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Biomedical subjects

H Katsuki

Publications and source records attributed to H Katsuki.

At least 55 records · Page 3Linked to original sources
PubMed1997

Neurotrophic activity of organosulfur compounds having a thioallyl group on cultured rat hippocampal neurons.

Several organosulfur compounds found in garlic extract promoted the survival of rat hippocampal neurons in vitro. From the analysis of structure-activity relationship, thioallyl group in these compounds is essential for the manifestation of neurotrophic activity. S-Allyl-L-cysteine (SAC), one of the organosulfur compounds having thioallyl group in garlic extract, also promoted the axonal branching of cultured neurons. These results suggest that thioallyl compounds make a unique group of neurotrophic factors.

Animals↗
PubMed1997

Noradrenergic regulation of synaptic plasticity in the hippocampal CA1 region.

The effects of norepinephrine (NE) and related agents on long-lasting changes in synaptic efficacy induced by several patterns of afferent stimuli were investigated in the CA1 region of rat hippocampal slices. NE (10 microM) showed little effect on the induction of long-term potentiation (LTP) triggered by theta-burst-patterned stimulation, whereas it inhibited the induction of long-term depression (LTD) triggered by 900 pulses of 1-Hz stimulation. In nontreated slices, 900 pulses of stimuli induced LTD when applied at lower frequencies (1-3 Hz), and induced LTP when applied at a higher frequency (30 Hz). NE (10 microM) caused a shift of the frequency-response relationship in the direction preferring potentiation. The effect of NE was most prominent at a stimulus frequency of 10 Hz, which induced no changes in control slices but clearly induced LTP in the presence of NE. The facilitating effect of NE on the induction of LTP by 10-Hz stimulation was blocked by the beta-adrenergic receptor antagonist timolol (50 microM), but not by the alpha receptor antagonist phentolamine (50 microM), and was mimicked by the beta-agonist isoproterenol (0.3 microM), but not by the alpha1 agonist phenylephrine (10 microM). The induction of LTD by 1-Hz stimulation was prevented by isoproterenol but not by phenylephrine, indicating that the activation of beta-receptors is responsible for these effects of NE. NE (10 microM) also prevented the reversal of LTP (depotentiation) by 900 pulses of 1-Hz stimulation delivered 30 min after LTP induction. In contrast to effects on naive (nonpotentiated) synapses, the effect of NE on previously potentiated synapses was only partially mimicked by isoproterenol, but fully mimicked by coapplication of phenylephrine and isoproterenol. In addition, the effect of NE was attenuated either by phentolamine or by timolol, indicating that activation of both alpha1 and beta-receptors is required. These results show that NE plays a modulatory role in the induction of hippocampal synaptic plasticity. Although beta-receptor activation is essential, alpha1 receptor activation is also necessary in determining effects on previously potentiated synapses.

Afferent Pathways↗
PubMed1997

Furosemide-sensitive calcium rise induced by GABAA-receptor stimulation in cultures of embryonic rat striatal neurons.

Changes in [Ca2+]i induced by gamma-aminobutyric acid (GABA) were investigated in primary cultured neurons obtained from fetal rat striatum. GABA and muscimol induced [Ca2+]i rise, and bicuculline blocked the effect of GABA. The [Ca2+]i elevating effect of GABA was also abolished by removal of extracellular Ca2+ or by application of nicardipine. Furthermore, furosemide, an inhibitor of Na+/K+/ 2Cl- co-transport, reversibly inhibited the GABA-induced [Ca2+]i rise. These results suggest that due to the elevated level of intracellular Cl- maintained by Na+/K+/2Cl- transport activity in these neurons, opening of GABAA-receptor-associated Cl- channels results in Cl- efflux, leading to membrane depolarization and activation of L-type voltage-dependent Ca2+ channels.

Animals↗
PubMed1996

Hydrogen peroxide-mediated neuronal cell death induced by an endogenous neurotoxin, 3-hydroxykynurenine.

