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E Senba

Publications and source records attributed to E Senba.

At least 73 records · Page 4Linked to original sources
PubMed1997

Intradermal 5-HT induces Fos expression in rat dorsal horn neurons not via 5-HT3 but via 5-HT2A receptors.

We investigated the effects of peripherally administered 5-HT on the secondary neurons in the spinal cord of rats using Fos-like immunoreactivity (FLI) as a marker of neuronal activation. The intradermal administration of 5-HT (30, 60 microg) induced a large number of FLI neurons in the ipsilateral dorsal horn. In animals given 5-HT2A receptor agonists (DOI: 0.28 to 2.8 micromol/kg, alpha-methyl 5-HT: 0.28 to 2.8 micromol/kg) intradermally, immunoreactive neurons were evoked in the same manner as those given 5-HT. Other agonists, including 5-HT3 receptor agonists (m-CPG: 16 to 32 micromol/kg, 2-methyl 5-HT: 0.0028 to 2.8 micromol/kg), did not induce FLI neurons at any dose examined. Furthermore, 5-HT2A receptor antagonist (ketanserin: 1 mg/kg, i.p.) suppressed the expression of FLI in the dorsal horn caused by peripheral 5-HT, but 5-HT3 receptor antagonist (tropisetron: 1 mg/kg, i.p.) did not. These findings suggest that the 5-HT-induced nociceptive response is mediated by 5-HT2A receptors in the periphery.

Animals↗
PubMed1997

Stress-induced expression of immediate early genes in the brain and peripheral organs of the rat.

Stress causes rapid and transient expression of immediate early genes (IEGs) in the brain, and the monitoring of IEGs has enabled the visualization of the neurocircuitry of stress. Previous studies have postulated that stressors can be divided into two categories; processive and systemic. The neural circuits of brain activation differ between the two kinds of stressors. For example, processive stressors, such as immobilization (IMO), induce c-fos mRNA first in the cortical and limbic areas and then in the paraventricular hypothalamic nucleus (PVH), while c-fos expression in the PVH precedes that in other areas in animals subjected to systemic stressors. We further show that prior exposure to IMO stress for 6 days, or implantation of corticosterone pellets suppresses the induction of c-fos, fos B, jun B and NGFI-B, but not that of NGFI-A in the rat PVH. Plasma glucocorticoid may be an important factor regulating stress-induced IEG expression. It is well known that AP-1 and glucocorticoid receptors (GR) interact and suppress each other. Thus, decreased AP-1 levels in chronically stressed animals may help enhance the negative feedback effects of GR and prevent hypersecretion of glucocorticoid, which is implicated in the pathogenesis of stress-related diseases. IMO stress induces rapid expression of c-fos, c-jun and NGFI-A mRNAs in the heart and stomach. These were observed in the ventricular myocardium and coronary arteries, and in the epithelium, smooth muscles and arteries of the stomach after 30 min of IMO. IEG expression in the peripheral organs may provide a molecular basis for stress-induced psychosomatic disorders.

Animals↗
PubMed1997

Systemic capsaicin in the adult rat differentially affects gene expression for neuropeptides and neurotrophin receptors in primary sensory neurons.

