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Biomedical subjects

Shigeru Tanaka

Publications and source records attributed to Shigeru Tanaka.

At least 19 recordsLinked to original sources

Bcl2 enhances survival of newborn neurons in the normal and ischemic hippocampus.

Neuronal progenitors in the adult hippocampus continually proliferate and differentiate to the neuronal lineage, and ischemic insult promotes hippocampal neurogenesis. However, newborn neurons show a progressive reduction in numbers during the initial few weeks, therefore, enhanced survival of newborn neurons seems to be essential for therapeutic strategy. Bcl-2 is a crucial regulator of programmed cell death in CNS development and in apoptotic and necrotic cell death. Therefore, we tested whether Bcl-2 overexpression enhances survival of newborn neurons in the adult mouse hippocampus under normal and ischemic conditions. Many newborn neurons in the hippocampal dentate gyrus undergo apoptosis. Human Bcl-2 expression in NSE-bcl-2 transgenic mice began at the immature neuronal stage and remained constant in surviving mature neurons. Bcl-2 significantly increased survival of newborn neurons under both conditions, but particularly after ischemia, with decreased cell death of newborn neurons in NSE-bcl-2 transgenic mice. We also clarified the effect by Bcl-2 overexpression of enhanced survival of newborn neurons in primary hippocampal cultures with BrdU labeling. These findings suggest that Bcl-2 plays a crucial role in adult hippocampal neurogenesis under normal and ischemic conditions.

Animals↗

Chronically mountable goggles for persistent exposure to single orientation.

To examine the effect of experience on the developmental plasticity of functional maps in the visual cortex, we need to establish a method for a stable visual experience manipulation under the freely moving condition. For this purpose, we fabricated goggles that are chronically mounted stably on the animal's head, but easy to replace according to the animal's growth. Here we report the design of the goggles and the method of mounting them on the head of animals. By this method, combined with the intrinsic signal optical imaging technique, we were able to observe a rapid and robust reorganization of orientation maps.

Aging↗

A new planar multielectrode array: recording from a rat auditory cortex.

In the study of the spatiotemporal properties of the cortex, a demand often arises for recording local field evoked potentials (LFEP) and neural spikes from a quantity of points at close range from each other. In such a situation a device composed of a lot of electrodes assembled in a single bunch would be suitable. Such circumstances gave us the impetus to create the device described in this paper, namely a new planar electrode array for in vivo multisite extracellular recording. The device is made of plastic and includes platinum electrodes 50 microm in diameter. The array of 64 incorporated microelectrodes is placed on the surface of the cortex of anesthetized rats. Recordings could be made through all electrodes for more than 1 h without damage to the cortex. The inter-polar distance is approximately 100 microm so that each individual electrode can record activity from a separate population of neurons near the cortical surface. The recording system described here is highly useful for visualizing spatiotemporal structure of the cortical activities and for imaging dynamic neuronal assemblies.

Acoustic Stimulation↗

Synaptic efficacy cluster formation across the dendrite via STDP.

The role of spike-timing-dependent plasticity (STDP) in shaping the strength of a synapse located on the dendritic tree has gained recent interest. Previous theoretical studies using STDP have mostly used simplified integrate-and-fire models to investigate the evolution of synaptic efficacy with time. Such studies usually show that the final weight distribution is unimodal or bimodal resulting from a multiplicative or additive STDP rule, respectively. However, very little is known about how STDP shapes the spatial organization of synaptic efficacies. Here, for the first time, we demonstrate that spatial clustering of synaptic efficacies can occur on the dendrite via STDP, where changes in synaptic efficacy are driven by timing differences between synaptic inputs and the generation of local dendritic spikes. Specifically, when the model neuron is stimulated by two independent groups of correlated afferent inputs, the synaptic efficacies from each group, are not only spatially clustered on the dendrite but also spatially complementary to each other.

Action Potentials↗

Online analysis method for intrinsic signal optical imaging.

