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Abstract: This study was a numerical and experimental investigation of low-temperature auto-ignitions behind reflected shock waves in which a shock tube was employed as the experimental system. We used a high-speed video camera and the Schlieren method to visualize the ignition phenomena. Experiments were performed over a temperature range from 549±10 to 1349±11K and a pressure range from 56±2 to 203±13kPa, and a non-diluted stoichiometric acetylene–oxygen mixture was chosen as the combustible gas. We introduced a numerical simulation to help us understand the disturbed temperature distribution behind bifurcated shock waves due to interference between reflected shock waves and the boundary layer developed behind incident shock waves. Additionally, we experimentally observed and evaluated quantitatively a tendency for ignition positions to be located farther from the reflecting wall as the temperature decreased behind reflected shock waves. To focus our attention on the ignition positions, we classified the ignition types behind reflected shock waves as near-wall ignition and far-wall ignition by 4.7mm distance from reflecting wall. The criterion for these ignition types was estimated to be . As a main object in this manuscript, we proposed an ignition model in which local ignition is induced at some distance from reflecting wall based on the numerical simulation and results; the local ignitions at a point distant from the reflecting wall are induced by the temperature rise, with the distance from the reflecting wall, immediately behind concave reflected shock waves due to developing of bifurcated shock waves. We confirmed that there is no discrepancy between the proposed model and experimental results. [Copyright &y& Elsevier]

Abstract: Spherical projectiles were launched into detonable mixtures over a wide range of projectile velocities from near to about 1.8 times the Chapman–Jouguet (C–J) velocity. Oblique detonation waves (ODWs) and shock-induced combustions (SICs) stabilized around the projectiles were visualized with high time and high spatial resolutions using the Schlieren technique and a high-speed camera with a 1-μs frame speed. Unsteady wave structures called Straw Hat type structures consisting of a SIC region followed by a C–J ODW were observed near stabilizing criticalities of a C–J ODW, and they were divided into two propagation types, depending on whether the C–J ODW could be stabilized . In the present study, we suggested wave structures of the Straw Hat types based on our examination of dozens of continuous images. Triple points were observed at the intersection of a bow shock, a C–J ODW and a transverse detonation or shock wave when projectile velocities were slightly higher than C–J velocities. Onsets of local explosions in the SIC region for stabilizing the ODW in the Straw Hat type structures have been reported . We observed this stabilizing mechanism by visualizing onsets of periodical local explosions and their transition to spherical detonation waves when the projectile velocity was much higher than the C–J velocity. We also determined stabilizing criticalities using a stoichiometric acetylene-oxygen mixture diluted with argon or krypton in 50% or 75% volumetric fractions, respectively. We found that the stabilizing criticalities did not depend only on the ratio of the projectile diameter and the cell size of the mixture. [Copyright &y& Elsevier]

Gas dynamics in a simplified pulse detonation engine (PDE) was theoretically analyzed. A PDE was simplified as a straight tube with a fixed cross section. One end of the tube was closed, namely, this end was the thrust wall, and the other end was open. A detonation wave was initiated at the closed end and simultaneously started to propagate toward the open end. When the detonation wave broke out from the open end, a rarefaction wave started to propagate from the open end toward the closed end. This rarefaction wave was reflected by the closed end. By considering this rarefaction wave to be self-similar in the analysis of the interference between this rarefaction wave and its reflection from the closed end, we analytically formulated the decay portion of the pressure history at the closed end (thrust wall) without any empirical parameters. By integrating the obtained pressure history at the thrust wall with respect to time, important performance parameters of a PDE were also formulated. The obtained formulas were compared with numerical and experimental results and agreed with them very well. [ABSTRACT FROM AUTHOR]

Presents a study which examined the generation of a steady-state detonation around a hypersonic projectile in stoichiometric hydrogen-oxygen premixed gases. Elements of the experimental equipment used in the study; History of shock waves around supersonic projectile; Conclusions.

To analyze non-ideal phenomena, such as burned gas backflow and non-detonation combustion, which affect the rotating detonation wave Mach number, simultaneous self-luminous visualization, time-averaged static pressure, fluctuating pressure, and thrust measurements with gaseous ethylene and oxygen were performed. Consequently, by doubling the number density of the fuel injectors, the hydrodynamic blockage ratio at the oxidizer inlet increased approximately 1.7-fold under the same oxidizer inlet area conditions. This may be attributed to the increase in the detonation propagation Mach number owing to the enhanced mixing of fuel and oxidizer. The relationship between the parasitic combustion fraction in front of the rotating detonation wave and the Mach number was also investigated by using a distributed heat release model. Consequently, it was suggested that experimental Mach number decreased from approximately 4.1 to 2.8 with increase in a mixture mass flux, and the theoretical detonation wave propagation Mach number was 7.3. • Mach number of rotating detonation wave was experimentally estimated. • Hydrodynamic blockage ratio increased with number density of fuel injectors. • Propagation speed of detonation wave increased with mixture mass flux. • Fluctuating pressure ratio decreased with increase in mixture mass flux. • The Mach number decreased from 4.1 to 2.8 with increase in mixture mass flux. [ABSTRACT FROM AUTHOR]

Liquid propellants are commonly used in rocket engines due to their high energy density. In this study, we focused on the use of liquid ethanol and liquid nitrous oxide as propellants in a cylindrical rotating detonation engine (RDE) for practical applications, and examined the effects of various conditions on the bipropellant RDE performance. We varied the vapor quality of nitrous oxide in a mixture of liquid and gaseous nitrous oxide due to the flash boiling. In addition, we varied the liquid ethanol temperature, the injector stiffness, and momentum angle of the propellant. We then analyzed the effects of these changes on the propagation mode of the RDE under atmospheric pressure conditions. The results showed that a rotating detonation wave was observed under the combination of high vapor quality of nitrous oxide, high injector stiffness, high liquid ethanol temperature, and high momentum angle. The propagation velocity was obtained as 73∼83 % of the Chapman-Jouguet velocity. Long-duration combustion tests were also conducted, and the internal combustion structure was confirmed from the erosion of the carbon-carbon (C/C) composite material. The detonation wave was considered to propagate near the bottom of the RDE with liquid propellants from the erosion heights of the C/C composite. The erosion height was confirmed to be consistent with the fill height calculated using the sound speed of the nitrous oxide. In addition, characteristic exhaust velocity efficiencies of more than 85 % were achieved in all combustion tests. [ABSTRACT FROM AUTHOR]

