Biomedical subjects

E Senba

Publications and source records attributed to E Senba.

At least 37 records · Page 2Linked to original sources

PubMed2001

A novel analgesic compound OT-7100 attenuates nociceptive responses in animal models of inflammatory and neuropathic hyperalgesia: a possible involvement of adenosinergic anti-nociception.

We studied the effects of OT-7100 (5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo [1,5-a]pyrimidine), a novel analgesic compound, on the inhibitory action of adenosine on the contraction of guinea pig ileum and investigated the effects of OT-7100 on the nociceptive responses in animal models of inflammatory and peripheral neuropathic hyperalgesia and decreases spinal c-Fos expression. OT-7100 at 0.3 - 3 microM significantly enhanced the inhibitory effect of adenosine on the contraction of guinea pig ileum. The efficacy of OT-7100 (1, 3 or 10 mg/kg, p.o.) on hyperalgesia induced by yeast or substance P and in the Bennett model was significantly suppressed by coadministration of the adenosine A1 antagonist DPCPX (0.01 or 0.1 pmol/animal, i.t.), while OT-7100 without DPCPX significantly increased the nociceptive threshold in each rat model. OT-7100 (3, 10 and 30 mg/kg per day, p.o.) significantly inhibited the mechanical nociceptive threshold in the injured paw in the Chung model. OT-7100 (30 mg/kg, p.o.) significantly decreased the number of Fos-LI neurons in the spinal dorsal horn in the Bennett model. These finding suggest that OT-7100 inhibits hyperalgesia in these animal models possibly by enhancing adenosinergic neurotransmission in the dorsal horn, although we still lack direct evidence for it.

Adenosine↗

PubMed2001

Distinct gene expression in the stomach following stress and alcohol exposure.

Two paradigms of acute stress in the rat were used to produce changes in the stomach. The first involved restraint stress combined with water immersion and the second utilized acute intragastric exposure to absolute ethanol. The mRNA expression of immediate early genes (IEG) such as c-fos, c-jun and NGFI-A, cyclooxygenase (COX)-2 and heat shock proteins (HSP) 70 in the stomach were studied using in situ hybridization histochemistry. Upregulation of IEG and HSP70 mRNAs were observed in the smooth muscle cells of muscularis mucosae, muscularis externa and blood vessels in response to water immersion-restraint stress or intragastric application of absolute ethanol. In the restraint stress model, IEG (c-fos and NGFI-A) mRNAs were induced in the pit and isthmus of the mucosa, while in the ethanol exposure model, IEG (c-fos, c-jun and NGFI-A) and HSP70 mRNAs were upregulated in the damaged epithelium, especially surrounding the deep erosions. COX-2 mRNA was detected in surface mucous cells under desquamation. These distinct gene expressions in the mucosa indicate that the two stress paradigms produce different cellular responses. These data provide new insights into cellular mechanisms that occur during the pathogenesis of acute gastric mucosal lesions.

Alcohol Drinking↗

PubMed2000

Delayed expression of somatostatin mRNA in GDNFs-dependent rat sensory neurons during postnatal development.

Gene expression of somatostatin (SST) and preprotachykinin A (PPTA) in lumbar DRG neurons of postnatal developing rats was examined by in situ hybridization. SST mRNA signals were not seen in DRG neurons until postnatal day 1 to 7, and were detected in about 10% of DRG neurons of 2- and 8-week-old rats. The positive neurons expressed c-ret mRNA in 8-week-old rats. On the other hand, PPTA mRNA signals were constantly seen in about 30% of DRG neurons. This study demonstrates the differential expression patterns of SST and PPTA mRNAs in DRG neurons of developing rats.

Animals↗

PubMed2000

A novel low-density lipoprotein receptor-related protein mediating cellular uptake of apolipoprotein E-enriched beta-VLDL in vitro.