The intrinsic optical imaging technique has been widely applied for the visualization of functional maps in the sensory cortices of mammals. Many current studies refer this mapping in order to focus thereafter on particular features, at some particular locations: a fast and accurate mapping is therefore required. However, even during a successful experiment, the recorded raw data are usually contaminated by some kinds of noise that cannot necessarily be averaged out over the trials. An adequate image data analysis method has to be applied to extract signals closely related neural activities in response to presented stimuli. Thus far two different analysis methods could be adopted: the band-pass filtering and the GIF method [Yokoo T, Knight BW, Sirovich L. An optimization approach to signal extraction from noisy multivariate data. NeuroImage 2001:14;1309-26]. While the latter one is very efficient but requires the whole data in order to maximize the signal to noise ratio, the simple band-pass filtering technically reaches its limits very quickly. Here we propose another filtering method based on the polynomial subtraction of spatially smoothly modulated components. This simple method can visualize well-organized iso-orientation domains of the cat visual cortex with reliability similar to more sophisticated ones while allowing an online visualization of the clean data.

Action Potentials↗

Polycyclic aromatic hydrocarbons (PAHs) in the aerosol in Beijing, China, measured by aminopropylsilane chemically-bonded stationary-phase column chromatography and HPLC/fluorescence detection.

We developed a useful analytical method for the determination of polycyclic aromatic hydrocarbons (PAH) concentrations in the aerosol of China. We used an accelerated solvent extraction (ASE) method for the extraction of PAHs from the aerosol samples, in order to reduce the extraction time and the solvent volume used. The optimum purification method was developed, with aminopropylsilane chemically-bonded stationary-phase column chromatography, in order to remove many co-extractives which cannot be removed by conventional purification methods using silica-gel column chromatography. HPLC/fluorescence detection (FLD) was adopted as the analytical method, because it has very high sensitivity to PAH and it is easy to install, operate, and maintain as compared with GC/MS. With the analytical method developed in this study, the recovery and precision (RSD) for most of the PAHs ranged from 75% to 129% and from 2.8% to 22.7%, respectively. The concentrations of PAHs in the aerosol samples collected from October 2003 to April 2005 in Beijing, China were determined using the newly developed method. SigmaPAHs, which is the sum of the concentrations of all detected PAHs, was 177.8 +/- 239.9 ng m(-3) (n = 64). The SigmaPAHs concentration in the heating season (305.1 +/- 279.0 ng m(-3), n = 33) was 7.2 times higher than that in the non-heating season (42.3 +/- 32.0 ng m(-3), n = 31). These strong seasonal variations in atmospheric PAH concentration are possibly due to coal combustion for residential heating in winter.

Aerosols↗

Iridium complex-catalyzed [2+2+2] cycloaddition of alpha,omega-diynes with monoynes and monoenes.

[reaction: see text] [Ir(cod)Cl]2/DPPE was found to be a new catalyst for the cycloaddition of alpha,omega-diynes with monoynes to give polysubstituted benzene derivatives in high yields. Internal monoynes as well as terminal monoynes could be used. The reaction tolerates a broad range of functional groups such as alcohol, amine, alkene, ether, halogen, and nitrile. The reaction of 1,6-octadiyne derivatives with 1-alkynes gives ortho products and meta products. The regioselectivity could be controlled by the choice of ligand. The reaction with DPPE was meta selective, with meta selectivity of up to 82%. The reaction with DPPF was ortho selective, with ortho selectivity of up to 88%. We propose a mechanism to account for this regioselective cycloaddition. [Ir(cod)Cl](2)/DPPE also catalyzed the cycloaddition of alpha,omega-diynes with 2,5-dihydrofuran to give bicyclic cyclohexadiene derivatives. The reaction with 2,3-dihydrofuran and n-butyl vinyl ether gave benzene derivatives instead of cyclohexadiene derivatives. We also propose a mechanism to account for this novel aromatization that includes cleavage of the C-O bond.

Journal Article↗

Theoretical and experimental studies of relationship between pinwheel centers and ocular dominance columns in the visual cortex.

