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We investigated modification of the MK-801 effect on motor activity and extracellular amines concentration by 6-hydroxydopamine (6-OHDA)-induced lesion of core nucleus accumbens (cACC) of rats. In vivo microdialysis-HPLC showed that the concentrations (fmol/microl) of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and serotonin were 0.738 +/- 0.135, 155.34 +/- 41.01 and 0.334 +/- 0.024, respectively, in the cACC of intact rats. The DOPAC/DA ratio was 264.24 +/- 94.01. Unilateral lesion of the cACC with 6-OHDA (8 microg/microl) substantially reduced DA (-93%) and DOPAC (-97%) in desipramine (30 mg/kg, i.p.)-pretreated rats (6-OHDA+DMI rats) as compared to the 65% reduction rate of both amines in saline-pretreated rats (6-OHDA+saline rats). Moreover, DOPAC was reduced by 72% in 6-OHDA+DMI rats. MK-801 increased DOPAC (426-467%) and DOPAC/DA ratio (180-230%) in intact rats. On the other hand, MK-801 increased DA by 154% and 505% in 6-OHDA+saline and 6-OHDA+DMI rats, respectively. 6-OHDA reduced the effect of MK-801 on DOPAC and DOPAC/DA ratio. In the behavioral studies, MK-801 (0.01-0.3 mg/kg, i.p.) increased locomotor activity and rearing of intact rats. Bilateral 6-OHDA+DMI lesion of the cACC caused greater reduction in the effect of MK-801 (0.1 mg/kg) than that of the shell nucleus accumbens. These results suggest that increased extracellular DOPAC concentration (but not DA) and DOPAC/DA ratio in the cACC plays an important role in MK-801-hyperactivity.

Basic investigations to apply the rapid quenched Nd-Fe-B die-upset technique to fabricate trapezoid-shaped magnets with high energy product were undertaken. Stress around the magnets with indentations during die-upsetting was evaluated by computer simulation. The dimensions of preform shape for isotropic consolidated magnets before hot deformation were determined from compression tests using an aluminum alloy. Hot deformation to obtain the final trapezoid-shape was divided into two steps. The total reduction in height during compression exceeded approximately 72%, and the finished magnets had no cracks. By this method, trapezoid-shaped die-upset magnets with a high energy product of >320 kJ/m/sup 3/ have been fabricated. >

A duality is introduced between a pair of polynomial twisted de Rham cohomology groups associated with a generalized Airy function in several variables. Natural bases of the twisted de Rham groups are constructed in terms of Schur polynomials. Then the intersection matrix relative to these bases is calculated explicitly in terms of skew-Schur polynomials.

The classical harmonic functions are characterized in terms of the mean value property with respect to the unit ball. Replacing the ball by a polytope, we are led to the notion of polyhedral harmonic functions, i.e., those continuous functions which satisfy the mean value property with respect to a given polytope. The study of polyhedral harmonic functions involves not only analysis but also algebra, including combinatorics of polytopes and invariant theory for finite reflection groups. We give a brief survey on this subject, focusing on some recent results obtained by the author.

We have been reported that the repeated cerebral ischemia induced more severe disruption of spatial cognition than single ischemia without any other motor disturbance in 8-arm radial maze task in rats. And we have been clarified that it is corresponding with 60% of selective cell injury of the CA1 pyramidal cells in the hippocampus. Recently, characteristics of apoptosis such as internucleosomal DNA fragmentation have been found in excitotoxic neuronal death. In the present study, we investigated how necrosis and apoptosis following repeated ischemia involve to the cell death. Repeated cerebral ischemia (10 min x 2, 1 hr interval) induced significant disruption of spatial cognition not only 24 hrs but also 7 days after reperfusion. The decrease of H.E-positive neurons was found in the hippocampus CA1 area and frontal cortex within 3 days after reperfusion, while an DNA fragmentation and TUNNEL-positive neurons in the same areas were found afterward. Furthermore repeated cerebral ischemia-induced disruption of spatial cognition and apoptosis in the hippocampal CA1 area were inhibited by YM-90 K(15 mg/kg,i.p.), which is a selective AMPA/KA receptor antagonist, but not by MK-801. These results suggested that the apoptotic cell death may be occurred via non-NMDA receptor mechanism in relatively late phase of the reperfusion period and it may relate to the incidence of the disruption of spatial cognition in the rat.

