Biomedical subjects

N Hori

Publications and source records attributed to N Hori.

At least 19 recordsLinked to original sources

PubMed2006

Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK II phosphorylation in rats.

Leptin, an adipocytokine encoded by an obesity gene and expressed in adipose tissue, affects feeding behavior, thermogenesis, and neuroendocrine status via leptin receptors distributed in the brain, especially in the hypothalamus. Leptin may also modulate the synaptic plasticity and behavioral performance related to learning and memory since: leptin receptors are found in the hippocampus, and both leptin and its receptor share structural and functional similarities with the interleukin-6 family of cytokines that modulate long-term potentiation (LTP) in the hippocampus. We therefore examined the effect of leptin on (1) behavioral performance in emotional and spatial learning tasks, (2) LTP at Schaffer collateral-CA1 synapses, (3) presynaptic and postsynaptic activities in hippocampal CA1 neurons, (4) the intracellular Ca(2+) concentration ([Ca(2+)](i)) in CA1 neurons, and (5) the activity of Ca(2+)/calmodulin protein kinase II (CaMK II) in the hippocampal CA1 tissue that exhibits LTP. Intravenous injection of 5 and/or 50mug/kg, but not of 500mug/kg leptin, facilitated behavioral performance in passive avoidance and Morris water-maze tasks. Bath application of 10(-12)M leptin in slice experiments enhanced LTP and increased the presynaptic transmitter release, whereas 10(-10)M leptin suppressed LTP and reduced the postsynaptic receptor sensitivity to N-methyl-d-aspartic acid. The increase in the [Ca(2+)](i) induced by 10(-10)M leptin was two times greater than that induced by 10(-12)M leptin. In addition, the facilitation (10(-12)M) and suppression (10(-10)M) of LTP by leptin was closely associated with an increase and decrease in Ca(2+)-independent activity of CaMK II. Our results show that leptin not only affects hypothalamic functions (such as feeding, thermogenesis, and neuroendocrine status), but also modulates higher nervous functions, such as the behavioral performance related to learning and memory and hippocampal synaptic plasticity.

Animals↗

PubMed2006

Electrophysiological effects of three groups of glutamate metabotropic receptors in rat piriform cortex.

1. The effects of three metabotropic glutamate receptor (mGluR) agonists were tested in two pathways of rat piriform cortex. The group I, II and III mGluR agonists used were RS-3,5-dihydroxyphenenylglycine (DHPG) (10-100 microM), (2S,1'S,2'S)-2-Carboxycyclopropyl (L-CCG) (20-100 microM) and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) (5-500 microM), respectively. 2. The effects of the three groups of agonists on synaptic transmission in the two piriform cortex pathways also were examined. All three agonists reduced the amplitude of the monosynaptic EPSPs generated by stimulation of the lateral olfactory tract (LOT) or of the association fiber pathway (ASSN). This was always accompanied by an increase in paired pulse facilitation. 3. Group I and II mGluR agonists had similar synaptic effects on the two pathways, while the group III mGluR agonist suppressed the LOT pathway more than the association pathway. 4. The group II and III mGluR agonists had no effect on passive membrane properties of pyramidal neurons. Group I agonists depolarized the pyramidal neuron membrane potential, and enhanced both membrane resistance and noise. 5. Our data suggest that all three types of mGluRs modulate synaptic transmission in both of these pathways in piriform cortex. Only group I agonists alter post-synaptic membrane properties, while all three types of receptor regulate synaptic transmission. Groups I and II are equally potent in the LOT and association fiber pathways, while group III receptors are more potent in the LOT than the association fiber pathways.

Amino Acids, Dicarboxylic↗

PubMed2005

Suppression of stress-induced nNOS expression in the rat hypothalamus by biting.

Nitric oxide (.NO) modulates the activity of the endocrine system in the behavioral response to stress. The purpose of this study was to investigate the effect of restraining the body of an animal on expression of neuronal nitric oxide synthase (nNOS) in the paraventricular nucleus (PVN) of the hypothalamus, and the inhibitory effect of para-masticatory activity on restraint-induced nNOS expression. We observed an increase in nNOS mRNA expression and nNOS-positive neurons in the rat hypothalamus after 30 or 60 min of restraint. Biting on a wooden stick during bodily restraint decreased nNOS mRNA expression in the hypothalamus. In addition, the number of nNOS-positive neurons was significantly reduced in the PVN of the hypothalamus. These observations clearly suggest a possible anti-stress effect of the masticatory activity of biting, and this mechanism might be unconsciously in operation during exposure to psychological stressors.