In the visual cortex, pinwheel centers, which appear as point singularities in orientation maps, are likely to be found at the centers of ocular dominance columns in normal cats and monkeys. To elucidate the mechanism underlying the geometrical relationship, we performed computer simulation based on our correlation-based self-organization model. The simulation showed that pinwheel centers tended to be located at the ocular dominance centers at higher correlations of activities between the left- and right-eye specific pathways, whereas they tended to appear along the borders of ocular dominance columns at lower correlations. This tendency was mathematically analyzed with a formula describing the condition determining the geometrical relationship between pinwheel centers and ocular dominance columns. Moreover, to examine the effect of activity correlations in the eye-specific pathways on the column formation, we conducted intrinsic signal optical imaging using normally reared cats and dark-reared cats. The between-eye activity correlation in dark-reared cats is expected to be lower than that in normal cats due to the lack of common visual input in the two eyes. The statistical analysis of experimental data showed that while more pinwheel centers tended to be located in the center subregion of ocular dominance columns than in the border subregion in the normal cats, a weak tendency in the opposite direction was found in the dark-reared cats. Based on the consistent results from the model and experiment, it is suggested that the activity correlation between the left- and right-eye specific pathways has influence on the establishment of geometrical relationship in the cortical representation between orientation preference and ocular dominance.

Animals↗

Preservation of functional architecture in visual cortex of cats with experimentally induced hydrocephalus.

We investigated how neural function is preserved or matured in the visual cortex of cats, following the induction of hydrocephalus by kaolin injection. In vivo optical imaging of intrinsic signals in 11-17-week-old hydrocephalic cats revealed orientation maps showing the orderly arrangement of preferred orientations when stimulated by grating stimuli at a low spatial frequency, whereas stimulus-evoked intrinsic signals in response to gratings at a high spatial frequency were often too weak to construct orientation maps. Furthermore, in two of the three hydrocephalic cats, initially deteriorated orientation maps became almost regular maps in the second imaging experiments conducted 8 and 11 weeks, respectively, after the first imaging. This indicates that, despite large structural deformation of the hydrocephalic brain, orientation maps are elaborated sufficiently after the age of 5-6 months, by which time the orientation map formation is usually completed in normal cats. Single unit recording from the decompressed visual cortex revealed that many neurons showed normal orientation selectivity, whereas the binocularity of these neurons was found to be reduced. These results suggested that the deformed visual cortex of hydrocephalic cats exhibits a high plasticity, retaining its functional organization.

Action Potentials↗

Analytical solutions for nonlinear cable equations with calcium dynamics. I: Derivations.

The interaction between membrane potential and internal calcium concentration plays many important roles in regulating synaptic integration and neuronal firing. In order to gain a better theoretical understanding between the voltage-calcium interaction, a nonlinear cable equation with calcium dynamics is solved analytically. This general reaction-diffusion system represents a model of a cylindrical dendritic segment in which calcium diffuses internally in the presence of buffers, pumps and exchangers, and where ion channels are sparsely distributed over the membrane,in the form of hotspots, acting as point current sources along the dendritic membrane. In order to proceed, the reaction-diffusion system is recast into a system of coupled nonlinear integral equations, with which a perturbative expansion in dimensionless voltage and calcium concentration are used to find analytical solutions to this general system. The resulting solutions can be used to investigate, the interaction between the membrane potential and underlying calcium dynamics in a natural (non-discretized) setting.

Animals↗

Cavitating invasive pulmonary aspergillosis visualized and diagnosed by ultrathin bronchoscopy.

A definitive diagnosis of invasive pulmonary aspergillosis (IPA), which usually occurs in immunocompromised patients, is often difficult. We report two cases of cavitating IPA in a peripheral pulmonary region in patients who were receiving corticosteroids, in whom the cavity was successfully visualized and sampled during ultrathin bronchoscopy. Ultrathin bronchoscopy provides a new option for definitive diagnosis of cavitating IPA.

Aged↗

[Characteristics of polycyclic aromatic hydrocarbons (PAHS) on airborne particulates in Beijing].

Total suspended particulates (TSP) samples were collected from Sep., 2003 to Jul., 2004 in Beijing, and 15 kinds of PAHs, ranging from 3 to 7 rings were analyzed. The maximum concentrations sigma PAHs and BaP were 705 ng/m3 and 52 ng/m3 respectively. Average sigma PAHs concentrations in four seasons were 46 ng/m3, 16 ng/m3, 52 ng/m3 and 268 ng/m3 respectively; and the average BaP concentrations in four seasons were 2.8 ng/m3, 0.23 ng/m3, 3.3 ng/m3, 16 ng/m3 respectively. Regarding to the meteorological parameters, precipitation distinctly lowered the concentration; in heating period, PAHs concentrations fall with the temperature goes up, but there is no obvious relation between concentration and temperature in non-heating period; the increase of wind speed level causes the decrease of PAH concentrations in the heating period, but relation between PAH concentrations and wind speed varied with aromatic rings of PAHs and levels of wind speed in the non-heating period.