Polyhedral harmonics is a subject which deals with the problem of characterizing the continuous functions satisfying the mean value property with respect to a polytope. The main feature of it is the finite dimensionality of the space of polyhedral harmonic functions. The theory involves not only analysis but also algebra and combinatorics, and has a. rather different flavor from classical harmonic analysis. This paper aims at providing a survey on the subject, focusing on the author’s recent results.

A calretinin enriched cell culture system which comprised approximately 40% of the total neuronal population of the E14 rat embryo was established from the region of the thalamic eminence (TE), and the effects of several neurotrophins on the neurite growth of calretinin-immunoreactive (CR-IR) neurons was investigated. A 4-day treatment of BDNF significantly increased the ratio of CR-IR to microtubule-associated protein 2-immunoreactive neurons at concentrations between 50 and 250 ng/ml. IGF-I at 100 ng/ml and TGF-alpha at 250 ng/ml also increased this ratio. None of the neurotrophins examined increased the number of primary neurites. BDNF did, however, increase the number of secondary neurites. BDNF-treated primary and secondary neurites were also significantly longer than neurites from neurons in control cultures. IGF-I elicited an increase in primary neurite length, but did not affect either number or length of secondary neurites. TGF-alpha had no effect on either number or length of the primary and secondary neurites. These results indicate that the maturation and development of CR-IR neurites is specifically affected by BDNF. It is suggested that BDNF increases the CR concentration above the threshold of detection by immunohistochemistry in cells and stimulates the sprouting of secondary CR-IR neurites.

To address the role of brain gangliosides in synaptic activity, the ceramide analogs, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) and its enantiomer, L-PDMP, were used to inhibit and stimulate ganglioside biosynthesis in cultured cortical neurons. Prolonged treatment with both PDMP isomers exhibited opposite effects on functional synapse formation measured by spontaneous synchronized oscillatory activity of intracellular Ca2+ between the neurons: suppression by D-PDMP and facilitation by L-PDMP. Up-regulation of synaptic activity by L-PDMP could be correlated with the slow but robust stimulation of ganglioside biosynthesis through activating GM3, GD3 and GQ1b synthases. In a similar time course, the activity of p42 mitogen-activated protein kinase was also enhanced by L-PDMP. To evaluate the efficacy of this drug in long-term memory, rats were trained for 2 weeks using an 8-arm radial maze task, and then forebrain ischemia was induced by 4-vessel occlusion. Treatment with L-PDMP starting 24 hours after the transient ischemia ameliorated the deficit of a well-learned spatial memory, demonstrating the potential therapeutic intervention of the ceramide analog for neurodegenerative disorders.

We investigated the disruption of spatial cognition due to transient forebrain ischemia using an 8-arm radial arm maze task in rats. Five or 10 min of ischemia did not affect the task acquisition. When rats established spatial cognition by daily training of the task, 10 min of ischemia significantly decreased the number of correct choices and increased the errors in the task when performed 24 h after reperfusion. These changes, however, returned to the normal level after about 4 days of daily training. Glutamic acid (Glu) and acetylcholine (ACh) release from the dorsal hippocampus (DH) was observed to transiently increase during ischemia. However, neither the content of noradrenaline (NA) nor the release of NA in the DH changed during ischemia. The NA and ACh release from the DH, however, gradually decreased during reperfusion, and the decrease became significant at 24 h after reperfusion. The NA content of the frontal cortex (FC) and the DH increased 7 days after reperfusion. These results suggest that the disruption of spatial cognition induced by 10 min of ischemia may be attributed to a greater degree to the dysfunction of the hippocampal ACh and NA, and cortical NA systems, rather than to the development of neuronal cell death in these areas.