Adaptation, Psychological↗

PubMed2005

Poststreptococcal acute glomerulonephritis superimposed on bilateral renal hypoplasia.

An 8-year-old girl with preexisting chronic renal failure (CRF) due to bilateral renal hypoplasia presented with edema, gross hematuria and acute deterioration of renal function. The diagnosis of poststreptococcal acute glomerulonephritis (PSAGN) was made based on clinical presentation, red blood cell casts, low level of C3 and elevated antistreptolysin 0 titer. Her course was prolonged with serum creatinine increased from the baseline level of 1.1 mg/dl to 2.2 mg/dl, returning toward the baseline level (1.2 mg/dl) after one month. Serum creatinine then started to increase again. The slope of creatinine clearance over time became steeper after the episode of PSAGN. A severe course of PSAGN and subsequent deterioration of renal function have previously been reported in patients with diabetic nephropathy or focal glomerulosclerosis. The present case along with a literature review suggests that individuals with fewer nephrons are at higher risk of severe course and outcome of PSAGN. Conversely, patients with severe PSAGN may be born with fewer nephrons due to low birth weight, unrecognized renal hypoplasia or other unknown causes.

Acute Disease↗

PubMed2004

Biting suppresses stress-induced expression of corticotropin-releasing factor (CRF) in the rat hypothalamus.

Corticotropin-releasing factor (CRF) expressed in the hypothalamus plays an important role in mediating behavioral responses to stressors. Restraining the body of an animal has been shown to activate and induce an enhanced expression of CRF in paraventricular neurons of the rat hypothalamus. Since aggressive biting behavior is known to suppress stress-induced noradrenaline secretion in the central nervous system and the formation of gastric ulcers, we investigated the effect of biting on restraint-induced CRF expression in the rat hypothalamus. The number of CRF-expressing neurons in the paraventricular nucleus increased significantly after short time restraint (30 or 60 min) followed by a 180-minute post-restraint period. Biting of a wooden stick during the restraint stress significantly suppressed the restraint-induced enhancement of CRF expression in the paraventricular nucleus. These observations suggest a possible anti-stress effect of biting and an important role of para-functional masticatory activity in coping with stressful events.

Adaptation, Psychological↗

PubMed2002

Differential actions and excitotoxicity of glutamate agonists on motoneurons in adult mouse cervical spinal cord slices.

Electrical activity was recorded from motoneurons in adult mouse cervical spinal cord (C4-8) slices. Motoneurons showed almost no response to ionophoretic application of N-methyl-D-aspartic acid (NMDA) in both control and Mg(2+)-free media, but very sensitive to kainate (KA) and amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). Bath perfusion of KA, AMPA or glucose/O(2) free Krebs-Ringer solution, but not bath perfusion of NMDA, caused membrane depolarization within 3 min and beading of the dendrite trees after more than 10 min perfusion. Our results indicate that adult motoneurons have few or no NMDA receptors.

Animals↗

PubMed2002

Corticospinal transmission to motoneurons in cervical spinal cord slices from adult rats.

Cervical spinal cord slices were prepared from adult rats. Intracellular recordings from motoneurons revealed that electrical stimulation of the ventralmost part of the dorsal funiculus (which contains primarily descending corticospinal axons) elicited EPSPs in 75% of the neurons. The latencies of these EPSPs tended to be shorter than those elicited by dorsal horn gray matter stimulation. Pairs of subthreshold dorsal funiculus stimuli were able to elicit action potentials in motoneurons. These data are consistent with previous morphological and electrophysiological studies indicating that cervical motoneurons receive both mono-and polysynaptic corticospinal inputs. In addition, motoneurons were markedly depolarized by iontophoretic application of AMPA or KA (7 out of 7 neurons), but only weakly depolarized by NMDA (1 out of 6 neurons). CNQX (but not AP-5) blocked EPSPs elicited by dorsal funiculus stimulation. Thus, corticospinal transmission to motoneurons is mediated primarily by non-NMDA glutamate receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2002

Physiological and anatomical properties of the suprachiasmatic nucleus of an anophthalmic mouse.