Air Pollutants↗

Orientation-restricted continuous visual exposure induces marked reorganization of orientation maps in early life.

To elucidate the effect of visual experience on the development of orientation maps, we conducted intrinsic signal optical imaging of the visual cortex of kittens that were continuously exposed to a single orientation through cylindrical-lens-fitted goggles under a freely moving condition starting at post-natal week 3. We observed a rapid reorganization of orientation maps, characterized by extensive representation of exposed orientations with reduced responsiveness to unexposed orientations. The over-representation of exposed orientation was marked for 1-2 weeks of goggle rearing. A longer period of goggle rearing, however, decreased the degree of over-representation, which still remained at a remarkable level. Dark rearing episodes daily interleaved between single orientation exposures moderated the over-representation effect. Unit recording from goggle-reared kittens showed preferred orientations consistent with optical imaging. Using c-Fos immunoreactivity mapping, we showed that the number of neurons strongly responding to the exposed orientation was 3 times larger in a goggle-reared cat than the number of neurons responding to the vertical orientation in a normal cat. Taken together, these results suggest that the reorganization of orientation maps was caused by the expansion of domains maximally responding to exposed orientation as well as the strong reduction of responses to unexposed orientations.

Algorithms↗

Regulation of meiotic prophase arrest in mouse oocytes by GPR3, a constitutive activator of the Gs G protein.

The arrest of meiotic prophase in mouse oocytes within antral follicles requires the G protein G(s) and an orphan member of the G protein-coupled receptor family, GPR3. To determine whether GPR3 activates G(s), the localization of Galpha(s) in follicle-enclosed oocytes from Gpr3(+/+) and Gpr3(-/-) mice was compared by using immunofluorescence and Galpha(s)GFP. GPR3 decreased the ratio of Galpha(s) in the oocyte plasma membrane versus the cytoplasm and also decreased the amount of Galpha(s) in the oocyte. Both of these properties indicate that GPR3 activates G(s). The follicle cells around the oocyte are also necessary to keep the oocyte in prophase, suggesting that they might activate GPR3. However, GPR3-dependent G(s) activity was similar in follicle-enclosed and follicle-free oocytes. Thus, the maintenance of prophase arrest depends on the constitutive activity of GPR3 in the oocyte, and the follicle cell signal acts by a means other than increasing GPR3 activity.

Animals↗

Spatial patterns of excitation and inhibition evoked by lateral connectivity in layer 2/3 of rat barrel cortex.

In the rat barrel cortex, neurons in layer 4 are topographically arranged in a precise columnar structure, and the excitatory feed-forward input from layer 4 to layer 2/3 projects almost exclusively within the home barrel column. Here we analyzed the lateral connectivity that links neighboring columns in layer 2/3, which is necessary for integrating information across whiskers. We examined the spatial distributions of three different functional types of lateral connections in layer 2/3 of the rat barrel cortex: glutamate receptor-mediated excitatory connections, GABA(A) receptor-mediated inhibitory connections and GABA(B) receptor-mediated inhibitory connections. Synaptic potentials of pyramidal neurons, which are measures of the strength of connections, were evoked by a horizontal array of stimulation electrodes. The synaptic potentials and their decrease with distance from the stimulation site were measured in two types of slices whose planes were parallel to or orthogonal to barrel rows. Excitatory and GABA(B) receptor-mediated inhibitory connections were stronger along barrel rows than across them, whereas GABA(A) receptor-mediated inhibitory connections did not show such a tendency. These results indicate that lateral connectivity in layer 2/3 varies on the basis of not only excitatory polarity but also receptor subtypes.