3-Hydroxykynurenine (3-HK) is a tryptophan metabolite whose level in the brain is markedly elevated under several pathological conditions, including Huntington disease and human immunodeficiency virus infection. Here we demonstrate that micromolar concentrations (1-100 microM) of 3-HK cause cell death in primary neuronal cultures prepared from rat striatum. The neurotoxicity of 3-HK was blocked by catalase and desferrioxamine but not by superoxide dismutase, indicating that the generation of hydrogen peroxide and hydroxyl radical is involved in the toxicity. Measurement of peroxide levels revealed that 3-HK caused intracellular accumulation of peroxide, which was largely attenuated by application of catalase. The peroxide accumulation and cell death caused by 1-10 microM 3-HK were also blocked by pretreatment with allopurinol or oxypurinol, suggesting that endogenous xanthine oxidase activity is involved in exacerbation of 3-HK neurotoxicity. Furthermore, NADPH diaphorase-containing neurons were spared from toxicity of these concentrations of 3-HK, a finding reminiscent of the pathological characteristics of several neurodegenerative disorders such as Huntington disease. These results suggest that 3-HK at pathologically relevant concentrations renders neuronal cells subject to oxidative stress leading to cell death, and therefore that this endogenous compound should be regarded as an important factor in pathogenesis of neurodegenerative disorders.

Animals↗
PubMed1996

Basic fibroblast growth factor increases functional L-type Ca2+ channels in fetal rat hippocampal neurons: implications for neurite morphogenesis in vitro.

Basic fibroblast growth factor (bFGF) is a potent neurotrophic factor that regulates cell proliferation and differentiation during neuronal development. Here we report that fetal hippocampal neurons chronically treated with bFGF displayed larger [Ca2+]i increases than nontreated neurons in response to high K(+)-induced depolarization. This [Ca2+]i response was abolished by nicardipine and was little affected by treatments that depleted intracellular Ca2+ stores, thus reflecting the activities of L-type voltage-dependent Ca2+ channels. Whole-cell recordings also demonstrated increased high-voltage-activated Ca2+ currents in bFGF-treated neurons, whereas low-voltage-activated Ca2+ currents remained unchanged. bFGF-stimulated increase in Ca2+ response was not observed in neurons treated with cycloheximide or actinomycin D, indicating that protein and RNA synthesis were required for this effect. Visualization using a fluorescent dihydropyridine analog revealed that bFGF-treated neurons expressed increased amounts of L-type Ca2+ channels on the cell body. In addition, bFGF-treated neurons acquired distinctive morphology of neurites that was characterized by markedly increased neuritic branching. The branching points in neurites were associated with clusters of L-type Ca2+ channels and resultant "Ca2+ hotspots" that showed large [Ca2+]i increases in response to membrane depolarization. Concurrent application of nicardipine completely blocked the bFGF-stimulated increase in neuritic branching. Therefore, bFGF enhances the expression of functional L-type Ca2+ channels on the cell body and neurites of fetal hippocampal neurons, which may play an important role in the regulation of their differentiation and the establishment of their neurite morphology.

Animals↗
PubMed1996

Effects of coculture with the septum on the expression of long-term potentiation in organotypic hippocampal slice cultures.

The hippocampus receives major afferent innervation from the septum. Using organotypic slice culture, we investigated whether coculture with the septum would modulate transmission and plasticity of hippocampal synapses. In septo-hippocampal cocultures, acetylcholinesterase-positive fibers extending from septal tissue to hippocampal slice were observed. Septo-hippocampal cocultures exhibited larger magnitude of long-term potentiation (LTP) in CA3 and CA1 synapses than hippocampal slices cultured alone, without significant changes in maximal synaptic responses and macroscopic hippocampal cytoarchitecture. Unexpectedly, the facilitatory effect on hippocampal LTP was independent of afferent innervation from the septum, because (1) electrical stimulation of the cocultured septum suppressed the induction of hippocampal LTP, (2) chronic application of 1 microM atropine did not block the facilitatory effect, and (3) septo-hippocampal cocultures without contact with each other still showed a larger magnitude of LTP than hippocampal slices alone. These results suggest that diffusible factor(s) released from the septal tissue modulate functional maturation of hippocampal synapses as to the ability to support synaptic plasticity.