While systemic capsaicin in adult rats is known to reduce substance P and somatostatin in primary sensory nerves, it is still unknown if it also affects the production of these peptides at the genetic level. Therefore, we examined the effects of systemically administered capsaicin on the expression of the beta-preprotachykinin, gamma-preprotachykinin, somatostatin, calcitonin gene-related peptide, vasoactive intestinal polypeptide, galanin, neuropeptide Y and neurotrophin receptor family (trkA, trkB, trkC) genes in dorsal root ganglion neurons by in situ hybridization in adult rats. Nerve growth factor is thought to be involved in the regulation of some of these genes. In the control animals, beta-preprotachykinin, gamma-preprotachykinin, calcitonin gene-related peptide, somatostatin, trkA, trkB and trkC messenger RNAs were found in about 30%, 30%, 40%, 10%, 40%, 5% and 20% of the lumbar dorsal root ganglion neurons, respectively. The number of neurons expressing beta/gamma-preprotachykinin and calcitonin gene-related peptide messenger RNAs decreased to about 50% and 70% of the control values, respectively, six days after subcutaneous administration of capsaicin (950 mg/kg). Simultaneously, the number of trkA messenger RNA-expressing neurons also decreased to about 70% of the control level, while the number of neurons expressing trkB and trkC messenger RNAs was unaffected. On the other hand, vasoactive intestinal polypeptide and galanin messenger RNAs, but not neuropeptide Y messenger RNA, began to be expressed in about 10% of dorsal root ganglion neurons after administration of capsaicin, although their messenger RNAs were not detected in the controls. However, the expression of somatostatin messenger RNA was unaffected by the systemic administration of capsaicin. The somatostatin messenger RNA was not co-expressed with vasoactive intestinal polypeptide and galanin messenger RNAs in the sensory neurons of rats given capsaicin. Electron microscopic analysis revealed a few degenerating unmyelinated afferents in sural nerves of the treated rats. The number of small-sized dorsal root ganglion cells labeled with Fluoro-Gold, a retrograde-tracing dye which was injected into the sural nerve of the treated rats, decreased to half of the control number. Our results suggest that systemic administration of capsaicin in adult rats depresses the expression of beta/gamma-preprotachykinin, calcitonin gene-related peptide and trkA messenger RNAs, and induces expression of vasoactive intestinal polypeptide and galanin messenger RNAs in sensory neurons, which may be due to the capsaicin-induced degeneration of a subpopulation of sensory afferents. We also demonstrated that the regulation of somatostatin gene expression in mature sensory neurons is not affected by systemic capsaicin.

Animals↗
PubMed1997

Chronic glucocorticoid administration as well as repeated stress affects the subsequent acute immobilization stress-induced expression of immediate early genes but not that of NGFI-A.

We reported that repeated immobilization for six days attenuates the subsequent acute immobilization stress-induced expression of the immediate early genes c-fos, fos B, jun B and nerve growth factor-induced gene-B (NGFI-B), but not of NGFI-A, in the rat paraventricular hypothalamic nucleus. In this study, we confirmed these findings by means of a time-course study, and further investigated whether the elevated plasma basal glucocorticoid level induced by repeated stress underlies the attenuated response of immediate early genes and the preserved reactivity of NGFI-A. Rats implanted with 100, 200 or 400 mg corticosterone or placebo pellets (control), were immobilized for 1 h and decapitated seven days later. In control rats acute immobilization induced c-fos, fos B, jun B, NGFI-A and NGFI-B messenger RNA in the paraventricular hypothalamic nucleus, whereas all of them except NGFI-A, were significantly reduced in rats given 200 and 400 mg corticosterone implants. The similarity of the results from the two procedures suggests that glucocorticoid is involved in regulating immediate early genes in the paraventricular hypothalamic nucleus under repeated stress and that the NGFI-A gene is not regulated by this mechanism. However, the plasma basal corticosterone level in repeatedly stressed rats was lower than that of rats implanted with 100 mg corticosterone, suggesting that a repetitive stress-induced corticosterone surge also contributes to this mechanism.

Animals↗
PubMed1997

[Expression of neurotrophin and IL-1 beta mRNAs following spinal cord injury and the effects of methylprednisolone treatment].

Glucocorticoid has been clinically used for the treatment of acute spinal cord injury (SCI) to enhance the neurological recovery, but the relevance of the use of steroid is not fully discussed. Neurotrophins play important roles in normal development of central and peripheral nervous system. It is reported that traumatic insults to the brain alter the expression of these neurotrophins. These responses are considered to trigger a cascade of cellular protection and repair. First, we investigated the temporal and spatial expression patterns of neurotrophin and IL-1 beta mRNAs in the area of spinal cord lesion. Second, we examined if methylprednisolone (MP) affects the expression of these genes in SCI. Male Sprague-Dawley rats (250-300 gms) were laminectomized at T10. Spinal cord was crushed by clipping (holding force 60 gms, 1 sec). Rats were killed at 1, 6, 12, 24 h, and 72 h after the injury and the spinal cord was rapidly removed and frozen sections were cut. Second, the other group of rats were treated with MP (165 mg/kg) just after SCI and sacrificed at 6 h. The levels of neurotrophins and IL-1 beta mRNAs were evaluated by in situ hybridization histochemistry. IL-1 beta mRNA level was elevated at 1 h and 6 h and attenuated at 12 h. The increased level of BDNF and NT3 mRNAs were first observed at 6 h and the labeling was enhanced at 24 h and 72 h. In MP treated group, the levels of IL-1 beta, BDNF and NT3 mRNAs were attenuated compared with those of MP-untreated SCI group. Steroid hormone therapy diminishes the post-traumatic inflammatory cascades which produce edema and swelling and worsen neuronal injury. However, glucocorticoid may hinder the endogenous repair mechanism. Our data show that MP depress the production of BDNF and NT3 following SCI, which might be disadvantageous to the survival of spinal neurons.