We report here the identification of a novel member of the low-density lipoprotein receptor (the LDL receptor) family through signal sequence trap screening of a mouse lymphocyte cDNA library. The protein was termed LDL receptor-related protein 9 (LRP9). LRP9 is a type I membrane protein predicted to contain 696 amino acids with a calculated molecular mass of 74 764 Da. The NH(2)-terminal half of LRP9 contains two CUB domains separated by a single ligand-binding repeat. The second CUB domain is followed by a cluster of three additional ligand-binding repeats and a transmembrane domain. The COOH-terminal intracellular region contains a proline-rich region. LRP9 mRNA was expressed in the liver, kidney, lung, and heart at high levels, and in the spleen and brain at low levels. In situ hybridization analysis of mouse liver, kidney, and brain detected LRP9 transcripts in hepatocytes, sinusoidal lining cells, peritubular capillaries, choroid plexus, ependyma of the third ventricle, pia matter, and hippocampus. In particular, high levels of expression were observed in the vascular walls. Apolipoprotein E (apoE)-enriched beta-VLDL stimulated cellular cholesteryl ester formation in ldl-A7/LRP9. These results raise the possibility that this newly identified receptor, which is expressed in the liver, may play a physiological role in the uptake of apoE-containing lipoproteins.

Adult↗

PubMed2000

Electrophysiological and morphological characteristics of nucleus tractus solitarii neurons projecting to the ventrolateral medulla.

Electrophysiological and morphological properties of a direct projection from the nucleus of the tractus solitarius (NTS) to the ventrolateral medulla (VLM) were investigated. NTS neurons projecting to the VLM exhibit a monosynaptic excitatory response followed by an inhibitory one after the tractus solitarius stimulation. These neurons show spontaneous inhibitory postsynaptic currents, and have medium to large soma (14-26 microm in diameter). It is concluded that the projection from the NTS to the VLM is mediated mostly by medium to large neurons that are inhibited locally by GABAergic interneurons within the NTS.

Action Potentials↗

PubMed2000

Spontaneous synaptogenesis in ex vivo sympathetic ganglion and the blockade by serum treatment.

Central denervation for more than 1 month has been shown to cause an increase in the number of adrenergic synapses in sympathetic ganglia in vivo. Here, we report several lines of evidence that adrenergic synapses may be generated de novo in ex vivo superior cervical ganglion (SCG) of adult rats only several hours after the isolation. Structures immunoreactive for synaptophysin, a marker of presynaptic elements, were drastically decreased 6 days after the preganglionic denervation. A significant increase in number of synaptophysin positive boutons was observed over 3-8 hours in the denervated SCGs maintained ex vivo at 36 degrees C in oxygenated physiologic saline, and this increase was blocked by adding normal serum in the saline. Electron microscopic analysis confirmed that the number of adrenergic synapses specifically labeled with 5-hydroxydopamine was increased by several-fold under the same condition. Intracellular labeling of SCG neurons revealed an increase in the incidence (from 8 to 50%) of neurons having dendritic plexus after the in vitro incubation. No evidence of axonal sprouting within the ganglion was observed. Intracellular recordings from single neurons of denervated SCGs revealed that maximum amplitudes of inhibitory postsynaptic potentials, which were completely blocked by yohimbine, an alpha2-adrenoceptor antagonist, in response to focal stimulation were increased over the several hours. These results suggest that dendrites of SCG neurons rapidly develop and exhibit local efferent characteristics that underlie the inhibitory synaptic transmission once they are subjected to serum deprivation.

Animals↗

PubMed2000

TROY, a newly identified member of the tumor necrosis factor receptor superfamily, exhibits a homology with Edar and is expressed in embryonic skin and hair follicles.