Animals↗

Adenovirus-mediated gene transfer of heparin-binding epidermal growth factor-like growth factor enhances neurogenesis and angiogenesis after focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: Recent studies have demonstrated that neurotrophic factors promote neurogenesis after cerebral ischemia. However, it remains unknown whether administration of genes encoding those factors could promote neural regeneration in the striatum and functional recovery. Here, we examined the efficacy of intraventricular injection of a recombinant adenovirus-expressing heparin-binding epidermal growth factor-like growth factor (HB-EGF) on neurogenesis, angiogenesis, and functional outcome after focal cerebral ischemia. METHODS: Transient focal ischemia was induced by middle cerebral artery occlusion (MCAO) for 80 minutes with a nylon filament in Wistar rats. Three days after MCAO, either adenovirus-expressing HB-EGF (Ad-HB-EGF) or Ad-LacZ, the control vector, was injected into the lateral ventricle on the ischemic side. Bromodeoxyuridine (BrdU) was injected intraperitoneally twice daily on the sixth and seventh days. On the eighth or 28th day after MCAO, we evaluated infarct volume, neurogenesis, and angiogenesis histologically. Neurological outcome was serially evaluated by the rotarod test after MCAO. RESULTS: There was no significant difference in infarct volume between the 2 groups. Treatment with Ad-HB-EGF significantly increased the number of BrdU-positive cells in the subventricular zone on the 8th day. In addition, on the 28th day, BrdU-positive cells differentiated into mature neurons in the striatum on the ischemic side but seldom the cells given Ad-LacZ. Enhancement of angiogenesis at the peri-infarct striatum was also observed on the eighth day in Ad-HB-EGF-treated rats. Treatment with Ad-HB-EGF significantly enhanced functional recovery after MCAO. CONCLUSIONS: Our data suggest that gene therapy using Ad-HB-EGF contributes to functional recovery after ischemic stroke by promoting neurogenesis and angiogenesis.

Adenoviridae↗

Long-term trend of chemical constituents in precipitation in Tokyo metropolitan area, Japan, from 1990 to 2002.

In order to understand the actual status and mechanism of acid rain, it is important to know the pH of precipitation and its chemical constituents on a continuous and regular basis over a wide area. This study examines acid rain over a wide area using an observational network in the Tokyo metropolitan area of Japan, and analyzes the major chemical constituents of every precipitation sample. Precipitation was collected continuously for a period of 12 years from June 1990 to May 2002 at several sampling sites in the Tokyo metropolitan area, and its pH and chemical constituent concentrations were measured. The average pH ranged from 4.23 to 4.62, clearly indicating acidification of precipitation over the entire Tokyo metropolitan area. A time-trend model was applied to describe temporal variations of chemical constituent concentrations, including annual change rate, seasonal variation, and precipitation effects. Seasonal and annual trends for the past 12 years were examined with the model, using the least squares method. Nonsea salt (nss)-Ca2+ shows a maximum value in early spring, a seasonality probably caused by calcium-rich particles in airborne yellow dust from Asia. Slightly decreasing annual trends of nss-SO4(2-) may correspond to the recent decreasing trend of atmospheric SO2 gas concentrations in the Tokyo metropolitan area. The annual trends of NO3-, NH4+, and nss-Ca2+ show a large site-to-site difference. The increasing NO3-, NH4+, and nss-Ca2+ concentrations at inland suburban sites may be caused by increases in their local sources such as vehicle traffic and municipal waste incineration. The annual change rate of H+ is slightly negative or almost zero at every site, so the acidification of precipitation has not become worse since 1990 over the Tokyo metropolitan area.

Journal Article↗

Neural modeling of an internal clock.

We studied a simple random recurrent inhibitory network. Despite its simplicity, the dynamics was so rich that activity patterns of neurons evolved with time without recurrence due to random recurrent connections among neurons. The sequence of activity patterns was generated by the trigger of an external signal, and the generation was stable against noise. Moreover, the same sequence was reproducible using a strong transient signal, that is, the sequence generation could be reset. Therefore, a time passage from the trigger of an external signal could be represented by the sequence of activity patterns, suggesting that this model could work as an internal clock. The model could generate different sequences of activity patterns by providing different external signals; thus, spatiotemporal information could be represented by this model. Moreover, it was possible to speed up and slow down the sequence generation.

Action Potentials↗