Animals↗
PubMed1996

Mutation of the trkB gene encoding the high-affinity receptor for brain-derived neurotrophic factor in stroke-prone spontaneously hypertensive rats.

Brain-derived neurotrophic factor and its receptor, trkB, are thought to play a crucial role for protection against neuronal death induced by brain ischemia, such as in stroke. In the present study we found a missense mutation in the trkB gene from all of the five substrains of stroke-prone spontaneously hypertensive rats (SHRSP) that were examined. This mutation was not found in six out of seven hypertensive but stroke-resistant ancestral strains (SHR) of SHRSP, nor in any of seven strains of normotensive, non-stroke-prone strains. Hippocampal neurons, which are particularly vulnerable to damage in stroke, were shown to be more susceptible to ischemic damage in SHRSP than in either SHR or normotensive, stroke-resistant controls. The association of a mutated trkB gene with the stroke-prone genotype found in this study suggests that the trkB gene merits further study as a promising candidate gene for stroke.

Animals↗
PubMed1996

Organization of excitatory and inhibitory local networks in the caudal nucleus of tractus solitarius of rats revealed in in vitro slice preparation.

Morphological and physiological properties of neurons in the caudal nucleus of tractus solitarius (NTS) of rats were studied in vitro by whole-cell recording and intracellular staining with biocytin. Synaptic responses following the solitary tract stimulation were also investigated to elucidate anatomical substrates of the underlying local circuits. Biocytin-filled NTS cells were divided into three groups according to the pattern of their axonal arborization: (1) local circuit neurons whose axon collaterals were extensively distributed within the NTS with the main axons leaving the NTS; (2) presumed interneurons whose axon collaterals seemed to be restricted within the NTS; and (3) projection neurons whose axons had few, if any, collaterals. Both local circuit neurons and presumed interneurons had small cell bodies (< 150 microns2 in somal area) and exhibited tonic regular spiking at depolarized membrane potentials. Polysynaptic excitatory background activity was increased and lasted for 300-1000 msec in these neurons following solitary tract stimulation. The projection neurons had medium to large cell bodies (> 150 microns2 in somal area). Inhibitory postsynaptic responses produced by an increased CI-conductance were recorded in these projection neurons. These findings suggest that excitatory local networks are organized by an assembly of the local circuit neurons in the caudal NTS, and that the interneurons are arranged to connect the excitatory local network with medium to large projection neurons via inhibitory synapses. Visceral afferent information is probably processed in the highly organized excitatory and inhibitory local networks within the caudal NTS and conveyed to other brain regions.

Afferent Pathways↗
PubMed1996

Mutation of low affinity nerve growth factor receptor gene is associated with the hypertensive phenotype in spontaneously hypertensive inbred rat strains.

We previously reported a missense mutation in the low affinity nerve growth factor receptor (LNGFR) gene of spontaneously hypertensive rats (SHR), proposing this gene as a promising candidate in genetic hypertension. In this study we provide further support for implicating this gene in genetic hypertension using two new inbred strains, WKHT and WKHA rats. These strains originated from crossbreeding SHR rats with normotensive Wistar-Kyoto rats (WKY): WKHT rats are hypertensive but not hyperactive, and WKHA rats are hyperactive but not hypertensive. Nucleotide sequence analysis of the LNGFR gene revealed that WKHT has the same mutation as SHR, whereas WKHA has the normal sequence, as seen in WKY. These results support our original hypothesis that the mutated LNGFR gene is linked to hypertension, since the mutation had co-segregated with the hypertensive trait, and not hyperactivity trait of SHR.