In a signal sequence trap screening of the murine brain, we identified a new member of the tumor necrosis factor receptor superfamily designated TROY. TROY is a type I membrane protein of 416 amino acids with characteristic cysteine-rich motifs in the extracellular domain and a tumor necrosis factor receptor-associated factor (TRAF) 2 binding sequence in the cytoplasmic domain of 223 amino acids. In fact, activation of nuclear factor kappaB was induced by the overexpression of TROY and inhibited by dominant negative forms of TRAF2, TRAF5, and TRAF6, indicating that TRAFs and nuclear factor kappaB are involved in the signal transduction of TROY. We also cloned a cDNA for a human counterpart, which showed a 75% homology with mouse TROY at the amino acid level. The extracellular domain of TROY exhibits an extensive homology with that of Edar, a receptor that specifies hair follicle fate. TROY mRNA is strongly expressed in brain and embryo and moderately expressed in the heart, lung, and liver but not the spleen. In the embryo, the expression level is particularly strong in the skin. Interestingly, in situ hybridization analysis of the embryo showed that TROY mRNA was exclusively expressed in the epithelium of many tissues. On the other hand, in neonatal mice, TROY is expressed in hair follicles like Edar as well as in the cerebrum, suggesting pleiotropic functions of TROY in development as well as in the adult mice. The Troy gene is located near the waved coat (Wc) locus, a mutant related to abnormalities in skin and hair.

Amino Acid Sequence↗

PubMed2000

The effects of binocular suture and dark rearing on the induction of c-fos protein in the rat visual cortex during and after the critical period.

It has been demonstrated in kittens that binocular lid suture has more deleterious and irreversible effects on plasticity of the developing visual system than rearing in complete darkness. The present study using immunocytochemistry focuses on the effects of the two types of visual deprivation on the inducibility of c-fos protein in visual cortical neurons of rats. Rats were subjected to binocular suture or dark rearing for 1 week during (postnatal days 14-21; P14-P21) and after (P50-P57) the critical period for activity-dependent modifiability of cortical ocular dominance. In rats of both age groups reared in the normal light-dark condition, only a small number of Fos-immunoreactive neurons was obtained in the visual cortex. By contrast, in dark-reared pups and adult rats, numerous c-fos neurons were detected in the layers II-IV and VI of the visual cortex following a brief light exposure (1 h). In rats of both ages subjected to binocular suture, Fos neurons were detected in the same layers as in the dark-reared rats, but significantly less in number. We speculate that the reduced plasticity of the visual cortex in the rats subjected to binocular suture may be due partly to the repressed AP-1 activity in visual cortical neurons. No significant difference was detected in c-fos expression in the visual cortex between visually manipulated pups and adult rats.

Aging↗

PubMed2000

Postnatal differentiation of local networks in the nucleus of the tractus solitarius.

Whole-cell voltage-clamp recordings from rat brain slice preparation were used to investigate a possible developmental change in the patterns of synaptic interactions among the nucleus tractus solitarii neurons by analysing spontaneous postsynaptic current activity. Three types of patterns of spontaneous postsynaptic current activity were distinguished in the nucleus tractus solitarii neurons which showed high activities in terms of current frequency and amplitude. The first type was characterized by the presence in an individual cell of high frequencies and large amplitudes of both spontaneous glutamatergic and GABAergic postsynaptic currents, and observed exclusively in postnatal day 0-7 rats. The second and third types of cells showed predominant either inhibitory or excitatory postsynaptic currents, respectively. After postnatal day 5, nucleus tractus solitarii neurons with high background activity were shown to differentiate into either the second or the third type, with the latter of about 70% in the adult caudal/intermediate nucleus tractus solitarii. Axon collaterals of some medium to large neurons seemed to be decreased by pruning during postnatal development. The early postnatal differentiation of background synaptic activity observed in the nucleus tractus solitarii presumably reflects the local network reorganization and may be related to maturational changes in cardiovascular and respiratory functions.

Animals↗

PubMed2000

Expression of interleukin-6 receptor, leukemia inhibitory factor receptor and glycoprotein 130 in the murine cerebellum and neuropathological effect of leukemia inhibitory factor on cerebellar Purkinje cells.