Overexpression of the familial Alzheimer's disease gene Presenilin 2 (PS2) in nerve growth factor-differentiated PC12 cells increased apoptosis induced by trophic factor withdrawal or beta-amyloid. Transfection of antisense PS2 conferred protection against apoptosis induced by trophic withdrawal in nerve growth factor-differentiated or amyloid precursor protein-expressing PC12 cells. The apoptotic cell death induced by PS2 protein was sensitive to pertussis toxin, suggesting that heterotrimeric GTP-binding proteins are involved. A PS2 mutation associated with familial Alzheimer's disease was found to generate a molecule with enhanced basal apoptotic activity. This gain of function might accelerate the process of neurodegeneration that occurs in Alzheimer's disease, leading to the earlier age of onset characteristic of familial Alzheimer's disease.

2-a13 Presynaptic but not postsynaptic silent synapses re expressed with advanced aging of astrocyte in vitro iroyuki Kawano1 , Shutaro Katsurabayashi1, Kaori Kubota1, otaro Takasaki1,2, Kenichi Mishima1,2, Katsunori Iwasaki1,2, ichihiro Fujiwara1 Dept. of Neuropharmacol., Faculty of Pharmaceutical Science, Fukuoka niv., Fukuoka, Japan 2 A.I.G. Institute for Aging & Brain Science, Fukuoka niv., Fukuoka, Japan

The effects of delta 9-tetrahydrocannabinol (delta 9-THC) on the rise in intracellular Ca2+ concentrations ([Ca2+]i) after stimulation with 15 mM or 29 mM K+ in rat whole brain synaptosomes were examined. A fluorescent chelating agent, Rhod-2, was employed to monitor any alterations of K(+)-evoked [Ca2+]i. Pretreatment with 10(-10) M delta 9-THC for 3 min enhanced K(+)-evoked [Ca2+]i significantly, while 10(-9), 10(-8) or 5 x 10(-8) M delta 9-THC significantly inhibited the K(+)-evoked [Ca2+]i. These results suggest that delta 9-THC had a biphasic effect on the K(+)-evoked Ca2+ response in rat brain synaptosomes.

This chapter presents fundamental definitions and theorems on the theory of differential equations which are needed in the course of this book. We do not give proofs for the theorems in Section 1 and 2; the reader may consult any introductory book on differential equations.

The most important non-linear ordinary differential equations are the following six Painleve equations: $$ \begin{array}{*{20}c} {P_I :\frac{{d^2 \lambda }} {{dt^2 }} = 6\lambda ^2 + t,} \\ {P_{II} :\frac{{d^2 \lambda }} {{dt^2 }} = 2\lambda ^3 + t\lambda + \alpha ,} \\ {P_{III} :\frac{{d^2 \lambda }} {{dt^2 }} = \frac{1} {\lambda }\left( {\frac{{d\lambda }} {{dt}}} \right)^2 - \frac{1} {\lambda }\frac{{d\lambda }} {{dt}} + \frac{1} {t}(\alpha \lambda ^2 + \beta ) + \gamma \lambda ^3 + \frac{\sigma } {\lambda },} \\ {P_{IV} :\frac{{d^2 \lambda }} {{dt^2 }} = \frac{1} {{2\lambda }}\left( {\frac{{d\lambda }} {{dt}}} \right)^2 - \frac{3} {2}\lambda ^3 + 4t\lambda ^4 + 2(t^2 - \alpha )\lambda + \frac{\beta } {\lambda },} \\ {P_V :\frac{{d^2 \lambda }} {{dt^2 }} = \left( {\frac{1} {{2\lambda }} + \frac{1} {{\lambda - 1}}} \right)\left( {\frac{{d\lambda }} {{dt}}} \right)^2 - \frac{1} {t}\frac{{d\lambda }} {{dt}} + \frac{{(\lambda - 1)^2 }} {t}(\sigma \lambda + \frac{\beta } {\lambda }) + \gamma \frac{\lambda } {t} + \sigma \frac{{\lambda (\lambda + 1)}} {{\lambda - 1}},} \\ {P_{VI} :\frac{{d^2 \lambda }} {{dt^2 }} = \frac{1} {2}\left( {\frac{1} {\lambda } + \frac{1} {{\lambda - 1}} + \frac{1} {{\lambda - t}}} \right)\left( {\frac{{d\lambda }} {{dt}}} \right)^2 - \left( {\frac{1} {t} + \frac{1} {{t - 1}} + \frac{1} {{\lambda - t}}} \right)\frac{{d\lambda }} {{dt}} + \frac{{\lambda (\lambda - 1)(\lambda - 1)}} {{t^2 (t - 1)^2 }}\left[ {(\sigma - \beta \frac{t} {{\lambda ^2 }} + \gamma \frac{{t - 1}} {{(\lambda - 1)^2 }} + \left( {\frac{1} {2} - \delta } \right)\frac{{t(t - 1)}} {{(\lambda - t)^2 }}} \right],} \\ \end{array} $$ where α, β, γ, δ are complex constants. (Warning: The parameters of P VI are slitely different from those customarily used; -β and ½ - δ have been denoted by β and δ. The reason of our choice will turn out to be clear in the text.) We study, in this chapter, these differential equations first classically (§1) and secondly in the framework of the monodromy preserving deformation. After introducing the concept of monodromy preserving deformation (§2, §3), we derive the Gamier system written in the form of Hamiltonian system, which governs such deformation of a second order Fuchsian equation with n+3 singularities (§4).