Animals↗
PubMed1996

Determination of R(+)- and S(-)-lansoprazole using chiral stationary-phase liquid chromatography and their enantioselective pharmacokinetics in humans.

PURPOSE: Stereoselective and sensitive methods employing chiral stationary phase columns for HPLC determination of enantiomers of lansoprazole in the human serum were developed and pharmacokinetic behaviors of the enantiomers were evaluated in seven subjects. METHODS: Five chiral stationary phase columns: Chiralcel OD (cellulose tris(3,5-dimethyl-phenylcarbamate)), OF (cellulose tris(4-chlorophenylcarbamate)), OG (cellulose tris(4-methylphenylcarbamate)) and OJ (cellulose tris(4-methylbenzoate)), and Chiralpak AS (amylose tris ((S)-1-phenylethylcarbamate)) were investigated. RESULTS: Chiralcel OD and Chiralpak AS columns gave a good resolution of R(+)- and S(-)-enantiomers from racemic lansoprazole, but Chiralcel OF, OG, and OJ did not. The mean Cmax and the AUC values of R(+)-enantiomer were 3-5 times greater than those of S(-)-enantiomer following oral administration of 30 mg of racemic lansoprazole. The CLtot values of R(+)-enantiomer were significantly smaller than those of S(-)-enantiomer. Binding of R(+)-enantiomer to human serum proteins was significantly greater than that of S(-)-enantiomer. The mean metabolic ratio (metabolites/parent compound) in human liver microsomes of S(-)-enantiomer was significantly greater than that of R(+)-enantiomer. CONCLUSIONS: The stereoselective pharmacokinetics of lansoprazole enantiomers is likely due to its stereoselective protein binding and/or metabolism.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

3-Hydroxykynurenine toxicity on the rat striatum in vivo.

3-Hydroxykynurenine (3-HK) is a tryptophan metabolite whose level in the brain is elevated under several pathological states including Huntington's disease. In the present study, we examined the possible toxicity of 3-HK by injection of this substance into rat brain. Intrastriatal injection of 3-HK (50 nmol) induced tissue damage around the injected site. Quinolinic acid (QA) at 200 nmol also induced tissue damage, which was comparable in size to that induced by 50 nmol 3-HK. Co-administration of MK-801 significantly reduced QA-induced lesion, but failed to prevent 3-HK-induced lesion. On the other hand, the antioxidant N-acetyl-L-cysteine (10 nmol) reduced 3-HK-induced damage. Thus, 3-HK may be involved in brain pathogenesis by providing oxygen radicals.

Acetylcysteine↗
PubMed1996

[Epidural anesthesia for patients with bronchial asthma].

The choice of epidural anesthesia for patients with bronchial asthma is controversial. We used epidural anesthesia during surgery in 16 cases of asthma. Epidural anesthesia produced by 1% or 2% lidocaine or mepivacaine without epinephrine did not induce asthmatic attack in any patients. After epidural block, general anesthesia was induced with midazolam and vecuronium and endotracheal tube was inserted in 9 patients. Asthmatic attack occurred in two patients. In one patient it occurred by the endotracheal intubation and in another patient during thyroidectomy under nitrous oxide - oxygen - sevoflurane anesthesia, although no attack was observed in 7 patients. Two patients were considered to be in severe state of bronchial asthma and they had been on steroid drug and inhalation therapy before surgery. Both patients recovered soon with antiasthmatic therapy. These results suggest that epidural anesthesia has little or no relevance to asthmatic attack.