Abstract: The detonation propagation phenomena in curved channels were experimentally studied in order to determine the stable propagation condition. A stoichiometric ethylene–oxygen mixture gas and five types of rectangular-cross-section curved channels with different inner radii of curvature were employed. The detonation waves propagating through the curved channels were visualized using a high-speed video camera. Multi-frame short-time open-shutter photography (MSOP) was developed in the present study to simultaneously observe the front shock shape of the detonation wave and the trajectories of triple points on the detonation wave. The detonation wave became more stable under the conditions of a higher filling pressure of the mixture gas and/or a larger inner radius of curvature of the curved channel. The critical condition under which the propagation mode of the detonation wave transitioned from unstable to stable was having an inner radius of curvature of the curved channel (r i) equivalent to 21–32 times the normal detonation cell width (λ). In the stable propagation mode, the normal detonation velocity (D n) increased with the distance from the inner wall of the curved channel and approached the velocity of the planar detonation propagating through the straight section of the curved channel (D str). The smallest D n was observed on the inner wall and decreased with decreasing r i/λ. The distribution of D n on the detonation wave in the stable mode was approximately formulated. The approximated D n given by the formula agreed well with the experimental results. The front shock shape of the detonation wave could be reconstructed accurately using the formula. The local curvature of the detonation wave (κ) nondimensionalized by λ decreased with increasing distance from the inner wall. The largest λκ was observed on the inner wall and increased with increasing r i/λ. D n/D str decreased with increasing λκ. This nondimensionalized D n–κ relation was nearly independent of r i/λ. [Copyright &y& Elsevier]

Abstract: In the present study, we experimentally and numerically investigated the influence of heat transfer and friction on the performance of a single-shot detonation tube open at one end. Two kinds of specific impulse measurement were carried out with various tube lengths and levels of surface roughness, one by using a ballistic pendulum arrangement and the other by integrating the pressure history measured at the thrust wall. These measurements revealed the degree to which potential impulse can be exploited by the detonation tube after the impulse losses due to various wall loss mechanisms such as heat transfer and friction. The detonation tube obtained 89%, 70%, and 64% of the theoretical ideal impulse for electropolished tubes at a ratio of tube length to diameter (L/D) of 49, 103, and 151, respectively. The impulse losses due to shear stress on the side wall of the detonation tube were found to have a dominant influence on the performance of the detonation tubes of L/D =103 and 151, but the loss was remarkably small for L/D =49 relative to that of the longer tubes. In addition to the experiments, a simplified one-dimensional gas-dynamic model was developed by considering heat transfer and friction as wall loss mechanisms and validated by the experimental results. This simplified model was found to predict the experimental results very well, especially in the range of L/D 103–151. [Copyright &y& Elsevier]

Regulation of gene expression is purported as a major component in the long-term action of antidepressants. The transcription factor cAMP-response element-binding protein (CREB) is activated by chronic antidepressant treatments, although a number of studies reported different effects on CREB, depending on drug types used and brain areas investigated. Furthermore, lithe is known as to what signaling cascades are responsible for CREB activation, although cAMP-protein kinase A (PICA) cascade was suggested to be a central player. We investigated how different drugs (fluoxetine (FLX), desipramine (DMI), reboxetine (RBX)) affect CREB expression and phosphorylation of Ser133 in the hippocampus and prefrontal/frontal cortex (PFCX). Acute treatments did not induce changes in these mechanisms. Chronic FLX increased nuclear phospho-CREB (pCREB) far more markedly than pronoradrenergic drugs, particularly in PFCX. We investigated the function of the main signaling cascades that were shown to phosphorylate and regulate CREB. PKA did not seem to account for the selective increase of pCREB induced by FLX. All drug treatments markedly increased the enzymatic activity of nuclear Ca2+/calmoduIin (CaM) kinase IV (CaMKIV), a major neuronal CREB kinase, in PFCX. Activation of this kinase was due to increased phosphorylation of the activatory residue Thr196, with no major changes in the expression levels of α- and β-CaM kinase kinase, enzymes that phosphorylate CaMKIV. Again in PFCX, FLX selectively increased the expression level of MAP kinases Erk1/2, without affecting their phosphorylation. Our results show that FLX exerts a more marked effect on CREB phosphorylation and suggest that CaMKIV and MAP kinase cascades are involved in this effect. [ABSTRACT FROM AUTHOR]

To analyze a rotating detonation cycle (RDC) with burned gas backflow, simultaneous self-luminous visualization, pressure, and thrust measurements with gaseous ethylene and oxygen were performed. Three different geometric blockage ratios (bottom-wall-surface area to cross-sectional area of combustor) were set at 89.2 , 70.2 , and 51.7 %. The fuel and oxidizer mass flow rates and equivalence ratio were constant at 20.6 g / s , 41.2 g / s , and 1.7, respectively. During the combustion test, the single detonation wave rotated at 1557, 1459, and 1353 m/s, and the propagation speed increased proportionally for the geometric blockage ratio. The estimated fuel–oxidizer–based specific impulse was in the range of 148 ± 8 s , and the impact of the geometric blockage ratio and propagation speeds on this specific impulse was not confirmed. The hydrodynamic blockage ratio of the oxidizer injector due to the detonation wave was estimated using the oxidizer plenum pressure. It was found that the hydrodynamic blockage ratio linearly decreased with an increase in the geometric blockage ratio. This important trend suggests that the RDC operation is limited in the region of the lower geometric blockage ratio. It is also predicted that a reduction in the hydrodynamic blockage ratio while maintaining the geometric blockage ratio is required for stable RDC operation and achievement of pressure gain combustion. Moreover, the whole RDC structure including the burned gas back flow successfully visualized at the frame rate of 0.5 and 1 µs. The validity of estimated hydrodynamic blockage ratio was demonstrated by comparison with the visualization experiment. It was concluded that the hydrodynamic blockage ratio was primarily determined mainly by the time scale of the burned gas backflow. [ABSTRACT FROM AUTHOR]