Amino Acid Sequence↗
PubMed1996

Immobilization stress induces c-fos and c-jun immediate early genes expression in the heart.

Emotional stress is considered to be one of the etiological factors in ischemic heart disease (IHD) and sudden cardiac death (SCD), mechanisms of which are poorly understood. Immediate early genes (IEGs), such as c-fos and c-jun are used as tools for detection of cellular activation. Male Wistar rats were exposed to acute immobilization (IMO). IMO stress for 30 min induced c-fos and c-jun mRNAs expression in the myocardium and the smooth muscle layer of the coronary arteries. IMO stress for 2 h also induced Fos and Jun like-immunoreactivities in the same regions. Distribution of IEG mRNAs and their protein products in the myocardium was not uniform but rather localized. These data provided histological evidence for an early cellular event in the stress response whose consequences could result in activation of tissues in the myocardium and coronary arterial smooth muscle cells which play a role in the pathophysiological changes in IHD and SCD.

Animals↗
PubMed1996

Coexpression of preprotachykinin-A, alpha-calcitonin gene-related peptide, somatostatin, and neurotrophin receptor family messenger RNAs in rat dorsal root ganglion neurons.

Syntheses of substance P, somatostatin, and calcitonin gene-related peptide in sensory neurons have been suggested to be regulated by neurotrophic factors retrogradely transported from target tissues. In this study, we re-examined this idea by investigating the coexpression of neurotrophin receptor (trk family proto-oncogene) messenger RNAs, and preprotachykinin-A (a precursor peptide of substance P), alpha-calcitonin gene-related peptide and somatostatin messenger RNAs in lumbar dorsal root ganglion neurons by means of in situ hybridization histochemistry in rats. Approximately 35-40%, 5% and 15-20% of sensory neurons displayed signals for trkA, trkB, and trkC messenger RNAs, respectively. Approximately 28% of dorsal root ganglion neurons were positive for preprotachykinin-A messenger RNA, and were divided into two groups; those labeled strongly and those labeled weakly by in situ hybridization. All the strongly-labeled neurons (78% of preprotachykinin-A-positive cells) expressed trkA messenger RNA at the same time, while the weakly-labeled neurons did not. Thirty-seven per cent of dorsal root ganglion neurons expressed alpha-calcitonin gene-related peptide messenger RNA, and most of these neurons (84%) also expressed trkA messenger RNA. No or few preprotachykinin-A messenger RNA- and/or alpha-calcitonin gene-related peptide messenger RNA-expressing neurons were also positive for trkB or trkC messenger RNAs. Nine per cent of dorsal root ganglion neurons expressed somatostatin messenger RNA, and these neurons lacked all three trk messenger RNAs. Furthermore, most of these neurons (about 90%) showed positive, albeit weak, signals for preprotachykinin-A and alpha-calcitonin gene-related peptide messenger RNAs. The results suggest that expression of preprotachykinin-A and alpha-calcitonin gene-related peptide messenger RNAs is mediated by nerve growth factor via trkA receptor but not by brain-derived neurotrophic factor or neurotrophin-3, and that somatostatin gene transcription is not regulated by any member of the neurotrophin family in rat sensory neurons.

Animals↗
PubMed1996

Sensory afferent processing in multi-responsive DRG neurons.

The recent advance in molecular and neurobiological techniques disclosed the multi-responsive nature of DRG neurons. The survival, phenotype expression and electrical properties of these neurons are under the control of a variety of substances through their specific receptors. In pathological conditions, such as tissue inflammation or nerve injury, DRG neurons change their responsiveness through the dynamic reconstruction of their receptor system. This reconstruction is initiated by environmental stimuli. Thus the properties of polymodal nociceptors can be altered according to the environmental conditions. The whole story of this mechanism is not disclosed yet. In order to understand this mechanism, it is basically important to identify various receptor mRNAs in DRG neurons, precise localization of receptor proteins, site of synthesis and route of supply of ligands for these receptors.

Animals↗
PubMed1996

Nitric oxide synthase-containing magnocellular neurons of the rat hypothalamus synthesize oxytocin and vasopressin and express Fos following stress stimuli.

