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Mitsuhiro Yoshioka

Publications and source records attributed to Mitsuhiro Yoshioka.

At least 19 recordsLinked to original sources
PubMed2006

Electrophysiological and neurochemical characterization of the effect of repeated treatment with milnacipran on the rat serotonergic and noradrenergic systems.

The present study was undertaken to elucidate the effects of repeated treatment with milnacipran, a serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor (SNRI), on the synaptic plasticity in the hippocampal CA1 field, focusing on the interaction between the serotonergic and noradrenergic system. Repeated treatment with milnacipran (30 mg/kg, i.p. after 30 mg/kg, p.o. x 14 days) completely restored the suppression of the long-term potentiation (LTP) induced by single milnacipran treatment (30 mg/kg, i.p.). Single and repeated milnacipran increased to a similar extent extracellular NA in the hippocampus. Single milnacipran increased extracellular 5-HT and this effect tended to be enhanced by repeated treatment. The restoration of LTP and facilitation of the 5-HT level were not shown after repeated treatment with a selective 5-HT reuptake inhibitor (SSRI) fluvoxamine (30 mg/kg, p.o. x 14 days). These results suggest that milnacipran-induced restoration of LTP suppression is responsible for the enhancement of 5-HT neurotransmission, which appears to be associated with noradrenergic neuronal activity. In addition, the 5-HT1A receptor agonist tandospirone-induced suppression of LTP was completely blocked by repeated treatment with milnacipran, indicating the possibility that this reversal effect is due to the functional changes in postsynaptic 5-HT1A receptors. Taken together, the present data suggest that the interaction between the serotonergic and noradrenergic mechanism play an important role in the modulation of synaptic plasticity caused by repeated treatment with milnacipran, which may be implicated in the therapeutic effects of SNRI on psychiatric disorders.

Adrenergic Uptake Inhibitors↗
PubMed2006

[To know is to relieve; "lifestyle-related diseases"; as they are now and how to prevent them].

Hypertension, diabetes mellitus, hyperlipidemia and obesity have recently defined as lifestyle-related diseases. A common background of these lifestyle-related disease is nutritional excess and its consequence, obesity. Recent advances in the biology of adipose tissue have revealed that adipose is not simply an energy storage organ but it also secretes a variety of molecules which affect the metabolism of the whole body. Dysregulation in the secretion of these adipose-specific secretory proteins may have important roles in the lifestyle-related diseases. It may be a great concern for many people to know about lifestyle-related diseases and how to manage and prevent them. The purpose of this citizen joint symposium is to broaden citizen's knowledge on the mechanism and appropriate management of lifestyle-related disease. We hope that this symposium provide useful informations to the participants about the current information in the management of lifestyle-related diseases.

Adipose Tissue↗
PubMed2005

Temporal effects of edaravone, a free radical scavenger, on transient ischemia-induced neuronal dysfunction in the rat hippocampus.

We examined the effect of a free radical scavenger edaravone on ischemia/reperfusion-induced impairment of long-term potentiation in the perforant path-dentate gyrus synapses of the rat hippocampus, as a measure of functional outcome 4 days after transient global ischemia (2-vessel occlusion, 10 min). Edaravone (3 and 10 mg/kg, i.v.) immediately after reperfusion (Day 0) alleviated ischemia-induced impairment of long-term potentiation in a dose-related manner, whereas treatment on Day 1 or 4 after reperfusion failed to rescue the impaired long-term potentiation. Edaravone administration on Day 0 also prevented the post-ischemic increase in hydroxyl radical formation and the expression of vascular endothelial growth factor, basic fibroblast growth factor and neuronal and inducible nitric oxide synthases of the hippocampus. Thus, edaravone protected the rat hippocampus from ischemia-induced long-term potentiation impairment with a therapeutic time window, suggesting that free radical formation after ischemia/reperfusion is a pivotal trigger of neurofunctional complications after global ischemic stroke.

Animals↗
PubMed2005

Early postnatal stress alters the 5-HTergic modulation to emotional stress at postadolescent periods of rats.