Consider a system of nonlinear ordinary differential equations of the form $$ y' = g_i (x,y_1 , \cdots ,y_n )\quad (i = 1, \cdots ,n) $$ (0.0.1) in n unknowns y1, ... y n , where the g i ’s are meromorphic in x, y1,..., y n with poles along x = a. We say that equation (0.0.1) has a singular point of regular type at re = a if every g i has at most a simple pole at x = a, and of irregular type otherwise.

To improve the magnetic properties and hot workability of anisotropic Nd-Fe-Co-B-Ga die upset magnets, the effects of inner lubricants were studied. BN, MoS/sub 2/, and graphite powder were employed as inner lubricants. Additions of small amounts of graphite powder were the most effective lubricant among the three types of inorganic agents. By employing liquid lubricants instead of inorganic solid lubricants, further improvement in magnetic properties and in the ability to flow when hot were achieved. Die upset magnets with 0.3 wt.% oleic acid showed 4 pi Ir=12.6 kG, iH/sub c/=15.7 kOe, and (BH)/sub max/=38.5 MG-Oe. The increase in energy product was 7 MG-Oe compared with unlubricated magnets. X-ray diffraction revealed that the improvement was caused by better crystal alignment along the compression direction during plastic flow. Inner lubricants were found to work effectively as grain growth inhibitors in flake interfaces during hot working. >

It is well known that the sixth Painleve equation $\PVI$ admits a group of Backlund transformations which is isomorphic to the affine Weyl group of type $\mathrm{D}_4^{(1)}$. Although various aspects of this unexpectedly large symmetry have been discussed by many authors, there still remains a basic problem yet to be considered, that is, the problem of characterizing the Backlund transformations in terms of Riemann-Hilbert correspondence. In this direction, we show that the Backlund transformations are just the pull-back of very simple transformations on the moduli of monodromy representations by the Riemann-Hilbert correspondence. This result gives a natural and clear picture of the Backlund transformations. Key words: Backlund transformation, the sixth Painleve equation, Riemann-Hilbert correspondence, isomonodromic deformation, affine Weyl group of type $\mathrm{D}_4^{(1)}$.

Cyclodextrins (CyDs) protected the human erythrocytes from haemolysis induced with chlorpromazine (CPZ) in isotonic solution, depending upon the magnitude of the stability constant of CPZ-CyD complexes (β-> γ-> α-CyD). From the observations of CPZ uptake into erythrocytes and changes in surface activity of CPZ, the protective effects of CyDs in vitro appeared to be due to the decrease in effective haemolytic concentration of CPZ through inclusion complex formation rather than the direct interaction of CyDs with the erythrocyte membrane. The effect of β-CyD on some central nervous system (c.n.s.) actions of CPZ in rats was also investigated to see if there were any advantages in the use of β-CyD complexes given by injection. The results suggest that β-CyD does not alter the time-course or magnitude of the effects of CPZ on the c.n.s.