Adult↗
PubMed1995

Antioxidants, but not cAMP or high K+, prevent arachidonic acid toxicity on neuronal cultures.

Arachidonic acid (AA) showed profound toxicity against primary neuronal cultures prepared from fetal rat striatum. This toxicity was attenuated by nordihydroguaiaretic acid but not by indomethacin, indicating that lipoxygenase pathway of AA metabolism is involved in the toxicity. Furthermore, the neurotoxic action of AA was abolished by antioxidants butylated hydroxyanisole or N-acetylcysteine. In contrast, treatment with forskolin or high K+, which have been shown to prevent neuronal death induced by MPP+ or high oxygen conditions, showed no protection against AA toxicity. These results suggest that, although oxygen free radicals generated through lipoxygenase metabolism is responsible for the neurotoxicity, distinct mechanisms from those of other oxidative stress are operative in AA-induced neuronal injury.

Animals↗
PubMed1995

Neurotrophic effects of conditioned media of astrocytes isolated from different brain regions on hippocampal and cortical neurons.

The present study was designed to reveal whether astroglial cells from different brain regions produce diffusible factors that differentially support the survival of neurons and the establishment of neuronal morphology. For this purpose, astrocyte conditioned media (ACM) were prepared by conditioning chemically-defined medium with type I astrocyte culture dissociated from cerebral cortex, hippocampus and hypothalamus. Hippocampal and cortical neurons were cultured in ACM or in non-conditioned medium. ACM derived from three brain regions all supported the survival of hippocampal and cortical neurons better than non-conditioned control medium. Of these, hypothalamic ACM was the most effective in supporting the survival of cortical neurons. The ACM also potentiated the elongation of the longest neurite of hippocampal and cortical neurons. However, there were no significant differences in the promoting effects on neurite elongation among ACM from three brain regions.

Animals↗
PubMed1995

Effects of vitamin B6 and its related compounds on survival of cultured brain neurons.

The effects of pyridoxine and its derived cofacter, pyridoxal phosphate (PLP) on the survival of primary cultured neurons from fetal rat brain were investigated. Pyridoxine and PLP significantly promoted the neuronal survival of various brain regions in high cell density culture (10(5) cells/cm2), but showed no positive effects on hippocampal neurons in low cell density culture (5 x 10(3) cells/cm2). This neurotrophic effect of PLP was remarkably suppressed by picrotoxin and ifenprodil. Aminooxyacetic acid (AOAA), an inhibitor of PLP dependent enzymes, caused significant neuronal loss by itself, and largely counteracted the neurotrophic effect of PLP. Taken together, we presume that vitamin B6 afforded the survival-promoting activities of cultured neurons by virtue of its crucial coenzymatic actions in the biosynthesis of putative neurotransmitters.

Aminooxyacetic Acid↗
PubMed1995

Arachidonic acid as a neurotoxic and neurotrophic substance.

In this article we summarize a wide variety of properties of arachidonic acid (AA) in the mammalian nervous system especially in the brain. AA serves as a biologically-active signaling molecule as well as an important component of membrane lipids. Esterified AA is liberated from the membrane by phospholipase activity which is stimulated by various signals such as neurotransmitter-mediated rise in intracellular Ca2+. AA exerts many biological actions which include modulation of the activities of protein kinases and ion channels, inhibition of neurotransmitter uptake, and enhancement of synaptic transmission. AA serves also as a precursor of a variety of eicosanoids, which are formed by oxidative metabolism of AA. AA cascade is activated under several pathological conditions in the brain such as ischemia and seizures, and may be involved in irreversible tissue damage. On the other hand, AA can show beneficial influences on brain tissues and cells in several situations. In a recent study using cultured brain neurons, we have found that AA shows quite distinct actions at a narrow concentration range, such as induction of cell death, promotion of cell survival and enhancement of neurite extension. The neurotoxic action is mediated by free radicals generated by AA metabolism, whereas the neurotrophic actions are exerted by AA itself. The observed in vitro actions of AA might be related to important roles of AA in brain pathogenesis and neural development.