We investigated the chemical and anatomical features of nitric oxide synthase (NOS)-containing neurons in the paraventricular and supraoptic nuclei in the rat hypothalamus using combinations of enzyme histochemistry, in situ hybridization and immuno-histochemistry. Neurons expressing NOS mRNA completely overlapped with NADPH-diaphorase-positive neurons. Topographical distribution of NOS was segregated from that of CRF-containing parvicellular neurons in the posterior paraventricular nucleus but overlapped with that of magnocellular neurons. In the paraventricular nucleus, 70% of oxytocin neurons contained NOS, which corresponded to one half of NOS neurons. About one third of vasopressin-immunoreactive neurons were NADPH-diaphorase-positive and the same proportion of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. In the supraoptic nucleus, 50% of oxytocin neurons were NADPH-diaphorase-positive, which corresponded to 40% of NOS neurons. About 25% of vasopressin neurons were NADPH-diaphorase-positive, and 30% of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. When NADPH-diaphorase histochemistry was performed first, subsequent immunostaining was markedly perturbed. Using fluoro-gold as a retrograde tracer, 4% of NADPH-diaphorase-positive neurons were shown to contribute to the descending projection to the spinal cord. About 40%-50% of NADPH-diaphorase-positive neurons exhibited Fos immunoreactivity after injection of lipopolysaccharide or hypertonic saline, while only 10%-15% of these neurons expressed Fos in response to immobilization or pain. Endogenous NO may be involved in the regulation of magnocellular functions, especially when the internal environment is disturbed.

Animals↗
PubMed1996

Expression of fos family and jun family proto-oncogenes during corneal epithelial wound healing.

PURPOSE: While transformation of epithelial cells to a motile form is the first step in wound healing of the corneal epithelium, the migratory mechanism in these cells is not fully understood. We studied the expression of proto-oncogene mRNAs: c-fos; c-jun; fos B; jun B; jun D in injured corneal epithelium using in situ hybridization. Moreover, we examined immunolocalization of c-Fos and c-Jun protein products to elucidate the transcriptional activation prior to the onset of migration in corneal epithelium. METHODS: An epithelial defect was made on one cornea of 60 Wistar rats. The affected eye was enucleated immediately (within 5 min) or was allowed to heal for 15, 30, 60, 90, 120 and 180 min. Frozen sections were processed for in situ hybridization with c-fos, c-jun, fos B, jun B and jun D mRNAs or were stained with anti-c-fos and anti-c-jun antibodies. RESULTS: Fifteen min after the epithelial ablation, weak signals for c-fos and c-jun mRNAs were detected in the corneal epithelium surrounding the wound. These signals reached a peak 30 to 60 min after ablation, but were no longer evident at 120 min. Immunoreactivities for these proteins were also detected in the same area at 60 to 120 min after the epithelial ablation. Fos B mRNA was detected in the same region at 30 min after the ablation, and reached its peak after 30 to 60 min, but was no longer evident at 120 min. Jun B mRNA was detected in the epithelium around the defect 60 min after the ablation, later than the other proto-oncogenes, and reached its peak after 90 min. The message for jun D was detected in normal epithelium, and was not affected by wounding. CONCLUSIONS: These findings indicate that transcriptional activation of epithelial cells is initiated in the early phase after epithelial ablation, before the cells start to migrate, and that these proto-oncogene products may play important roles in wound healing in corneal epithelium. The time lag of the peak of expression of these proto-oncogenes in this process.

Animals↗
PubMed1996

[Molecular mechanisms of chronic pain].

Peripheral noxious stimuli or tissue injury induce the release of excitatory amino acids (EAAs) and other neurotransmitters from primary afferent terminals in the spinal dorsal horn, which may lead to the expression of immediate early genes (IEGs) in dorsal horn neurons via activation of intracellular messengers including Ca2+ and various protein kinases. Various IEGs of fos, jun, and zinc finger families are differentially expressed in dorsal horn neurons in a time dependent manner. Protein products of these genes function as transcription factors and trigger long-lasting plastic changes in CNS neurons. Simultaneously, EAAs may activate the synthesis of prostanoids and NO, which may affect the sensitivity of dorsal horn neurons. In addition, peripheral chemical mediators such as 5-HT contribute to the peripheral hyperalgesia. These events may contribute to the establishment of persistent pain and hyperalgesia in a concerted manner. It is shown that pre-treatment, but not post-treatment, with local anesthetics or analgesics reduces expression of c-fos in spinal cord neurons and pain responses in animals, suggesting that the inhibition of intracellular events by pre-treatment with anesthetics and analgesics is effective for the reduction of persistent pain following tissue injury.