Several lines of evidence have shown that traumatic events during the early postnatal stage might precipitate long-lasting alteration in the functional properties underlying emotional expression. The aim of the present study was to examine whether the early postnatal stress alters the 5-HTergic mechanism underlying regulation of emotional stress, focusing on the 5-HT(1A) receptor-mediated synaptic responses in adult rats. Pups were exposed to aversive stimulus, footshock (FS) at the postnatal period of the second (2W) and the third week (3W). At postadolescent period (10-12-week-old), electrophysiological and behavioral studies were performed. The 5-HT(1A) receptor agonist tandospirone (10 mg/kg body wt, i.p.) blocked the long-term potentiation (LTP) in the hippocampal CA1 field of 3W-FS, as well as non-FS control, whereas this inhibition was not observed in 2W-FS group. Fear-related freezing behavior observed during exposure to contextual fear conditioning markedly attenuated in 2W-FS, but not in 3W-FS. These data suggest that aversive stress exposed at 2W is attributable to changes in the 5-HT(1A) receptor-mediated synaptic plasticity, which may be responsible for the attenuation of freezing behavior. Thus, 5-HT(1A) receptors appear to play a key role in the 5-HTergic mechanism underlying regulation of emotional stress on the postnatal development of the brain. In other words, the second postnatal week may be the "critical period" for establishing proper behavioral responses to emotional stress in adult rats. (c) 2005 Wiley-Liss, Inc.

Aging↗
PubMed2005

Cortical GABAergic regulation of dopaminergic responses to psychological stress in the rat dorsolateral striatum.

The present study was undertaken to examine the possible involvement of cortical gamma-aminobutyric acid (GABA) neuronal mechanisms in the regional differences of dopamine (DA) response to psychological stress: contextual fear conditioning (CFC) in the rat prefrontal cortex (PFC) and dorsolateral striatum (DLS). Rats that received five footshocks (shock intensity, 0.5 mA; shock duration, 2 sec) were subjected to CFC and dynamic changes in DA and GABA in both PFC and DLS were examined using dual-probe microdialysis. Extracellular levels of DA in the PFC were enhanced during exposure to CFC, whereas the levels in the DLS were not affected by this stimulus. Extracellular levels of GABA in the PFC, but not in the DLS, were markedly enhanced by CFC. Freezing behavior observed during exposure to CFC was attenuated by the GABA(A) receptor antagonist bicuculline (10(-3) M), which was perfused into the PFC. Intracortical application of bicuculline (10(-3) M) furthermore caused sustained increases in DA levels in the DLS by CFC. These data suggest that cortical GABA(A) receptors contribute to modulation of DA release in the DLS in response to CFC. Thus, the GABAergic neuronal system in the PFC appears to play a key role in the regional differences of the DAergic response to psychological stress.

Analysis of Variance↗
PubMed2005

Age-related changes in cardiac expression of VEGF and its angiogenic receptor KDR in stroke-prone spontaneously hypertensive rats.

We examined the age-related changes in cardiac expression of angiogenic molecules during the development of cardiac remodeling in stroke-prone spontaneously hypertensive rats (SHRSP) in comparison with those in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Vascular endothelial growth factor (VEGF) was highly upregulated in SHRSP aged 20 weeks compared with the same age of WKY, but it was downregulated at 40 weeks. On the other hand, KDR, an angiogenic receptor of VEGF, and endothelial nitric oxide synthase, which is important in the VEGF-mediated angiogenic pathway, were markedly downregulated in SHRSP from 20 weeks of age. Such age-related changes in their expression levels seen in SHRSP were quite different from those in SHR. In both SHR and SHRSP, transforming growth factor-beta1 (TGF-beta1) expression was increased with age, although SHRSP showed more marked upregulation. Cardiac remodeling in SHRSP was characterized by decreased coronary capillary density, cardiomyocyte hypertrophy, and cardiac fibrosis. We conclude that, in addition to overexpression of TGF-beta1, which appears to play a pivotal role in promoting cardiac hypertrophy and fibrosis, a defect of the VEGF-KDR system could result in impaired physiologic coronary angiogenesis in SHRSP, contributing to cardiac deteroration associated with myocardial ischemia in this malignant hypertensive model.

Age Factors↗
PubMed2005

[Rapidly increasing allergic diseases].

It is well known that allergic diseases, such as allergic rhinitis, asthma, atopic dermatitis, and food allergy, are increasing in prevalence. Epidemiological studies show that the prevalence of allergic diseases is approximately 40% in children and 30% in adult. Thus allergic diseases are global health problem in Japan. Changes in environment or lifestyle may be one of the causes of the increase in allergic diseases. Therefore it may be a great concern for many people how they prevent the diseases or how they manage allergic symptoms. The major purpose of this citizen joint symposium was to broaden citizen's knowledge on the mechanism, epidemiology, and appropriate management of allergic diseases. We hope that this symposium provided useful information to the participants about the current trends in the management of allergic diseases.

Adult↗
PubMed2004

Characterization of regional cerebral blood flow and expression of angiogenic growth factors in the frontal cortex of juvenile male SHRSP and SHR.