Animals↗
PubMed1995

The effects of thiamine and oxythiamine on the survival of cultured brain neurons.

The effects of treatment with thiamine (Vitamin B1) alone or together with its antagonist oxythiamine on the survival of brain neurons in primary culture were investigated. Treatment with thiamine significantly promoted the survival of hippocampal neurons in high cell density culture, but had no effects on the neuronal survival in low cell density culture. In addition, the survival-promoting activity exerted by thiamine was remarkably decreased by the co-application of oxythiamine, although oxythiamine used alone revealed neither a trophic nor toxic effect on the neurons of examined brain regions. The neurotrophic function of thiamine may be due to its coenzymatic role in a biochemical reaction and/or its specific function on neurotransmission and nerve conduction.

Animals↗
PubMed1994

Primary culture of postnatal rat suprachiasmatic neurons in serum-free supplemented medium.

We have previously reported that postnatal hypothalamic neurons can be maintained in low density culture using astrocyte conditioned medium. The present study was designed to establish a method for the culture of postnatal hypothalamic neurons in a chemically defined medium. Neurons were dissociated from the suprachiasmatic nucleus (SCN) of the hypothalamus of 21-day-old rats and plated on plastic dishes. First, the effects of several factors which have been known to exert trophic effects on neuronal cells were examined in culture medium containing 10% fetal bovine serum. We have found that platelet-derived growth factor, interleukin-1 beta and vitronectin in combination markedly increased the number of surviving neurons bearing processes. Next we tested such effects in serum-free minimum essential medium. When these factors were added together the SCN neurons could be maintained in culture for up to 3 weeks without medium change. In this supplemented medium, SCN neurons gradually extended processes from 3-5 days after plating, and the cell number with processes reached maximal at days 8-11. The cells were identified as SCN neurons by the immunocytochemical staining for microtubule-associated protein 2 (MAP2) and vasoactive intestinal polypeptide. This culture method may be valuable for investigating the electrophysiological properties and the mechanisms of regeneration of mature central neurons.

Animals↗
PubMed1994

Inhibition by 5-HT7 receptor stimulation of GABAA receptor-activated current in cultured rat suprachiasmatic neurones.

1. Whole-cell voltage-clamp recordings were made from postnatal rat suprachiasmatic (SCN) neurones to investigate possible modulation by 5-hydroxytryptamine (5-HT) of gamma-aminobutyric acid (GABA)-activated current (IGABA). 2. 5-HT reversibly inhibited IGABA in a concentration-dependent manner (10(-10) to 10(-6) M). (+/-)-8-Hydroxy-2-N,N-dipropylaminotetralin (8-OH-DPAT, 10(-10) to 10(-5) M) and 5-carboxamidotryptamine (10(-6) M) also inhibited IGABA, whereas 1-(2,5-dimethyl-4-iodophenyl)-2-aminopropane (DOI, 10(-6) M) had no significant effect. 3. The effect of 8-OH-DPAT (10(-7) M) was blocked by ritanserin (10(-7) M), but not by pindolol (10(-7) M). The effect of 5-HT was also suppressed by ritanserin, but not by pindolol, ketanserin (10(-7) M) or ICS 205-930 (10(-6) M). 4. 8-Bromo-cAMP (10(-3) M) or forskolin (5 x 10(-5) M) suppressed IGABA. The effects of forskolin and 5-HT were not additive. Furthermore, the effect of 5-HT (10(-7) M) was significantly reduced by N-[2-(methylamino)ethyl]-5-isoquinoline sulphonamide (H-8, 10(-6) M). 5. It is concluded that 5-HT inhibits IGABA in the SCN neurones, which involves the activation of 5-HT7 receptors and cAMP-coupled systems.

8-Hydroxy-2-(di-n-propylamino)tetralin↗