• Asymmetrical use of hind limb was assessed in unilateral 6-OHDA-lesioned mice. • A significantly decreased number of the contralateral stepping was observed. • Levodopa reversed the asymmetry of hind limb in a dose dependent manner. • Counting hind limb steps could be utilized for screening PD therapeutics. Unilateral injection of 6-hydroxydopamine (6-OHDA) is commonly used to generate a rodent model of Parkinson's disease (PD). Although motor deficits of the lower extremities represent one of the major clinical symptoms in PD patients, validated tests for assessing motor impairments of the hind limb in 6-OHDA mice are currently unavailable. We here report the video-based assessments of the asymmetric use of hind limbs in 6-OHDA mice. A significantly decreased number of spontaneous hind limb stepping was observed in the contralateral-to-lesioned side, and was dose dependently reversed by levodopa, suggesting that it could be utilized for screening PD therapeutics. [ABSTRACT FROM AUTHOR]

The multiple-ion-probe measurement method is a method to measure a propagating flame using ion probes installed on the wall surface of a combustion chamber. The dynamic behavior of the propagating flame along the wall surface can be regenerated from the dataset of flame signals from individual ion probes. Although this method only captures flames near the wall surface, the flame propagation behavior can be indirectly visualized. Because this method can attain very high temporal resolution, it can provide precise measurements of high-speed phenomena such as knocking in spark-ignition engines and detonation in detonation combustors. This study aimed to investigate the ability of a developed 64-channel multiple-ion-probe measurement system to characterize a propagating flame. To this end, three flames with substantially different propagation velocities were measured using the proposed multiple-ion-probe measurement system. During the experiments, methane–oxygen stoichiometric mixtures diluted with different amounts of nitrogen were used. The flame propagation velocity varied within the range of several m/s for a turbulent flame to 2.4 km/s for detonation by varying the dilution ratio of nitrogen. In the case where a mixture with a nitrogen mole fraction of 0.71 was used, a phenomenon of repeating stagnation and reacceleration of the propagating flame was observed. Furthermore, the phenomenon considered to be flame quenching was also observed near the wall. In the case of no dilution (nitrogen mole fraction = 0.00), multiple-ion probes with an installation interval of 1.5 mm indicated that the velocity fluctuated within the range of −500 m/s to +2000 m/s with respect to the Chapman–Jouguet detonation velocity of 2390 m/s. Experiments involving soot foil recording conducted in parallel confirmed that this velocity fluctuation was derived from the detonation cell structure and that micro-explosions in the detonation front could be captured using the multiple-ion-probe method. [ABSTRACT FROM AUTHOR]

A high operating frequency of a pulse detonation engine is required to increase the thrust-to-engine weight ratio or thrust density. The semi-valveless pulse detonation cycle (PDC) proposed by Matsuoka et al. (2017) can achieve a high operating frequency exceeding several kilohertz. For achieving a higher operating frequency close to the upper limit of gas dynamics, it is necessary to minimize the process in which the buffer layer is applied to avoid self-ignition of the detonable mixture. Experiments were conducted, and a one-dimensional numerical model was developed to investigate the minimum thickness of the buffer layer and the required duration for the stable PDC operation. Ethylene was used as a fuel and pure oxygen as an oxidizer. The total length of two combustors with an inner diameter of 10 mm was 40 and 80 mm. Therefore, the thickness of the buffer layer of approximately 20 mm was suggested for the stable PDC operation. This result indicated that 10% of the duration of one PDC was required to prevent self-ignition (SI). In the failed PDC, the early and late SI were confirmed. Interestingly, high-frequency PDC operation with a short combustor can suppress late SI and results in a higher success rate with the same thickness of the buffer layer. Furthermore, a stable PDC operation of a 1916 Hz with a combustor with a total length of 40 mm was demonstrated. [ABSTRACT FROM AUTHOR]

In this study, the critical conditions of diffracted detonation waves expressed in terms of reflection point distances in Kawasaki and Kasahara (2020) were investigated for a wider range of fuel-oxidizer mixtures. In H 2 /O 2 , C 2 H 2 /O 2 , C 2 H 4 /O 2 , C 2 H 6 /O 2 , C 3 H 6 /O 2 , C 2 H 6 /N 2 O, and C 3 H 6 /N 2 O mixtures, these mixtures are used to measure the reflection point distance through the modification of the initial pressure and equivalence ratio of the mixture at room temperature. Moreover, the critical ideal reflection point distance divided by the channel width, which this dimensionless parameter was identified in the critical condition region of detonation diffraction. The results revealed that this region was in the range of 3.8 ± 0.8 for all investigated mixtures even though the equivalence ratio varied. The parameter l r,i p 0 is the product of the ideal reflection point distance and the initial pressure, which is proportional to the energy (work) per unit area required for re-initiation. The larger the product of the reflection point distance and the initial pressure, the more difficult the mixture is to re-initiate, and the inverse of this parameter represents the ease of re-initiation, which can be considered an index of detonability. Detonability, which is the objective of clarification in this study, was found to have the order C 2 H 2 /O 2 > C 2 H 4 /O 2 > C 3 H 6 /O 2 > C 2 H 6 /O 2 > H 2 /O 2 in the vicinity of the stoichiometric ratio, which is similar to the case using Matsui and Lee's critical initiation energy. [ABSTRACT FROM AUTHOR]

A reflective shuttling detention combustor (RSDC) is a two-dimensional combustor with two reflection walls. Unlike a rotating detonation combustor (RDC), an RSDC can visualize the entire area of the combustor via an optical technique. In addition, the RSDC can reproduce the counter-rotating detonation mode in RDC. In present study, CH* luminescence and schlieren image were observed to investigate the dynamics of the RSDC. The reflective wall distance was set to 45 mm (Type L) and 25 mm (Type S). As the results, the wave speed of 1226 ± 64 m / s in the single wave mode in Type S was 76% of that in Type L. It was found that the detonation propagation speed decreased with a reduction in the reflection wall distance. Superimposing the luminescence images on the schlieren images revealed that the mixture was mainly burned by deflagration behind shock wave. In addition, the experimental mixture fill height was in good agreement with model in which the mixture filling process was temporarily stopped by detonation and refilled at a constant speed. Using the maximum fill height obtained by the model, it was found that the detonation mode was in the region of 3 ± 0.6 of the dimensionless quantity (the reflection wall distance divided by the wave number and maximum value of the mixture fill height). [ABSTRACT FROM AUTHOR]