Attention-deficit/hyperactivity disorder (AD/HD) is a common pediatric behavioral disorder associated with male preponderance and reduction of regional cerebral blood flow (rCBF). However, lack of an appropriate animal model exhibiting appropriate AD/HD symptoms stands in the way of studying mechanism(s) underlying reduced rCBF and male preponderance. Our group has been investigating the suitability of juvenile male stroke-prone spontaneously hypertensive rats (SHRSP), a substrain of the commonly used AD/HD animal model SHR, as a model for AD/HD because, unlike SHR, SHRSP displays cognitive impairment and male preponderance. Our more recent studies revealed alterations in the synthesis of sex steroid hormones and angiogenic factors in the frontal cortex of male SHRSP compared to the genetic control WKY. Based on these observations, the present study utilizes laser-Doppler flowmetry, histochemistry, enzyme immunoassay, immunoblotting, and real-time PCR to characterize and compare the patterns of regional cerebral blood flow and synthesis of angiogenic molecules [basic fibroblast growth factor; nitric oxide synthase isoforms (endothelial, neuronal and inducible); vascular endothelial growth factor (VEGF) and its signaling molecules (VEGF receptors, phosphorylated Akt, endothelial nitric oxide synthase eNOS] between male SHRSP and SHR. Overall, consistent with our previous data showing alteration in VEGF/Akt/NO signaling, there was a marked reduction in the profile of rCBF (35%) and angiogenic factors of SHRSP, compared to age-matched genetic control Wistar-Kyoto rats (WKY) and SHR. We conclude that, unlike SHR, the profiles of rCBF and angiogenic factors in SHRSP are altered in juvenile male. Thus, SHRSP appears to be a more suitable animal model for studying changes in rCBF in AD/HD.

Age Factors↗
PubMed2004

Chronic treatment with milnacipran reverses the impairment of synaptic plasticity induced by conditioned fear stress.

RATIONALE: Recent studies have focused on neural plasticity at the cellular and molecular levels in the etiology and treatment of stress-related disorders; however, there are no reports concerning modulation of synaptic plasticity in the hippocampus underlying therapeutic effects of antidepressants and/or anxiolytics. OBJECTIVES: To elucidate the functional interaction between the stress-induced alteration of synaptic plasticity and therapeutic effects, we examined the anxiolytic mechanism(s) of milnacipran, focusing on modulation of long-term potentiation (LTP) in the hippocampal CA1 field. METHODS: Rats that received footshock stimulation five times (intensity, 0.5 mA; duration, 2 s; shock interval, 30 s) for 5 days were treated with milnacipran (30 mg kg(-1), p.o.) or vehicle for 14 days. On the 15th day, rats were subjected to conditioned fear stress (CFS) to evaluate freezing behavior. Separate from the behavioral study, electrophysiological approach was performed to evaluate the synaptic efficacy under anesthesia. RESULTS: Exposure to CFS suppressed LTP in the CA1 field. Chronic treatment with milnacipran (30 mg kg(-1), i.p. after 30 mg kg(-1) day(-1), p.o. x14 days), but not acute treatment (30 mg kg(-1), i.p. after vehicle 5 ml kg(-1) day(-1), p.o. x14 days), reduced freezing behavior and reversed the impairment of LTP induced by CFS. CONCLUSION: The present data suggest that a correspondence exists between fear-related behavior and synaptic plasticity in the hippocampus. In other words, anxiolytic mechanism(s) of chronic treatment with milnacipran may be explained by reversal effects on the psychological stress-induced impairment of synaptic plasticity.

Animals↗
PubMed2004

An S-nitrosylated hemoglobin derivative protects the rat hippocampus from ischemia-induced long-term potentiation impairment with a time window.

Evidence suggests that S-nitrosylation is a biological process involved in cerebral ischemia. The aim of the present study was to elucidate the effects of S-nitrosylated (SNO) polyethylene glycol-conjugated (PEG) hemoglobin (Hb) developed as an artificial oxygen carrier, which can absorb free NO and translocate NO to a sulfhydryl (SH) moiety, on ischemic cerebral dysfunction. Long-term potentiation (LTP) in the perforant path-dentate gyrus synapses of the rat hippocampus was evaluated as functional outcome 4 days after transient incomplete cerebral ischemia (2-vessel occlusion: 2VO, 10 min). SNO-PEG-Hb (250 mg/kg, i.v.) administered on Day 0, 1, 2, or 4 (immediately, 24 h, 48 h, or 96 h after reperfusion, respectively) alleviated 2VO-induced LTP impairment with a therapeutic time window. The effect was significant when SNO-PEG-Hb was administered on Day 1 or 2. SNO-PEG-Hb altered NOS features observed in the vehicle-treated 2VO rat, upregulation of eNOS, nNOS, and iNOS expressions at mRNA and protein levels; SNO-PEG-Hb further upregulated eNOS and nNOS and downregulated iNOS expressions. These findings suggest that SNO-PEG-Hb might have protective effects on the rat hippocampus from ischemia/reperfusion-induced functional damages, thereby increasing the therapeutic potential as an artificial oxygen carrier for use in the area of oxygen therapy.

