurons/cytology , Neurons/cytology , Proto-Oncogene Proteins c-fos/metabolism , Rats, Sprague-Dawley , Spinal Cord Injuries/physiopathology , Urinary Bladder/cytology
19.
Article in Chinese | WPRIM | ID: wpr-983342

ABSTRACT

OBJECTIVE@#To study the mRNA expression of BNP and c-fos gene in rat heart after acute myocardial ischemia (AMI) and to provide a marker for its medicolegal diagnosis.@*METHODS@#AMI animal model of rat was made by ligating LAD. mRNA expression of BNP and c-fos gene were studied with RT-qPCR and ordinary PCR at 10 min, 30 min, 60 min and 3h after the successful ligation. The H&E staining was also used. Changes of the mRNA expression in different time groups were compared.@*RESULTS@#There was significant difference in BNP mRNA expression of the 3 h group by RT-qPCR compared with normal control group, 10 min, 30 min, and 60 min groups (P < 0.05). There were dramatic differences in c-fos mRNA expression between every two groups (P < 0.05) except between the normal group and the 10 min group, between the 30 min group and the 3 h group. The peak of c-fos expression was in 60 min group. No difference was shown between groups by the ordinary PCR. Myocardial fiber acidophilia staining and wavy changes could be seen occasionally at 3 h experimental group by H&E staining.@*CONCLUSIONS@#C-fos gene probably be used as an auxiliary test for myocardial ischemia of duration of 30 minutes or longer. RT-qPCR may be suitable for diagnosis of early AMI.


Subject(s)
Animals , Male , Rats , Biomarkers/metabolism , Forensic Medicine , Myocardial Ischemia/metabolism , Natriuretic Peptide, Brain/metabolism , Proto-Oncogene Proteins c-fos/metabolism , RNA, Messenger/metabolism , Random Allocation , Rats, Sprague-Dawley , Time Factors
20.
Journal of Forensic Medicine ; (6): 245-251, 2008.
Article in Chinese | WPRIM | ID: wpr-983386

ABSTRACT

OBJECTIVE@#To study the changes of HSP 70 mRNA and c-fos mRNA expression and to find a method to differentiate antemortem from postmortem electrocution.@*METHODS@#Fifteen New Zealand rabbits were randomly divided into three groups, the antemortem electrocution group, the postmortem electrocution group, and the control group. Each group consists of five rabbits. The levels of HSP 70 mRNA and c-fos mRNA in skeletal muscle and cardiac muscle were examined with quantitative fluorescent RT-PCR.@*RESULTS@#The levels of HSP 70 mRNA and c-fos mRNA in the antemortem electrocution group increased significantly (P<0.05), compared with that of the postmortem electrocution group.@*CONCLUSION@#The changes of HSP 70 mRNA and c-fos mRNA expression in skeletal muscle and cardiac muscle can be used as an indicator to distinguish antemortem from postmortem electrocution.


Subject(s)
Animals , Male , Rabbits , Electric Injuries/metabolism , Forensic Pathology , HSP70 Heat-Shock Proteins/metabolism , Muscle, Skeletal/metabolism , Myocardium/metabolism , Postmortem Changes , Proto-Oncogene Proteins c-fos/metabolism , RNA, Messenger/metabolism , Random Allocation
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