Expression of glycoprotein 130 and the related receptors, including interleukin-6 receptor and leukemia inhibitory factor receptor, was examined in the murine cerebellum at the protein level. Western blot analysis revealed that interleukin-6 receptor, leukemia inhibitory factor receptor and glycoprotein 130 were expressed in the murine cerebellum. Immunoreactivities for interleukin-6 receptor, leukemia inhibitory factor receptor and glycoprotein 130 were strongly localized on the cell body of Purkinje cells, indicating that both interleukin-6 and leukemia inhibitory factor could act directly on Purkinje cells in murine adult mice. The expressions of interleukin-6 receptor, leukemia inhibitory factor receptor and glycoprotein 130 were observed on the cell membranes of Purkinje cells by immunoelectron microscopy. Immunoreactivity for the interleukin-6 receptor was also detected in the cytoplasm of Purkinje cells. Injection of a murine hemopoietic cell line, FDC-P1 cells, transfected with the complementary DNA encoding the leukemia inhibitory factor led to a reduction in calbindin-positive dendrites of the Purkinje cells.The present results suggest that the leukemia inhibitory factor affects cerebellar functions through Purkinje cells.

Animals↗

PubMed2000

Expression of immediate early genes, HSP70, and COX-2 mRNAs in rat stomach following ethanol ingestion.

The aim of this study was to show the temporal and spatial molecular responses in the rat stomach that follow absolute ethanol-induced acute mucosal injury. Intense signals for immediate early genes (IEG)/transcriptional factors such as c-fos, c-jun, and nerve growth factor-induced gene-A (NGFI-A) mRNAs were observed in the superficial mucosa and in the blood vessels from 15 min to 6 hr after administration, peaking at 15-30 min. Signals for heat shock protein (HSP) 70 mRNA were also detected in the superficial mucosa, in the fibroblasts around gastric erosions, and in the blood vessels from 15 min to 6 hr (peak at 1-2 hr). The signals for cyclooxygenase-2 (COX-2) mRNA were up-regulated in the surface mucous cells that surround the erosions from 30 min to 6 hr (peak at 60-90 min). These findings suggest that IEG, HSP70, and COX-2 are involved in gastric mucosal restitution in different ways.

Alcohol Drinking↗

PubMed2000

Sequential mRNA expression for immediate early genes, cytokines, and neurotrophins in spinal cord injury.

In this communication, we demonstrate the sequential expression of endogenous molecules, including immediate early genes (IEGs), cytokines, neurotrophins, and neurotrophin receptors in the injured spinal cord. In the acute phase, expression of IEGs and cytokines mRNAs were rapidly upregulated within 1 h in nonneuronal cells in the lesioned sites and the surrounding spinal white and gray matter. Maximal expression was observed at 1 h for c-fos and TNF-alpha mRNAs, at 3 h for c-jun and IL-6 mRNAs, and at 6 h for IL-1 beta mRNA, and these signals were virtually nondetectable after 6-12 h from the onset of the injury. Some of these genes products may promote the degeneration of damaged cells and tissues, while others may be involved in the subsequent repair processes. In the subacute phase, expression of NGF, BDNF, NT-3, p75LNGFR and Trk B mRNAs began to increase in the nonneuronal cells and neuronal cells from 6 h, and peaked at 24-72 h in the area where expression of mRNAs for IEGs and cytokines overlapped. Signals for IL-6 mRNA were also observed in motoneurons at 24-72 h after the injury, with the suggestion that these molecules may be involved in promoting axonal sprouting in the injured spinal cord. Of further interest was the finding that this upregulation of IL-1 beta, BDNF, and NT-3 mRNAs in injured spinal cord was attenuated by treatment with high dose glucocorticoids, with the suggestion that the downregulation of BDNF and NT-3 might be disadvantageous to survival and axonal sprouting of spinal neurons.

Animals↗

PubMed2000

Gene expression of receptors for IL-6, LIF, and CNTF in regenerating skeletal muscles.