Abstract: We developed a rotary valve for a pulse detonation engine (PDE), and confirmed its basic characteristics and performance. In a square cross-section combustor, we visualized a multi-shot of a pulse detonation rocket engine (PDRE) cycle at an operation frequency of 160Hz by using a high-speed camera (time resolution: 3.33μs, space resolution: 0.4mm) and a Schlieren method. The propellant filling process and the purge process were confirmed, and each process was modeled. Moreover, we confirmed the processes of detonation wave generation and burned gas blowdown. In addition, we investigated the impact of shortening the passage width of a combustor and negative-time ignition (ignition time is earlier than the end-time of the propellant filling process) on the deflagration-to-detonation transition (DDT) distance and time. The DDT distance did not depend on the passage width of a combustor and decreased under the negative-time ignition condition. With a passage width of 20mm, the DDT distance decreased by 22% under the negative-time ignition condition to a minimum value (76±8mm). The DDT time from spark time reached a minimum value (69±14μs) under the condition of a passage width of 10mm and negative-time ignition. The detonation initiation time and the DDT distance were represented by the time until the flame expanded toward the tube-axis one-dimensionally from ignition (characteristic time). We also carried out thrust measurement using a PDRE system composed of a circular cross-section combustor and the newly developed valve. We obtained a stable time-averaged thrust in a wide range of operation frequency (40–160Hz) and confirmed the increase of specific impulse due to a partial-fill effect. At a maximum operation frequency of 159Hz, we achieved a maximum propellant-based specific impulse of 232s and a maximum time-averaged thrust of 71N. [Copyright &y& Elsevier]

Dopaminergic neurons are selectively vulnerable to oxidative stress and inflammatory attack. The neuronal cell loss in the substantia nigra is associated with a glial response composed markedly of activated microglia and, to a lesser extent, of reactive astrocytes although these glial responses may be the source of neurotrophic factors and can protect against oxidative stress such as reactive oxygen species and reactive nitrogen species. However, the glial response can also mediate a variety of deleterious events related to the production of pro-inflammatory, pro-oxidant reactive species, prostaglandins, cytokines, and so on. In this review, we discuss the possible protective and deleterious effects of glial cells in the neurodegenerative diseases and examine how these factors may contribute to the pathogenesis of Parkinson's disease. This review suggests that further investigation concerning glial reaction in Parkinson's disease may lead to disease-modifying therapeutic approaches and may contribute to the pathogenesis of this disease. [ABSTRACT FROM AUTHOR]

We evaluated mainly the iNOS (inducible nitric oxide synthase) and nNOS (neuronal NOS) expression in the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in young adult (8-week-old) and aged (60-week-old) mice. The present study demonstrates that the expression of nNOS was more pronounced than that of iNOS expression in the dentate gyrus of aged mice. Our study also suggests that aged mice exhibited a significant loss of motor activity as compared with young adult animals. Furthermore, our results provide that no significant change in the number of Neu N (Neuronal nuclei)-immunopositive neurons and GFAP (glial fibrillary acidic protein)-immunopositive astrocytes was observed in the dentate gyrus between young adult and aged mice. In contrast, a significant change in the number of Iba 1(ionized calcium-binding adaptor molecule 1)-immunopositive microglia in aged mice was observed in the dentate gyrus as compared to young adult animals. These results provide the novel evidence showing that the expression of nNOS may be crucial for the role of neurogenesis of the SGZ of the dentate gyrus in aged mice. Furthermore, our present findings demonstrate that the inhibition of nNOS expression in the SGZ of the dentate gyrus during aging processes may offer novel therapeutic strategies for anti-aging in humans. [ABSTRACT FROM AUTHOR]

Focal brain lesions such as transient focal cerebral ischemia can lead to neuronal damage in remote areas, including the ipsilateral substantia nigra and hippocampus, as well as in the ischemic core. In this study, we investigated acute changes in the ipsilateral hippocampus from 1 up to 7 days after 90 min of transient focal cerebral ischemia in rats, using anti-NeuN (neuronal nuclei), anti-Cu/Zn-superoxide dismutase (Cu/Zn-SOD), anti-Mn-SOD, anti-neuronal nitric oxide synthase (nNOS), anti-inducible NOS (iNOS), anti-glial fibrillary acidic protein (GFAP), anti-ionized calcium-binding adaptor molecule 1(Iba 1) and anti-2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) antibodies. In our western blot and histochemical analyses, present results show that transient focal cerebral ischemia in rats can cause a severe and acute damage of neurons and oligodendrocytes in the ipsilateral hippocampal CA1 sector. The present findings also demonstrate that the expression of iNOS produced by Iba 1-immunopositive microglia precedes the damage of neurons and oligodendrocytes in the ipsilateral hippocampal CA1 sector after transient focal cerebral ischemia. In contrast, our results suggest that increased reactive oxygen species (ROS) production during reperfusion cannot lead to damage of neurons and oligodendrocytes in the ipsilateral hippocampal CA1 sector after transient focal cerebral ischemia, because of an insufficient expression of Cu/Zn-SOD and Mn-SOD. Our double-labeled immunohistochemical study demonstrates that the overexpression of iNOS produced by Iba 1-immunopositive microglia may play a pivotal role in the damage of neurons and oligodendrocytes in the ipsilateral hippocampal CA1 sector at an acute stage after transient focal cerebral ischemia. [ABSTRACT FROM AUTHOR]

We investigated the therapeutic effect of zonisamide against 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice, using Western blot analysis, immunohistochemistry and behavioral test. Our Western blot analysis and immunohistochemical study showed that the post-treatment with zonisamide prevented significantly dopaminergic cell damage, the depletion of tyrosine-hydroxylase (TH) protein levels and the proliferation of microglia in the striatum and/or substantia nigra 8 days after MPTP treatment. Furthermore, our behavioral study showed that the post-treatment with zonisamide attenuated significantly the motor deficits 7 days after MPTP treatment. These results show that zonisamide has the therapeutic effect in the MPTP model of Parkinson's disease (PD) in mice. Our study also demonstrates the neuroprotective effect of zonisamide against dopaminergic cell damage after MPTP treatment in mice. Thus our present findings suggest that therapeutic strategies targeted to the activation of TH protein and/or the inhibition of microglial activation with zonisamide may offer a great potential for restoring the functional capacity of the surviving dopaminergic neurons in individuals affected with PD. [ABSTRACT FROM AUTHOR]