Congenitally anophthalmic mice (ZRDCT-AN) have circadian rhythms which 'free-run' and are not light modulated. Their rhythms differ from those of controls in: duration of circadian period, length of active phase, and pattern/intensity of activity. Three different populations have been described based upon wheel-running: rhythmic with stable period, rhythmic with unstable period and arrhythmic. Circadian rhythms are generated by neurons in the suprachiasmatic nuclei (SCN) of the hypothalamus. To better understand whether intrinsic properties of SCN neurons differ in anophthalmic and sighted mice, we examined the electrical activity of these neurons in slices, using single unit recordings, ionophoresis and bath perfusion of agonists and antagonists of known SCN neurotransmitters. Lucifer yellow was injected to characterize morphology. In controls, in daytime, units fired at a higher rate (44% at >/=5 Hz) than at night (21% at >/=5 Hz) and with regular interspike intervals versus irregular intervals nocturnally. In anophthalmics four firing patterns were observed as follows: (1) irregular at <5 spikes/s (70% of the total); (2) regular at >/=5 spikes/s; (<10%); (3) irregular bursts (20%); (4) regular bursts (<1%). Most neurons were inhibited by GABA, but a few were excited in controls. Blocking synaptic transmission with low Ca(2+)/high Mg(2+) increased the frequency and regularized the pattern of previously irregular discharges both in anophthalmics and controls. Bicuculline (10(-5) M), a GABA(A) antagonist, had a similar effect. These data suggest that the characteristic irregular firing pattern of anophthalmics, and of controls at night, results from extrinsic, at least in part, GABAergic input.

Action Potentials↗

PubMed2002

Rat motoneuron cell death in development correlates with loss of N-methyl-D-aspartate receptors.

New techniques were applied for maintaining viable motoneurons in rat cervical spinal cord slices to study electrical and morphological properties from postnatal day (PD) 2-49. Lucifer Yellow injections showed nine to 12, or more, viable motoneurons/slice at PD2, reduced to two to three in lamina IX by PD9. At PD2 and from PD14 onward healthy motoneurons were electrically similar to those of adults. Motoneurons exhibited variable electrical properties and morphology around PD5. They were sensitive to kainate and AMPA at all ages. The sensitivity to N-methyl-D-aspartate (NMDA) was significant at PD2, less at PD9 and virtually absent at PD14. Our observations suggest that NMDA receptors play a role in regulation of motoneuron survival in the early postnatal period, but are lost from adult motoneurons.

Age Factors↗

PubMed2002

Impairment of long-term potentiation and spatial memory in leptin receptor-deficient rodents.

Leptin is well known to be involved in the control of feeding, reproduction and neuroendocrine functions through its action on the hypothalamus. However, leptin receptors are found in brain regions other than the hypothalamus (including the hippocampus and cerebral cortex) suggesting extrahypothalamic functions. We investigated hippocampal long-term potentiation (LTP) and long-term depression (LTD), and the spatial-memory function in two leptin receptor-deficient rodents (Zucker rats and db/db mice). In brain slices, the CA1 hippocampal region of both strains showed impairments of LTP and LTD; leptin (10(-12) M) did not improve these impairments in either strain. These strains also showed lower basal levels of Ca(2+)/calmodulin-dependent protein kinase II activity in the CA1 region than the respective controls, and the levels did not respond to tetanic stimulation. These strains also showed impaired spatial memory in the Morris water-maze test (i.e. longer swim-path lengths during training sessions and less frequent crossings of the platform's original location in the probe test. From these results we suggest that the leptin receptor-deficient animals show impaired LTP in CA1 and poor spatial memory due, at least in part, to a deficiency in leptin receptors in the hippocampus.

Animals↗

PubMed2001

Intracellular activity of rat spinal cord motoneurons in slices.

Using a modification of Aghajanian and Rasmussen's techniques, we have developed an adult rat cervical spinal cord slice preparation in which motoneurons remain viable. Key factors are replacement of all sodium ions in the perfusion medium with sucrose during cutting and incubation, and gentle manipulation of the tissues to prevent root damage during removal. Intracellular recordings were confirmed as motoneuronal by intracellular injection of Lucifer yellow, allowing visualization of dendrites and cell body, and showing an axonal bleb at the cut end in the ventral root. Over 50 neurons were recorded for periods of between 30 min and 4 h. Cervical motoneurons (n=10) had an average membrane potential of -62 mV, average input resistance of 24 M(Omega), and showed no spontaneous activity. Ionophoresis application of the glutamate agonists, AMPA and NMDA, revealed potent excitation by AMPA but little or no response to NMDA. While NMDA receptors reportedly are prominent in developing rodent motoneurons, these observations indicate otherwise in the adult. Upon prolonged ionophoresis, or bath application, depolarizing responses to AMPA led to depolarization and spike inactivation that was often irreversible. The apparent lack of desensitization of AMPA responses, usually seen in other neurons, may underlie the unique vulnerability of motoneurons to excitotoxic damage.