The biological actions of interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and ciliary neurotrophic factor (CNTF) are mediated via respective functional receptor complexes consisting of a common signal-transducing component, gp130, and other specific receptor components, IL-6 receptor alpha (IL-6R), LIF receptor beta (LIFR), and CNTF receptor alpha (CNTFR). IL-6, LIF, and CNTF are implicated in skeletal muscle regeneration. However, the cell populations that express these receptor components in regenerating muscles are unknown. Using in situ hybridization histochemistry, we examined spatiotemporal expression patterns of gp130, IL-6R, LIFR, and CNTFR mRNAs in regenerating muscles after muscle contusion. At the early stages of regeneration (from 3 hr to Day 2 post contusion), significant signals for gp130 and LIFR mRNAs were detected in myonuclei and/or nuclei of muscle precursor cells (mpcs) and in mononuclear cells located in extracellular spaces between myofibers after muscle contusion, but IL-6R mRNA was expressed only in mononuclear cells. At Day 7 post contusion, signals for gp130, LIFR, and IL-6R mRNAs were not detected in newly formed myotubes, whereas the CNTFR mRNA level was upregulated in myotubes. These findings suggest that the upregulation of receptor subunits in distinct cell populations plays an important role in the effective regeneration of both myofibers and motor neurons. (J Histochem Cytochem 48:1203-1213, 2000)

Animals↗

PubMed1999

Molecular cloning of a cDNA encoding mouse A15, a member of the transmembrane 4 superfamily, and its preferential expression in brain neurons.

A15, a member of the transmembrane 4 superfamily (TM4SF), was isolated by differential screening of the cDNAs that are preferentially expressed on immature T cells. As a first step in the study of the biological function of the A15 molecule, we isolated cDNAs encoding the entire coding region of mouse A15. Nucleotide sequence analysis of the cDNAs revealed that mouse A15 shares 97% amino acid sequence identity with its human counterpart. The mouse A15 protein product has not yet been characterized, but is predicted to be 244 amino acids with four hydrophobic domains. Northern blot analysis of the RNA samples from various mouse tissues disclosed that the A15 transcripts are expressed most strongly in the brains, and are detectable in the colon, muscle, heart, kidney, and spleen. In situ hybridization of the mouse brain with ribo-probe established that the A15 transcripts are expressed primarily in neurons of the frontal cortex, olfactory bulb, dentate gyrus, caudoputamen, and CA3 region of the hypothalamus as well as in Purkinje cells in the cerebellar cortex, which strongly suggests that A15 may have a special function in the fundamental neuronal functioning of the higher nervous system.

Amino Acid Sequence↗

PubMed1999

Up- and down-regulation of BDNF mRNA in distinct subgroups of rat sensory neurons after axotomy.

Anterograde transport of BDNF is enhanced by axotomy in the rat sciatic nerve. However, the changes in BDNF gene expression in dorsal root ganglion (DRG) neurons after axotomy are not known. We examined this issue using in situ hybridization histochemistry. BDNF mRNA was detected in 35-40% of DRG neurons (L5) of control rats. Most of these neurons are small. BDNF gene expression in these neurons was down-regulated after application of capsaicin to the sciatic nerve. Transection of the sciatic nerve induced the up-regulation of BDNF mRNA. The intensely labeled neurons were mainly large and immunoreactive for neuropeptide Y. These results suggest that up- and down-regulation of BDNF gene expression in distinct subgroups of rat DRG neurons are caused by damage to the peripheral nerve.

Afferent Pathways↗

PubMed1999

Postnatal development of NK1, NK2, and NK3 neurokinin receptors expression in the rat retina.