We investigated postnatal alterations of neurons, interneurons and glial cells in the mouse substantia nigra using immunohistochemistry. Tyrosine hydroxylase (TH), neuronal nuclei (NeuN), parvalbumin (PV), neuronal nitric oxide synthase (nNOS), glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba 1), CNPase (2′,3′-cyclic nucleotide 3′-phosphodiesterase), brain-derived neurotrophic factor (BDNF) and glial cell-line-derived neurotrophic factor (GDNF) immunoreactivity were measured in 1-, 2-, 4- and 8-week-old mice. In the present study, the maturation of NeuN-immunopositive neurons preceded the production of TH in the substantia nigra during postnatal development in mice. Furthermore, the maturation of nNOS-immunopositive interneurons preceded the maturation of PV-immunopositive interneurons in the substantia nigra during postnatal development. Among astrocytes, microglia and oligodendrocytes, in contrast, the development process of oligodendrocytes is delayed in the substantia nigra. Our double-labeled immunohistochemical study suggests that the neurotrophic factors such as BDNF and GDNF secreted by GFAP-positive astrocytes may play some role in maturation of neurons, interneurons and glial cells of the substantia nigra during postnatal development in mice. Thus, our findings provide valuable information on the development processes of the substantia nigra. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the postnatal alterations of neuronal nuclei (NeuN)-positive neurons, parvalbumin (PV)-positive interneurons, neuronal nitric oxide synthase (nNOS)-positive interneurons, and neurotrophic factors in the mouse striatum and frontal cortex using immunohistochemistry. NeuN, PV, nNOS, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) immunoreactivity were measured in 1-, 2-, 4- and 8-week-old mice. Total number of NeuN-positive neurons was unchanged in the mouse striatum and frontal cortex from 1 up to 8 weeks of age. In contrast, a significant decrease in the number of PV-positive interneurons was observed in the striatum and frontal cortex of 1-, 2- and 4-week-old mice. Furthermore, a significant increase of nNOS-positive interneurons was found in the striatum and frontal cortex of 1- and/or 2-week-old mice. NGF-positive neurons were unchanged in the mouse striatum from 1 up to 8 weeks of age. In the frontal cortex, a significant increase in the number of NGF-positive neurons was observed only in 1-week-old mice. In contrast, a significant increase in the number of NGF-positive glia 1 cells was found in the striatum and frontal cortex of 4-week-old mice. Our double-labeled immunostaining showed that nNOS immunoreactivity was not found in PV-immunopositive interneurons. Furthermore, BDNF immunoreactivity was observed in both nNOS-positive and PV-positive interneurons in the striatum of 1- or 2-week-old mice. These results show that the maturation of nNOS-immunopositive interneurons precedes the maturation of PV-immunopositive interneurons in the striatum and frontal cortex during postnatal development. Furthermore, our results demonstrate that the expression of BDNF may play some role in the maturation of interneurons in the striatum and frontal cortex during postnatal development. Moreover, our findings suggest that the expression of NGF in glia cells may play some role in the maturation of glial cells and PV-positive interneurons in the striatum and frontal cortex during postnatal development. [Copyright &y& Elsevier]

We investigated the therapeutic effect of zonisamide against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice, using Western blot analysis, immunohistochemistry and behavioral test. Our Western blot analysis and immunohistochemical study showed that the post-treatment with zonisamide prevented significantly dopaminergic cell damage, the depletion of tyrosine-hydroxylase (TH) protein levels and the proliferation of microglia in the striatum and/or substantia nigra 8 days after MPTP treatment. Furthermore, our behavioral study showed that the post-treatment with zonisamide attenuated significantly the motor deficits 7 days after MPTP treatment. These results show that zonisamide has the therapeutic effect in the MPTP model of Parkinson’s disease (PD) in mice. Our study also demonstrates the neuroprotective effect of zonisamide against dopaminergic cell damage after MPTP treatment in mice. Thus our present findings suggest that therapeutic strategies targeted to the activation of TH protein and/or the inhibition of microglial activation with zonisamide may offer a great potential for restoring the functional capacity of the surviving dopaminergic neurons in individuals affected with PD. [ABSTRACT FROM AUTHOR]

Calcium-calmodulin dependent protein kinase IV (CaMKIV) is a protein kinase that activates the transcription factor CREB, the cyclic AMP-response element binding protein. CREB is a key transcription factor in synaptic plasticity and memory consolidation. To elucidate the behavioral effects of CaMKIV deficiency, we subjected CaMKIV knockout (CaMKIV KO) mice to a battery of behavioral tests. CaMKIV KO had no significant effects on locomotor activity, motor coordination, social interaction, pain sensitivity, prepulse inhibition, attention, or depression-like behavior. Consistent with previous reports, CaMKIV KO mice exhibited impaired retention in a fear conditioning test 28 days after training. In contrast, however, CaMKIV KO mice did not show any testing performance deficits in passive avoidance, one of the most commonly used fear memory paradigms, 28 days after training, suggesting that remote fear memory is intact. CaMKIV KO mice exhibited intact spatial reference memory learning in the Barnes circular maze, and normal spatial working memory in an eight-arm radial maze. CaMKIV KO mice also showed mildly decreased anxiety-like behavior, suggesting that CaMKIV is involved in regulating emotional behavior. These findings indicate that CaMKIV might not be essential for fear memory or spatial memory, although it is possible that the activities of other neural mechanisms or signaling pathways compensate for the CaMKIV deficiency. [ABSTRACT FROM AUTHOR]

Actin cytoskeletal remodeling is essential for neurite outgrowth. LIM kinase 1 (LIMK1) regulates actin cytoskeletal remodeling by phosphorylating and inactivating cofihin, an actin filament-disassembling factor. In this study, we investigated the role of LIMK1 in calcium signal-induced neurite outgrowth. The calcium ionophore ionomycin induced LIMK1 activation and cofilin phosphorylation in Neuro-2a neuroblastoma cells. Knockdown of LIMK1 or expression of a kinase-dead mutant of LIMK1 suppressed ionomycin-induced cofilin phosphorylation and neurite outgrowth in Neuro-2a cells. lonomycin-induced cofihin phosphorylation and neurite outgrowth were also blocked by KN-93, an inhibitor of Ca2+/calmoduhin-dependent protein kinases (CaMKs), and STO-609, an inhibitor of CaMK kinase. An active form of CaMKIV but not CaMKI enhanced Thr-508 phosphorylation of LIMK1 and increased the kinase activity of LIMK1. Moreover, the active form of CaMKIV induced cofilin phosphorylation and neurite outgrowth, and a dominant negative form of CaMKIV suppressed ionomycin-induced neurite outgrowth. Taken together, our results suggest that LIMK1-mediated cofilin phosphorylation is critical for ionomycin-induced neurite outgrowth and that CaMKIV mediates ionomycin-induced LIMK1 activation. [ABSTRACT FROM AUTHOR]