Action Potentials↗

PubMed2001

Effects of acetylcholine and GABA on neurons in the area postrema of Suncus murinus brainstem slices.

Slices (400 microm) containing the area postrema were prepared from three Japanese house musk shrews. Data reported are from 16 representative units. Units fell into one of three separate groups with spontaneous firing rates of 36-41/s, 16-18/sec. and 6-8/sec., possibly reflecting different set points of an endogenous pacemaker. Most neurons did not respond to ionophoresis of GABA or ACh. In those that did, ACh briefly increased spike frequency in a dose-dependent manner. The firing pattern suggests that the membrane potential was depolarized strongly, coupled with an extremely large conductance increase. Bath perfusion of curare, but not atropine, inhibited the response. Ionophoresis of GABA caused strong inhibition. The data show Suncus AP contains neurons that are sensitive to nicotine and GABA and may be emetogenic.

Acetylcholine↗

PubMed2001

Identification of a novel human ankyrin-repeated protein homologous to CARP.

We cloned a novel ankyrin repeat protein, Arpp, by immunoscreening a cDNA library constructed from a human esophageal carcinoma cell line, TE1, with an antibody directed to a hypothetical protein encoded by antisense p53 mRNA. Arpp protein is composed of 333 amino acids and contains four ankyrin-like repeat motifs in the middle portion of the protein, a PEST-like sequence and a lysine-rich sequence similar to a nuclear localization signal in the N-terminal region, and a proline-rich region containing consensus phosphorylation sites in the C-terminal region. Protein sequence analysis revealed that Arpp is homologous (52.7% identity) to Carp which is shown to be involved in the regulation of the transcription of the cardiac ventricular myosin light chain 2 gene. Arpp mRNA was found to be expressed in normal skeletal and cardiac muscle. Interestingly, Arpp expression was detectable in bilateral ventricles, but undetectable in bilateral atria and large vessels, suggesting that Arpp may play a specific function in cardiac ventricles as well as skeletal muscles.

Ankyrin Repeat↗

PubMed2001

Extensive mesenteric vein and portal vein thrombosis successfully treated by thrombolysis and anticoagulation.

Mesenteric vein thrombosis is generally difficult to diagnose and can be fatal. A case of extensive thrombosis of the mesenteric and portal veins was diagnosed early and successfully treated in a 26-year-old man with Down syndrome who was admitted to hospital because of abdominal pain, severe nausea and high fever. Ultrasonography revealed moderate ascites, and there was minimal flow in the portal vein (PV) on the Doppler examination. Computed tomography (CT) showed remarkable thickening of the walls of the small intestine and extensive thrombosis of the mesenteric, portal and splenic veins. Because neither intestinal infarction nor peritonitis was seen, combined thrombolysis and anticoagulation therapy without surgical treatment was chosen. Urokinase was administered intravenously and later through a catheter in the superior mesenteric artery. Heparin and antibiotics were given concomitantly. The patient's symptoms and clinical data improved gradually. After 10 days, CT revealed that collateral veins had developed and the thrombi in the distal portions of the mesenteric veins had dissolved, although the main trunk of the PV had not recanalized. The only risk factor of thrombosis that was detected was decreased protein S activity.

Adult↗

PubMed2001

AILIM/ICOS: its expression and functional analysis with monoclonal antibodies.

Activation-inducible lymphocyte immuno-mediatory molecule (AILIM/ICOS) is the third member of the co-stimulatory molecule CD28/CTLA-4 (CD152) family, and an inducible cell surface glycoprotein expressed on lymphocytes following activation. To determine the expression profile of the molecule, we generated monoclonal antibodies (MAbs) against human, rat, and mouse AILIM/ICOS. None of the MAbs bound to AILIM/ICOS of other species. The numbers of AILIM/ICOS-positive cells among human peripheral blood mononuclear cells (PBMC), and rat and mouse splenocytes were very low (0.5, 0.4, and 1.2%, respectively), and the cells included many CD4-positive T cells except in the case of rat. Rat AILIM/ICOS-positive cells among splenocytes included many CD45RA-positive B cells, although the expression on lymph node cells was similar to that on human PBMC and mouse splenocytes. Among rat thymocytes, the AILIM/ICOS expression was mainly localized on CD4- and CD8-double positive T cells. The binding of AILIM/ICOS to B7h-Ig, which is the ligand-Fc chimeric protein, was inhibited by all AILIM/ICOS-specific MAbs except for SG430. The potency of the co-stimulatory activity of CD3 and AILIM/ICOS as to T-cell proliferation was found to be substantial in human. Interestingly, the levels of stimulation with the two types of MAbs were equal to that with CD3 and CD28 despite the different functions of the two MAbs in the AILIM/ICOS-B7h interaction. On the other hand, the potencies in rat and mouse, although two independent MAbs were tested, were relatively lower than that of CD28-mediated co-stimulation.