The biological effects of tachykinins are mediated by three distinct receptors, the neurokinin 1 receptor (NK1-R), NK2-R, and NK3-R. There is no information available concerning the development of these receptors in the retina. In the present study, we investigated the localization of tachykinin receptors, using antisera directed against NK1-R, NK2-R, and NK3-R in the adult and developing rat retinas. Numerous NK1-R immunoreactive (NK1-R IR) cells were already observed in the proximal part of the neuroblastic layer in the retina at postnatal day 5 (P5). The distribution and intensity of NK1-R IR cells and processes in the inner nuclear layer (INL) and inner plexiform layer (IPL) at P10 were similar to those of adult retina. Most NK1-R IR cells located in the proximal part of INL, which were morphologically amacrine cells. In the contrast to the early expression of NK1-R IR cells, no NK3-R IR structures existed in the neuronal elements of the retina until P10. NK3-R IR processes were first detected in the outer plexiform layer (OPL) at P10. At P15, NK3-R IR somata were slightly stained in the distal and middle parts of the INL, and NK3-R IR processes were present in the OPL and the upper part of the IPL. During P15-P30, the number of NK3-R IR somata located in the INL remarkably increased. These NK3-R IR cells were morphologically bipolar and amacrine cells. This study provides differential cellular distribution of NK1-R IR cells and NK3-R IR cells in the INL of the rat retina. Our findings suggest that NK1-R and NK3-R are involved in different visual circuits and retinal maturation, and NK3-R may play previously unknown important roles in the visual processes of the rat.

Aging↗

PubMed1999

Systematic expression of immediate early genes and intensive astrocyte activation induced by intrastriatal ferrous iron injection.

The potential role(s) of transitional metals such as iron have been implicated in neurodegeneration through biochemical processes, particularly oxidative stress. We injected ferrous chloride (FeCl2) and ferric chloride (FeCl3) into the striatonigral system of Sprague-Dawley rats to investigate the biological and toxic effects of ferrous iron in the central nervous system. When FeCl2 was injected into the ventral midbrain, rats showed a characteristic behavior which indicated ipsilateral dopaminergic hyperactivity. FeCl2 injection into the striatum induced a dose-dependent damage, the activation of astrocytes and recruitment of macrophage/microglia at the injected site. Interestingly, the activation of astrocytes was also observed in the anatomically remote areas such as the ipsilateral subthalamic nucleus and pars reticulata of the substantia nigra after 1 week. Expression of immediate early genes (IEGs; c-fos and NGFI-A) was observed in the cortex, thalamic nuclei, subthalamic nucleus, pars reticulata of the substantia nigra, lateral and medial geniculate bodies on the ipsilateral side from 3 to 15 h after FeCl2 injection. Pre-treatment with dimethyl sulfoxide, a hydroxyl radical scavenger, prevented FeCl2-induced expression of IEGs in the thalamic nuclei and geniculate bodies, but not in the cerebral cortex. On the other hand, the effects of FeCl3 were faint and limited on IEGs expression and tissue damage. These results suggest that ferrous iron affects the nervous system vigorously, possibly yielding free radicals such as hydroxyl radicals, and could be one of the important candidates for neurodegenerative diseases under the state in which acclimating systems for iron toxicity are disrupted.

Animals↗

PubMed1999

A possible mechanism of TPA-mediated downregulation of neurotrophin-3 gene expression in rat cultured vascular smooth muscle cells.

We have previously reported that in cultured rat vascular smooth muscle cells (VSMCs), neurotrophin-3 (NT-3) gene expression was suppressed by TPA (12-O-tetradecanoyl phorbol-13-acetate), which induces an AP-1 transcription factor. In the present study, to clarify the mechanism for TPA-mediated downregulation of NT-3 gene expression, effects of cycloheximide and dexamethasone (Dex) on the TPA-mediated downregulation were examined in VSMCs. Pretreatment with cycloheximide, an inhibitor of protein synthesis, or simultaneous treatment with Dex, an inhibitor of AP-1, suppressed the TPA-mediated downregulation of NT-3 gene expression. Furthermore, co-transfection of c-fos and c-jun expression vectors into VSMCs resulted in decrease in the NT-3 gene expression. The present findings suggest that TPA-induced AP-1 de novo synthesis causes the downregulation of NT-3 gene expression in VSMCs.

Animals↗