Here we explored the mechanism of cardioprotective action of a tyrosine phosphatase inhibitor vanadyl sulfate on myocardial infarction and cardiac functional recovery in rats subjected to myocardial ischemia/reperfusion (MI/R) in vivo. Male Sprague-Dawley rats underwent 30 min heart ischemia by left coronary artery occlusion followed by 24-h reperfusion. Rats were randomized to receive either vehicle or vanadyl sulfate (1 and 5 mg/kg) intraperitoneally 0 min and 30 min after the start of reperfusion. Posttreatment with vanadyl sulfate significantly reduced the infarct size and significantly decreased the elevated left ventricular end diastolic pressure, improved left ventricular developed pressure, and left ventricular contractility (± dP/dt) after 72-h reperfusion in a dose-dependent manner. Moreover, treatment with vanadyl sulfate also significantly inhibited the apoptosis-related Caspase-3 and Caspase-9 processing, thereby elicited the antiapoptotic effect. The cardioprotective effect of vanadyl sulfate was closely associated with restoration of reduced protein kinase B (Akt) activity following MI/R injury. The recovered Akt activity correlated with increased phosphorylation of forkhead transcription factors, FKHR and FKHRL-1, thereby inhibiting apoptotic signaling. Furthermore, treatment with vanadyl sulfate significantly increased FLICE-inhibitory protein (FLIP) expression, and decreased expression of Fas ligand and Bim in cardiomyocytes. Taken together, rescue of cardiomyocytes by posttreatment with vanadyl sulfate from MI/R injury was mediated by increased FLIP expression and decreased Fas ligand and Bim expression via activation of Akt. These results demonstrate that treatment with vanadyl sulfate exerts significant cardioprotective effects along with cardiac functional recovery. [ABSTRACT FROM AUTHOR]

Abstract: Cardiac hypertrophy impairs Ca2+ handling in the sarcoplasmic reticulum, thereby impairing cardiac contraction. To identify the mechanisms underlying impaired Ca2+ release from the sarcoplasmic reticulum in hypertrophic cardiomyocytes, we assessed Ca2+-dependent signaling and the phosphorylation of phospholamban, which regulates Ca2+ uptake during myocardial relaxation and is in turn regulated by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and calcineurin. In cultured rat cardiomyocytes, treatment with endothelin-1, angiotensin II, and phenylephrine-induced hypertrophy and increased CaMKII autophosphorylation and calcineurin expression. The calcineurin level reached its maximum at 72h and remained elevated for at least 96h after endothelin-1 or angiotensin II treatment. By contrast, CaMKII autophosphorylation, phospholamban phosphorylation, and caffeine-induced Ca2+ mobilization all peaked 48h after these treatments. By 96h after treatment, CaMKII autophosphorylation and phospholamban phosphorylation had returned to baseline, and caffeine-induced Ca2+ mobilization was impaired relative to baseline. A similar biphasic change was observed in dystrophin levels in endothelin-1-induced hypertrophic cardiomyocytes, and treatment with the novel CaM antagonists DY-9760e and DY-9836 significantly inhibited the hypertrophy-induced dystrophin breakdown. Taken together, the abnormal Ca2+ regulation in cardiomyocytes following hypertrophy is in part mediated by an imbalance in calcineurin and CaMKII activities, which leads to abnormal phospholamban activity. [Copyright &y& Elsevier]

Abstract: VO(OPT), bis(1-oxy-2-pyridinethiolato)oxovanadium(IV), has been shown to increase tyrosine phosphorylation of proteins and promote the insulin receptor signaling, thereby elicit anti-diabetic action. We here investigated the cytoprotective action of VO(OPT) on myocardial infarction and cardiac functional recovery in rats subjected to myocardial ischemia/reperfusion and defined mechanisms underlying its cytoprotective action. Rats underwent 30 min myocardial ischemia by left anterior descending coronary artery occlusion followed by 24 h reperfusion. Post-ischemic treatment with VO(OPT) significantly reduced infarct size and improved cardiac function (left ventricular developed pressure and ±dP/dt) after 72 h reperfusion and in a dose-dependent manner. Moreover, VO(OPT) treatment also dose-dependently significantly inhibited caspases-3, -9 and -7 processing, thereby elicited the anti-apoptotic effect. The cytoprotective effect of VO(OPT) was closely associated with restoration of Akt activity. The recovered Akt activity correlated with increased phosphorylation of Bad and forkhead transcription proteins, thereby inhibiting apoptotic signaling. Furthermore, treatment with VO(OPT) significantly increased FLIP expression, and decreased expression of Fas ligand and Bim in cardiomyocytes. Taken together, cardiomyocytes rescue following post-treatment with VO(OPT) from ischemia/reperfusion injury was mediated by increased FLIP expression and decreased Fas ligand and Bim expression via activation of Akt. These results demonstrate that treatment with VO(OPT) exerts significant cytoprotective effects along with improvement of cardiac functional recovery. [Copyright &y& Elsevier]

Abstract: Lithium used in bipolar mood disorder therapy protects neurons from brain ischemic cell death. Here, we documented that lithium administration under microsphere-embolism (ME)-induced brain ischemia restored decreased protein kinase B (Akt) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) activities 24 h after ischemia in rat brain. Akt activation was associated with increased phosphorylation of its potential targets forkhead transcription factor (FKHR) and glycogen synthase kinase-3β (GSK-3β). In parallel with decreased CaMKII autophosphorylation, we also found marked dephosphorylation of tau proteins 24–72 h after ME. Increased protein phosphatase 2A (PP2A) activity was found 24 h after ME. Inhibition of increased PP2A activity by lithium treatment apparently mediated restored tau phosphorylation. Taken together, activation of Akt and CaMKII by lithium was associated with neuroprotective activity in ME-induced neuronal injury. [Copyright &y& Elsevier]