Animals↗
PubMed1995

Effects of local anaesthesia on formalin-induced Fos expression in the rat dorsal horn.

A subcutaneous injection of formalin into foot pad of the rat produces a bimodal nociceptive response including an early intense response in the first 5 min and a later moderate response that is exhibited from 20 to 60 min after injection. In this study, we investigated the effects of blocking the early phase and late phase input, respectively, on Fos-like immunoreactivity (Fos-LI) expression in dorsal horn neurones. Rats of the early phase block (EB) group were injected with 5% formalin (0.05 ml) into the footpad 5 min after a s.c. injection of 4% lidocaine (0.15 ml) into the angle. The rats of the late phase block (LB) group were injected with 5% formalin into the footpad 10 min before the s.c. injection of 3% prilocaine (0.20 ml) containing felypressin into the ankle. The rats of the control group were given the formalin injection alone. Fos-LI was detected in the dorsal horn 2 h after the formalin injection. The numbers of Fos-LI neurones in the dorsal horn of both EB and LB group were markedly decreased compared with the control group, being 31.3% (laminae I-III of EB), 37.1% (laminae I-III of LB), 13.9% (laminae IV-VI of EB) and 16.2% (laminae IV-VI of LB) of the control values. No significant difference was observed between EB and LB group. These findings suggested that the early and late phase contribute in concert to the induction of genetic changes in dorsal horn neurones after formalin injection.

Anesthesia, Local↗
PubMed1995

A relationship between substance P receptor and retinal fibers in the rat suprachiasmatic nucleus.

The suprachiasmatic nucleus (SCN) in the hypothalamus controls many of the circadian rhythms in mammalian species. In the present study, we investigated the location of substance P receptor (SPR)-containing neurons in the rat SCN, using a specific antibody against SPR, which corresponds to the NK-1 subtype of tachykinin receptors, and also examined the synaptic relationship between SPR-containing neurons and retinal fibers at the ultrastructural level. An SPR-immunoreactive meshwork of labeled somata and dendrites was identified in the SCN. The strongest SPR-immunoreactivity was observed in the dorsal and lateral parts of the SCN. Many labeled somata were identified there and their dendrites protruded ventrally from their somata. A few SPR-immunoreactive somata were observed also in the ventral part of the SCN and within the optic tract. In the SCN of eye-enucleated animals, degenerating retinal fibers were shown to terminate on SPR-immunoreactive dendrites forming asymmetrical axo-dendritic contacts.

Animals↗
PubMed1995

Localization of myogenin, c-fos, c-jun, and muscle-specific gene mRNAs in regenerating rat skeletal muscle.

It has been suggested that myogenin is an important factor for the differentiation of myoblasts and that its function in myogenesis is regulated by proto-oncogenes in in vitro experiments. We have characterized the spatial and temporal expression patterns of myogenin, c-fos, c-jun, and muscle creatine kinase mRNAs during the skeletal muscle regeneration process using in situ hybridization histochemistry. Myogenin transcripts are first detected in the myonuclei/nuclei of satellite cells at 6 h after induction of regeneration. Myogenin mRNA is expressed in desmin-positive myoblasts, yet no muscle creatine kinase mRNA is detected in this cell type. Both the muscle creatine kinase and myogenin mRNAs are expressed in the newly formed myotubes, but not at earlier stages. Transcripts for c-fos and c-jun mRNAs are expressed first in the myonuclei/nuclei of satellite cells at 3 h post-trauma. c-jun mRNA is expressed in both myoblasts and myotubes, while c-fos mRNA was not detected in these cells. These results suggest that myogenin plays important role in the regeneration of injured muscle and that c-jun and c-fos may have different roles in this process.

Animals↗