Animals↗

PubMed2001

Stimulatory effect of endothelin-1 on neurons in the nucleus tractus solitarii is mediated by non-N-methyl-D-aspartate receptors.

We previously demonstrated that endothlin-1 (ET-1) augments and ETA receptor antagonist attenuates excitatory neuronal response to glutamate (Glu) in brainstem slices from normotensive rats. The aim of this study was to determine which type of Glu receptor is responsible for the stimulatory effects of ET-1 on neurons of the nucleus tractus solitarii (NTS). Single unit discharges were recorded extracellularly from rat brainstem slice preparations. Seven NTS neurons that were excited by solitary tract (ST) stimulation responded to iontophoretically applied ET-1 with neuronal activity. An N-methyl-D-aspartate (NMDA) receptor antagonist, non-NMDA, 6-cyano-7-nitro-quinoxaline-2, 3-dione (CNQX), or DL-2-amino-5-phosphonovaleric acid (AP-5) was perfused over the slices with Kreb's-Ringer solution. The increase in neuronal activity evoked by iontophoretically applied ET-1 was nearly abolished by CNQX but not by AP-5. CNQX but not AP-5 decreased the basal spontaneous neuronal activity of NTS neurons. These results suggest that non-NMDA receptors play a role in mediating the stimulatory effect of ET-1 on neuronal activity in the NTS.

2-Amino-5-phosphonovalerate↗

PubMed2001

Histological study of rat masseter muscle following experimental occlusal alteration.

It has been suggested that occlusal interference results in masticatory muscle dysfunction. In our previous study, occlusal interference reduced the rat masseter energy level during masticatory movements. The purpose of this study was to investigate the histological alterations of rat masseter muscles following experimental occlusal alteration with unilateral bite-raising. A total of eight male adult Wistar rats were equally divided into control and experimental groups. The experimental rats wore bite-raising splints on the unilateral upper molar. However, 4 weeks after the operation, the anterior deep masseter muscles were removed and then stained for succinic acid dehydrogenase (SDH), haematoxylin eosin (HE) and myofibrillar ATPase. Most of the muscle fibres in experimental rats remained intact, although partial histological changes were observed, such as extended connective tissue, appearance of inflammatory cells in the muscle fibres and existence of muscle fibres with central nuclei and central cores. Moreover, the fibre area-fibre frequency histograms of experimental muscle indicated a broad pattern than that of controls. These results indicated that occlusal interference caused histological changes in masseter muscles and that this may be related to the fact that the masseter energy level was reduced during masticatory movements in unilateral bite-raised rats.

Animals↗

PubMed2000

Effect of fatty acid Esters on permeation of ketoprofen through hairless rat skin.

Twelve medium to long chain fatty acid Esters (Esters), the total number of carbon atoms of which ranged from 17 to 34, were used to study the effect of the vehicle on the permeation of ketoprofen, and the effect was compared with the case of indomethacin. The solubility of ketoprofen was higher in Esters with a smaller number of carbon atoms. The permeation rate of ketoprofen from the Ester suspension through excised hairless rat skin was proportional to its solubility in the suspension, which was the same in the case of indomethacin. The diffusion constant and partition coefficient were calculated using the computer program MULTI(FILT). The diffusion constant decreased with increasing number of carbon atoms, and the partition coefficient was increased with increasing number of carbon atoms, in both cases of ketoprofen and indomethacin. Esters also penetrated the skin with the concentration of about 10 mg/g, independent of the number of carbon atoms. The Esters in the skin increase the diffusion rate of the drugs, especially in the case of Esters with a small number of carbon atoms. Also the drug solubility in the skin was improved, although the effect was similar for the range of Esters investigated in the present study. Then the permeation rate of ketoprofen and indomethacin increased.

Animals↗