Changes in brain catecholamine content after lesioning the nucleus accumbens (ACC) and the effects of antidepressants were investigated using HPLC-ECD. ACC lesion reduced dopamine (DA) in the rostral caudate-putamen (r-CP), lateral hypothalamus (LH) and central amygdala (ACE). Imipramine (IMP) and nomifensine (NOM) increased DA in r-CP, caudal (c)-CP and basolateral amygdala. Mianserin (MIAN) and zimelidine (ZIM) increased DA only in c-CP. ACC lesion did not change DOPAC. Only IMP (in c-CP) and NOM (in r-CP and c-CP) increased DOPAC. Noradrenaline (NA) was decreased in c-CP and ACE after ACC lesion. IMP and ZIM displayed no effect on NA, while NOM increased NA in LH and frontal cortex (FC) and MIAN only in FC. These results suggest an important role for DA but not NA in the exhibition of muricide after ACC lesion, and in the antimuricide effect of antidepressants.

To understand the role of the Ga addition which enhances coercivity in Nd/sub 14/Fe/sub 79.25/B/sub 6/Ga/sub 0.75/ die upset magnets, metallurgical investigations using Auger electron spectroscopy (AES) and energy-dispersive x-ray spectroscopy-transmission electron microscopy (EDX-TEM) were done. Ga has a tendency to be condensed in the Nd rich phase (higher than 2 wt%) and Ga content in the matrix is around 0.2 wt%. The Ga solution in these phases seems to strengthen the pinning force defined at the interface of the matrix and the Nd rich phase. To improve thermal stability further, the Co substitution for Fe in Nd/sub 14/Fe/sub 79.25-{mu}/Co/sub {mu}/B/sub 6/Ga/sub 0.75/ ({mu} = 0 to 20) magnets was investigated. The Co substitution up to {mu} = 20 does not decrease coercivity, while for sintered magnets the Co substitution decreases coercivity very markedly. The irreversible losses for {mu} = 0 and 7.5 after exposure at 180{sup 0}C are over 10% and under 5%, respectively. Using pulverized Nd/sub 14/Fe/sub 71.75/Co/sub 7.5/B/sub 6/Ga/sub 0.75/ die-upset magnets, anisotropic bonded magnets (compression molded) with 15 MGOe of (BH)/sub max/ and 19 kOe of /sub i/H/sub c/ were obtained. The irreversible loss is under 5% after exposure up to 140{sup 0}C. The results ofmore » these studies are detailed in this paper.« less

In this paper we calculate the Riemann function of Darboux’s Harmonic equation (H). The Riemann function of (H) admits an action of a certain finite group, which permits us to reduce (H) to the system of Appell’s $F_4 $. Then, by using Takano’s integral representation for $F_4 $, we solve a connection problem to find a representation of R in terms of the Appell’s hypergeometric function. We also discuss the symmetry algebras for classical and typical hyperbolic partial differential equations.

The behavioral effects of paroxetine were investigated in mice and rats in comparison with imipramine and amitriptyline. 1) Locomotor activities were decreased by imipramine and amitriptyline but not by paroxetine in both animal species. 2) Paroxetine antagonized methamphetamine-induced hyperactivity in mice as did imipramine and amitriptyline. 3) Paroxetine showed a more potent antimuricidal effect in raphe-lesioned rats than imipramine and amitriptyline, and it also inhibited muricide in olfactory bulbectomized rats. 4) The immobility of rats in the forced swimming test was markedly decreased by imipramine and amitriptyline, but only slightly by paroxetine. 5) Like imipramine and amitriptyline, paroxetine potentiated the methamphetamine- or L-DOPA-induced stereotyped sniffing, and it inhibited oxotremorine-induced tremor. 6) Paroxetine antagonized reserpine-induced hypothermia, tetrabenazine-induced ptosis, and enhanced ether-induced anesthesia, all less potently than imipramine and amitriptyline. 7) The analgesic action of paroxetine was stronger than that of imipramine and amitriptyline. 8) Paroxetine did not antagonize maximal electroshock- or pentetrazol-induced convulsions and haloperidol- or THC-induced catalepsy in rats. In addition, paroxetine neither exerted muscle relaxation nor affected the shuttle-box type conditioned avoidance in rats. From these results, the behavioral effects of paroxetine, as compared with imipramine and amitriptyline, were characterized by its potent antimuricidal action in raphe-lesioned rats and its weak effect in the forced swimming test and by its less potent muscle relaxant, anticonvulsant, anticataleptic and anesthesia-potentiating actions.