Animals↗
PubMed2004

Serotonergic modulation of psychological stress-induced alteration in synaptic plasticity in the rat hippocampal CA1 field.

In order to elucidate possible involvement of the serotonergic neuronal system in the stress-induced alteration in synaptic plasticity, the effects of contextual fear conditioning (CFC) on long-term potentiation (LTP) in the hippocampal CA1 field were examined in 5-HT-depleted rats by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT, 200 microg/rat, i.c.v.). LTP induction was suppressed by footshock (FS) stimulation in 5-HT-lesioned rats and vehicle-treated controls. When rats were exposed to CFC, which was received 24 h after FS stimulation, LTP was also blocked in both-treated groups. CFC-induced impairment of LTP, however, significantly attenuated in 5-HT-lesioned rats when compared with that in controls. Fear-related freezing behavior after FS stimulation occurred similarly in both treated groups, whereas the behavior observed during exposure to CFC significantly reduced in 5-HT-lesioned rats. These results suggest that the serotonergic mechanism is involved in the psychological stress-induced alteration in synaptic plasticity, which appears to be associated with fear-related behavior.

5,7-Dihydroxytryptamine↗
PubMed2004

Gonadal hormones and frontocortical expression of vascular endothelial growth factor in male stroke-prone, spontaneously hypertensive rats, a model for attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (AD/HD) is a common pediatric behavioral disorder associated, in part, with male preponderance and reduced regional cerebral blood flow (rCBF). However, mechanism(s) underlying male preponderance and reduced rCBF in AD/HD are unclear. The present study profiles the expression of angiogenic and hormonal factors likely to underlie these symptoms using a recently characterized AD/HD animal model, juvenile male stroke-prone spontaneously hypertensive rats (SHRSP). Because vascular endothelial growth factor (VEGF) signaling cascade and gonadal steroids are key regulators of angiogenesis and gender-based behavior, respectively, we profiled their patterns of expression in the frontal cortex of SHRSP to elucidate their roles in the genesis of AD/HD male preponderance and rCBF. Interestingly, levels of VEGF, VEGF receptors (KDR, Flt-1), endothelial nitric oxide synthase, phosphorylated Akt (pAkt), estrogen receptor-alpha, aromatase, and capillary density in sham-operated SHRSP were remarkably down-regulated, whereas androgen receptor levels were up-regulated, compared with age-matched genetic control, Wistar-Kyoto rats. Castration, estrogen, and androgen receptor antagonist (flutamide) counteracted these effects. Dihydrotestosterone, but not testosterone, reversed the beneficiary effects of castration. Estrogen receptor-beta levels remained unchanged in all groups examined. We postulate that changes in androgen metabolism that tend to up-regulate local dihydrotestosterone concentration and diminish estrogen synthesis, in the frontal cortex of juvenile male SHRSP, may lower levels and/or activity of VEGF and its signaling cascade and, subsequently, reduce rCBF. These findings could, in part, help explain the pathogenesis of reduced rCBF and male preponderance in AD/HD.

Animals↗
PubMed2004

Milnacipran, a serotonin and noradrenaline reuptake inhibitor, suppresses long-term potentiation in the rat hippocampal CA1 field via 5-HT1A receptors and alpha 1-adrenoceptors.

Pharmacological characteristics of a serotonin (5-HT) and noradrenaline reuptake inhibitor (SNRI), milnacipran, in modulation of the synaptic plasticity were investigated. Milnacipran (30 mg/kg, i.p.) suppressed the long-term potentiation (LTP) in the hippocampal CA1 field of anesthetized rats. Milnacipran-induced suppression was reversed by pretreatment with the selective 5-HT1A receptor antagonist WAY 100635 (0.1 mg/kg, i.v.) or the alpha1-adrenoceptor antagonist prazosin (1 and 10 microg/rat, i.c.v.). The alpha2-adrenoceptor antagonist idazoxan (5 mg/kg, i.p.) did not influence the milnacipran-induced synaptic responses. These data suggest that the inhibitory effects of milnacipran on LTP induction are mediated via both 5-HT1A receptors and alpha1-adrenoceptors. In other words, functional interaction between the serotonergic and noradrenergic neuronal systems is involved in alteration of the hippocampal synaptic plasticity, which may be implicated in the SNRI-induced therapeutic effect on psychiatric disorders.