DY-9760e (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1 H-indazole dihydrochloride-3.5 hydrate) inhibits Ca2+/CaM-dependent nitric oxide synthase (NOS), thereby inhibiting nitric oxide (NO) production. In cardiomyocytes from ischemic rat heart NO and superoxide levels are increased causing protein tyrosine nitration. In hearts subjected to ischemia/reperfusion DY-9760e totally abolishes protein tyrosine nitration. Notably, DY-9760e also inhibits calpain and cas-pase-3 activation that occurs prior to apoptosis in cardiomyocytes. In ischemic hearts fodrin is the substrate for calpain. DY-9760e inhibits fodrin breakdown in the peri-infarct area rather than in the infarct core. In the ischemic rat brain DY-9760e inhibits caspase-3-induced proteolysis of calpastatin, an endogenous calpain inhibitor, suggesting that crosstalk between calpain and caspase-3 is mediated by calpastatin breakdown. Thus, DY-9760e rescues neurons and cardiomyocytes from ischemic injury by inhibiting crosstalk between calpain and caspase-3 as well as protein tyrosine nitration. [ABSTRACT FROM AUTHOR]

Multifunctional Ca2+/calmodulin-dependent protein kinases (CaMKs) including CaMKI, II and IV, are thought to regulate a variety of neuronal functions. Unlike CaMKII, which is regulated by autophosphorylation, CaMKI as well as CaMKIV are activated by CaMKK. In this study, we examined the cellular and subcellular localization of CaMKIδ, a recently identified fourth isoform of CaMKI, in the mature brain. In situ hybridization analysis demonstrated wide expression of CaMKIδ mRNA in the adult mouse brain with prominent expression in the hippocampal pyramidal cells. FLAG-tagged CaMKIδ was localized at the cytoplasm and neurites without nuclear immunoreactivity in approximately 80% of the transfected primary hippocampal neurons. The stimulation with either KCl depolarization or glutamate triggered the nuclear localization of FLAG-tagged CaMKIδ by two-fold with a peak at 1 min. In contrast, the catalytically inactive mutants of CaMKIδ remained cytoplasmic without nuclear translocation during KCl depolarization, indicating the requirement of its activation for the nuclear translocation. Furthermore, we showed that immunoprecipitated CaMKIδ could phosphorylate cAMP response element binding protein (CREB)α in vitro and that the over-expression of CaMKIδ enhanced GAL4-CREB-luciferase activity in PC12 cells stimulated by KCl depolarization. Our present study provides the first evidence for the possible involvement of CaMKIδ in nuclear functions through its nuclear translocation in response to stimuli that trigger intracellular Ca2+ influx. [ABSTRACT FROM AUTHOR]

Nobiletin is a nonpeptide compound with a low molecular weight from a citrus fruit and has the activity to rescue bulbectomy-induced memory impairment. Here we describe that nobiletin itself induces neurite outgrowth in PC12D cells, a rat pheochromocytoma cell line, like NGF, and the molecular mechanism of its neurotrophic action. As cultured in the presence of nobiletin or NGF for 48 h and then assayed using a scanning electron microscope, PC12D cells treated with nobiletin showed morphology with flatter and larger cell bodies than the cells cultured with NGF. Nobiletin-induced neurite outgrowth was inhibited by PD98059 and U0126 but not K252a. Consistently, nobiletin caused a concentration-dependent enhancement of Erk/MAP kinase phosphorylation and a sustained increment of phosphorylation of MEK and Erk/MAP kinase, resulting in a stimulation of CREB phosphorylation and CRE-mediated transcription. This compound also increased intracellular cAMP and CRE-mediated transcription in the presence of forskolin and enhanced PKA activity to stimulate phosphorylation of multiple PKA substrates in PC12D cells. Furthermore, nobiletin preferentially inhibited Ca2+/CaM-dependent phosphodiesterase in vitro. This compound failed to stimulate phosphorylation of Erk5, which is known to be induced by NGF/TrkA signaling. These results suggest that nobiletin induces neurite outgrowth by activating a cAMP/ PKA/MEK/Erk/MAP kinase-dependent but not TrkA-dependent signaling pathway coupling with CRE-mediated gene transcription and may thus become a novel type of biochemical probe for elucidation of the molecular mechanism of neuronal differentiation. [ABSTRACT FROM AUTHOR]

We have demonstrated an organic thin-film-transistor (OTFT)-driven active-matrix twisted-nematic liquid crystal display (AM-TN-LCD) on a glass substrate, with a resolution of 160 × 120 pixels, 79 ppi. Substrate temperature was kept below the plastic-compatible temperature of 180 °C throughout the fabrication process. In order to realize an OTFT-driven display with fine resolution, we employed short-channel bottom-contact (BC) pentacene OTFTs. It has been known that their drivability is limited by contact resistance at source/drain (S/D). We found that the S/D contact resistance was markedly reduced when the thickness of the nonohmic Ti adhesion layer for ohmic Au S/D electrodes was reduced less than ∼3 nm. We elucidate that this 3 nm corresponds to the thickness of the accumulating layer in a pentacene channel. When we use a self-assembled monolayer of mercapto-silane-coupling agent as the adhesion layer, the contact resistance becomes negligibly small and BC OTFTs scalable below 10 pm were obtained. In addition to this OTFT-cell technology, we developed a low-damage pentacene patterning technique for integration of OTFTs and introduced low-temperature panel assembly process to suppress thermal-stress degradation of pentacene OTFTs, which are the key technologies to achieve OTFT-driven AM-TN-LCD. [ABSTRACT FROM AUTHOR]

Dysregulation of calcium homeostasis is among the major cellular alterations in Alzheimer’s disease (AD). We studied Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), one of the major effectors regulating neuronal responses to changes in calcium fluxes, in cultured skin fibroblasts from subjects with sporadic AD. We found, by using PCR and Western analysis, that human fibroblasts express the δ-isoform of this kinase, and that CaM kinase II is the major Ca2+/calmodulin-dependent kinase in these cells. Protein expression level of the kinase was not significantly different in AD fibroblasts. However, the total activity of the kinase (stimulated by Ca2+/calmodulin) was significantly reduced in AD cell lines, whereas Ca2+-independent activity was significantly enhanced. The percent autonomy of the kinase (%Ca2+-independent/Ca2+-dependent activity) in AD cell lines was 62.8%, three-fold the corresponding percentage in control fibroblasts. The abnormal calcium-independent activity was not due to enhanced basal autophosphorylation of Thr287. The observed abnormalities, if present in brain tissue, may be implicated either in dysfunction of neuroplasticity and cognitive functions or in dysregulation of cell cycle. [Copyright &y& Elsevier]

