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.

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.

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.

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+.

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.

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.

Construction of a plasmid for high level expression of Escherichia coli phosphoenolpyruvate carboxylase.

The minimum size DNA fragment (3011 bp) containing the entire phosphoenolpyruvate carboxylase [EC 4.1.1.

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.

Arachidonic acid: toxic and trophic effects on cultured hippocampal neurons.

Arachidonic acid (20:4) is a component of membrane lipids that has been implicated as a messenger both in physiological and pathophysiological processes, including ischemic injury and synaptic plasticity. In order to clarify direct trophic or toxic effects of arachidonic acid on central neurons, primary cultures of rat hippocampal neurons were exposed to arachidonic acid under chemically-defined conditions. Arachidonic acid present in the culture medium at concentrations over 5 x 10(-6) M showed profound toxicity, whereas at lower concentrations (10(-6) M) it significantly supported the survival of hippocampal neurons.

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.

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.

3,5,3'-L-triiodothyronine promotes survival and axon elongation of embryonic rat septal neurons.

The effect of 3,5,3'-L-triiodothyronine (T3) on survival and morphology of primary cultured neurons of the fetal rat brain was studied. In defined conditions of serum-free culture media we found the death preventing effect of T3 in all tested neuronal populations cultivated at high initial densities of plating (10(5) cells/cm2). While the survival of cerebrocortical neurons was improved very slightly, the number of surviving hippocampal and septal neurons reached 127.

Divergent trophic actions of glioma conditioned media on cultured rat hippocampal neurons.

Neuron-glia interaction is considered to be important for the establishment and maintenance of neuronal shape and polarity during development. Glial cells release a number of trophic factors, many of which have not been fully characterized. In the present study, the trophic influences of conditioned media (CMs) of four glioma cell lines (T98G, Hs683, AC, C6) were tested on cultured hippocampal neurons dissociated from fetal rat brain.

Pharmacological characteristics of GABAA responses in postnatal suprachiasmatic neurons in culture.

The suprachiasmatic nucleus (SCN) is considered to be an endogenous circadian pacemaker. Previous studies have suggested functional roles of gamma-aminobutyric acid (GABA) in the control of circadian rhythms. In this study, the responses to applied GABA in cultured SCN neurons dissociated from postnatal rat hypothalamus were investigated using whole-cell voltage-clamp techniques.

Synergism of tocopherol and ascorbate on the survival of cultured brain neurones.

The effects of antioxidants tocopherols and ascorbic acid were tested on the survival of hippocampal and striatal neurones in dissociated culture. Alpha- and gamma-tocopherol increased the number of surviving neurones in a concentration-dependent manner. Significant effect was observed at concentrations of 10(-8)-10(-6) M.

The involvement of muscarinic, beta-adrenergic and metabotropic glutamate receptors in long-term potentiation in the fimbria-CA3 pathway of the hippocampus.

Possible modulatory actions of endogenous neurotransmitters on long-term potentiation (LTP) were investigated in the fimbria-CA3 pathway of rat hippocampal slices. Bath application of atropine (10 microM), but neither timolol (10 microM) nor D,L-2-amino-3-phosphonopropionate (AP3, 100 microM), significantly attenuated LTP induced by 20 pulses of 50 Hz stimulation. When stronger stimulation (3 trains of 100 Hz, 100 pulses) was used for the induction of LTP, timolol significantly attenuated LTP, but atropine and AP3 did not.

Possible physiological roles of aspartase, NAD- and NADP-requiring glutamate dehydrogenases of Pseudomonas fluorescens.

The levels of aspartase, NADP- and NAD-requiring glutamate dehydrogenases (GDHs) in Pseudomonas fluorescens grown under various nutritional conditions were determined. NADP-GDH showed the highest value on glucose-ammonium sulfate medium and markedly lower values on amino-acid and casamino-acids media, while the reverse was found for the NAD-GDH, as in the case of other microorganisms with two GDHs. Aspartase did not show a marked variation between the media examined.

Involvement of postsynaptic G proteins in hippocampal long-term potentiation.

The possible involvement of postsynaptic guanosine 5-triphosphate (GTP)-binding proteins (G proteins) in long-term potentiation (LTP) was studied in rat hippocampal slices, using whole-cell recording techniques. The inclusion of guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) or guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) in the recording pipette significantly reduced or abolished the baclofen-induced hyperpolarization of pyramidal neurons, which indicates uncoupling of the signal transduction from G protein-coupled receptors by these compounds. Both GDP beta S and GTP gamma S significantly attenuated the magnitude of LTP in the fimbria-CA3 synapses, but not in the mossy fiber-CA3 synapses.

YM-14673, a new thyrotropin-releasing hormone analog, augments long-term potentiation in the mossy fiber-CA3 system of guinea pig hippocampal slices.

Effects of a new thyrotropin-releasing hormone (TRH) analog, N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]L-histidyl-L-prolinamide dihydrate (YM-14673), which improves experimentally induced memory dysfunction, on long-term potentiation (LTP) in the mossy fiber-CA3 system, were investigated using guinea pig hippocampal slices. At concentrations of 10(-7) M and 10(-6) M, YM-14673 significantly augmented LTP in a concentration dependent manner. The magnitude of effect of 10(-6) M YM-14673 was similar to that of 10(-6) M TRH.

Separate mechanisms of long-term potentiation in two input systems to CA3 pyramidal neurons of rat hippocampal slices as revealed by the whole-cell patch-clamp technique.

Excitatory synaptic transmission from two input systems to hippocampal CA3 pyramidal neurons was investigated by the whole-cell patch-clamp technique for thin slice preparation, with special reference to long-term potentiation (LTP) in these systems. Excitatory postsynaptic currents (EPSCs) evoked by fimbrial stimulation consisted of two components; one was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the other was persistent at depolarized membrane potentials and blocked by D-2-amino-5-phosphonovalerate (D-AP5). The contribution of the D-AP5-sensitive component to EPSCs evoked by stimulation of mossy fibers was much less than that to fimbrial EPSCs.

Effects of thyrotropin-releasing hormone and a related analog, CNK-602A, on long-term potentiation in the mossy fiber-CA3 pathway of guinea pig hippocampal slices.

The effects of thyrotropin-releasing hormone (TRH) and a related analog, CNK-602A, that induces the release of catecholamines, on long-term potentiation (LTP) of the population spike in mossy fiber-CA3 pathways were investigated in guinea pig hippocampal slices. TRH augmented LTP of the population spike at concentrations of 10(-6)-10(-5) M. CNK-602A also augmented LTP at concentrations of 10(-6)-10(-5) M in a dose-dependent manner.

Smoking and health: a review prepared by the Smoking and Health Subcommittee of the Tobacco Industries Council, a council formed by the Minister of Finance of Japan.

Any definition of health is inevitably broad and contains various elements that may differ from one individual to another. Recent studies on the effects of smoking on physical and mental health have progressed remarkably and have great value in the fields of epidemiology, pathology, clinical medicine, and psychiatry. This report concludes that while smoking may have beneficial psychological effects on smokers, it may pose a risk to physical health.

Age-related deterioration of long-term potentiation in the CA3 and CA1 regions of hippocampal slices from the senescence-accelerated mouse.

Long-term potentiation (LTP) is one candidate for the mechanism underlying memory storage. In the present study, we carried out electrophysiological studies on hippocampal slices prepared from the senescence-accelerated mouse (SAM-P/8), a strain which shows accelerated senescence and failure of certain types of learning in behavioral tests. The findings were compared with those noted in the SAM-R/1 substrain without severe symptoms of senescence.