Adrenergic Uptake Inhibitors↗
PubMed2004

Effects of acute repetitive transcranial magnetic stimulation on dopamine release in the rat dorsolateral striatum.

Animal studies have shown that descending pathways from the frontal cortex modulate dopamine (DA) release in the striatum. This modulation is thought to be relevant to the pathophysiology of Parkinson's disease. In human, repetitive transcranial magnetic stimulation (rTMS) can result in functional changes in the cortex. The present study intended to clarify the effects of acute rTMS treatment using various stimulation intensities on the extracellular DA concentrations in the rat dorsolateral striatum. The frontal brain of each rat received acute rTMS treatment, which consisted of 500 stimuli from 20 trains in a day. Each train was applied at 25 Hz for 1 s with 1-min intervals between trains. The neurochemical effects of acute rTMS treatment were investigated by determining the extracellular concentrations of DA in the rat dorsolateral striatum using in vivo microdialysis. Acute rTMS treatment of the frontal brain using the stimulation intensity of almost 110% motor threshold (MT) markedly and continuously increased the extracellular DA concentrations in the rat dorsolateral striatum. The present study demonstrates that acute rTMS treatment of the frontal brain affects the DAergic neuronal system in the rat dorsolateral striatum, and may have therapeutic implications for Parkinson's disease.

Analysis of Variance↗
PubMed2004

Effects of endothelin receptor antagonist on expression of AT1 and AT2 receptors in the heart of SHR-SP.

It is already well known that alteration of angiotensin II (Ang II) receptors results in cardiac remodeling in different pathological states, and it is believed that Ang II stimulates the release of endothelin-1 (ET-1). The present study aimed at investigating the interaction between ET-1 and different Ang II receptors in the heart of stroke-prone spontaneously hypertensive rats (SHR-SP). These were treated for 3 months with SB209670, an endothelin-A/endothelin-B dual receptor antagonist, or saline (vehicle) starting from the prehypertensive stage (6 weeks of age). Blood pressure, body weight, heart weight and left ventricular weight were sufficiently decreased after treatment of SHR-SP with SB209670. Ang II type 1 receptor was significantly upregulated in the heart of vehicle-treated SHR-SP compared with the age-matched control, Wistar-Kyoto rat. After endothelin antagonism with SB209670, Ang II type 1 receptor in SHR-SP heart was markedly suppressed. On the other hand, Ang II type 2 receptor was approximately 45% downregulated in the heart of vehicle-treated SHR-SP compared with that of the control, and recovered after endothelin antagonism. The present study demonstrates for the first time the effects of endothelin antagonism on the differential expression and regulation of Ang II receptors in the malignant hypertensive model, SHR-SP, and suggests that the endothelin system may be able to function on the upstream of Ang II signaling.

Angiotensin II↗
PubMed2004

Altered expression of endothelin and its receptors in the brain of SHR-SP at malignant hypertensive stage.

Spontaneously hypertensive stroke-prone rats (SHR-SP) suffer spontaneous stroke in part as a result of abnormal cerebrovascular development. Reduction of regional cerebral blood flow in this model has already been demonstrated. This model has three distinct stages of hypertension: pre-hypertensive, typical hypertensive and malignant hypertensive. We investigated the level of endothelin-1 and its receptor expression in the frontal cortex of SHR-SP at the malignant hypertensive stage (35-40 weeks of age), during which time the rats suffer strokes. The cerebral endothelin-1 level, as determined by enzyme-linked immunosorbent assay, was highly increased at this severely hypertensive stage compared to their genetic control, normotensive Wistar-Kyoto rats. This upregulation was associated with an increased expression of endothelin-A receptor, however, another endothelin-1 receptor, endothelin-B, was downregulated. The regional cerebral blood flow in the frontal cortex was reduced by 60% in 40-week-old malignantly SHR-SP as compared to age-matched Wistar-Kyoto rats. Thus, cerebral endothelin-1 expression increased in malignant hypertension in SHR-SP. The enhanced endothelin-1 may activate the endothelin-A receptor, which would, in turn, result in reduced cerebral blood flow. Downregulation of the endothelin-B receptor may cause suppression of endothelium-derived relaxing factors in the brain of SHR-SP and be an underlying factor in their stroke susceptibility.

Age Factors↗