A circadian clock located in the suprachiasmatic nucleus (SCN) regulates the period of physiological and behavioural rhythms to approximately 24 h. Lithium can lengthen the period of circadian rhythms in most organisms although little is known about the underlying mechanism. In the present study, we examined Drosophila shaggy ortholog glycogen synthase kinase-3 (GSK-3) protein expression in the SCN after lithium treatment. When locomotor activity was assessed, we found an association between the effect of lithium and the period of circadian oscillation as well as the level of GSK-3 protein expression. The decreased expression of GSK-3 and increased expression of phosphorylated GSK-3 (pGSK-3) resulted in an antiphasic circadian rhythm between the two in the SCN of lithium-treated mice housed under both light-dark and constant dark conditions. The enzyme activity of GSK-3 in the SCN was low when the level of pGSK-3 protein was high, as examined by immunoblotting analysis. Thus, GSK-3 enzyme activity has a correlation with the expression of GSK-3 protein in the SCN. Although both GSK-3 and pGSK-3 proteins are also expressed in the arcuate nucleus, lithium did not affect their expression. Based on the association that we found between lengthened circadian period and GSK-3 protein and GSK-3 activity in the SCN, we suggest that GSK-3 plays a role in regulating the period of the mammalian circadian pacemaker. [ABSTRACT FROM AUTHOR]

We have found that spin coating a solution of 6,13-bis(triisopropyl-silylethynyl)-pentacene (TIPS-pentacene) blended with poly(α-methylstyrene) (PαMS) induces vertical nanophase separation, which results in a trilayer film: a TIPS-pentacene layer, a mixed layer of TIPS-pentacene/PαMS, and a TIPS-pentacene layer. Organic thin-film transistors (TFTs) made from this TIPS-pentacene/PαMS solution have remarkably improved uniformity and thermal stability without degradation of electrical characteristics compared to organic TFTs with a conventional TIPS-pentacene sole channel layer. [ABSTRACT FROM AUTHOR]

We found an abrupt reduction of contact resistance, Rc, in pentacene bottom-contact thin-film transistors (TFT's) with Au/Ti source/drain (S/D) electrodes when Ti thickness is below ∼3 nm. Our results suggest that the direct ohmic contact with a few molecular layer channel is a key to reduce the Rc of the S/D electrodes. We propose a Au/self-assembled monolayer electrode structure enabling direct ohmic contact with these few molecular layer channels, and achieved high-performance bottom-contact TFTs with an extrinsic mobility of 1.1 cm²/V s, an on/off ratio of 106, and a subthreshold swing of 0.3 V/decade. [ABSTRACT FROM AUTHOR]

JRAB/MICAL-L2 is an effector protein of Rab13, a member of the Rab family of small GTPase. JRAB/MICAL-L2 consists of a calponin homology domain, a LIM domain, and a coiled-coil domain. JRAB/MICAL-L2 engages in intramolecular interaction between the N-terminal LIM domain and the C-terminal coiled-coil domain, and changes its conformation from closed to open under the effect of Rab13. Open-form JRAB/MICAL-L2 induces the formation of peripheral ruffles via an interaction between its calponin homology domain and filamin. Here, we report that the LIM domain, independent of the C-terminus, is also necessary for the function of open-form JRAB/MICAL-L2. In mechanistic terms, two zinc finger domains within the LIM domain bind the first and second molecules of actin at the minus end, potentially inhibiting the depolymerization of actin filaments (F-actin). The first zinc finger domain also contributes to the intramolecular interaction of JRAB/MICAL-L2. Moreover, the residues of the first zinc finger domain that are responsible for the intramolecular interaction are also involved in the association with F-actin. Together, our findings show that the function of open-form JRAB/MICAL-L2 mediated by the LIM domain is fine-tuned by the intramolecular interaction between the first zinc finger domain and the C-terminal domain. [ABSTRACT FROM AUTHOR]

We demonstrate that activation-induced manganese-enhanced magnetic resonance imaging with quantitative determination of the longitudinal relaxation time (qAIM-MRI) reveals the severity of Parkinson's disease (PD) in mice. We first show that manganese ion-accumulation depends on neuronal activity. A highly active region was then observed by qAIM-MRI in the caudate-putamen in PD-model mice that was significantly correlated to the severity of PD, suggesting its involvement in the expression of PD symptoms. [ABSTRACT FROM AUTHOR]

Background: Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), shows multiple pharmacological actions such as inhibiting presynaptic α2 noradrenaline receptor (NAR) and selectively activating 5-hydroxytriptamine (5-HT) 1A receptor (5-HT1AR). Mirtazapine was also reported to increase dopamine release in the cortical neurons with 5-HT dependent manner. To examine whether mirtazapine has a therapeutic potency in Parkinson's disease (PD), we examined this compound in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model of PD.Results: Male C57BL/6 mice were subjected to MPTP treatment to establish a PD model. Mirtazapine was administered once a day for 3 days after MPTP treatment. MPTP-induced motor dysfunction, assessed by beam-walking and rota-rod tests, was significantly improved by administration of mirtazapine. Biochemical examinations by high performance liquid chromatography and western blot analysis suggested mirtazapine facilitated utilization of dopamine by increasing turnover and protein expression of transporters, without affecting on neurodegenerative process by MPTP. These therapeutic effects of mirtazapine were reduced by administration of WAY100635, an inhibitor for 5HT1AR, or of clonidine, a selective agonist for α2-NAR, or of prazosin, an inhibitor for α1-NAR, respectively.Conclusion: Our results showed mirtazapine had a therapeutic potency against PD in a mouse model. Because PD patients sometimes show depression together, it will be a useful drug for a future PD treatment. [ABSTRACT FROM AUTHOR]

A correction to the article "Therapeutic Effect of a Novel Anti-Parkinsonian Agent Zonisamide Against MPTP (1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine) Neurotoxicity in Mice," that was published in the January 12, 2011 issue is presented.