Green Tea-Derived Catechins Have Beneficial Effects on Cognition in the Pond Snail

Green tea has been used as a medicine in East Asia for thousands of years. Plant-derived compounds called flavanols, which are included in green tea, may have potentials to help maintain healthy brain function. In this chapter, we review the effects of flavanols, e.g. epicatechin (EpiC), on cognitive ability in the pond snail, Lymnaea stagnalis. In this decade, the Lukowiak’s group has tested the effects of EpiC on cognition ability in Lymnaea. In a Lymnaea model system, they showed that EpiC and EpiC-containing foods have a rapid and activity-dependent effect enhancing the formation of long-term memory (LTM) following operant conditioning of aerial respiratory behavior. In the last part of this chapter, we also introduce our study for the effects of EpiC on LTM formation in another model system in Lymnaea. This study showed that EpiC increases the persistence of LTM formed by classical conditioning of feeding behavior, and suggested that EpiC alters some electrophysiological properties of a neuron in the feeding system

Corticosterone Induces Rapid Spinogenesis via Synaptic Glucocorticoid Receptors and Kinase Networks in Hippocampus

BACKGROUND: Modulation of dendritic spines under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT) secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrated the mechanisms of rapid effect (∼1 h) of CORT on the density and morphology of spines by imaging neurons in adult male rat hippocampal slices. The application of CORT at 100-1000 nM induced a rapid increase in the density of spines of CA1 pyramidal neurons. The density of small-head spines (0.2-0.4 µm) was increased even at low CORT levels (100-200 nM). The density of middle-head spines (0.4-0.5 µm) was increased at high CORT levels between 400-1000 nM. The density of large-head spines (0.5-1.0 µm) was increased only at 1000 nM CORT. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR), abolished the effect of CORT. Blocking a single kinase, such as MAPK, PKA, PKC or PI3K, suppressed CORT-induced enhancement of spinogenesis. Blocking NMDA receptors suppressed the CORT effect. CONCLUSIONS/SIGNIFICANCE: These results imply that stress levels of CORT (100-1000 nM) drive the spinogenesis via synaptic GR and multiple kinase pathways

Endogenous Synthesis of Corticosteroids in the Hippocampus

BACKGROUND: Brain synthesis of steroids including sex-steroids is attracting much attention. The endogenous synthesis of corticosteroids in the hippocampus, however, has been doubted because of the inability to detect deoxycorticosterone (DOC) synthase, cytochrome P450(c21). METHODOLOGY/PRINCIPAL FINDINGS: The expression of P450(c21) was demonstrated using mRNA analysis and immmunogold electron microscopic analysis in the adult male rat hippocampus. DOC production from progesterone (PROG) was demonstrated by metabolism analysis of (3)H-steroids. All the enzymes required for corticosteroid synthesis including P450(c21), P450(2D4), P450(11β1) and 3β-hydroxysteroid dehydrogenase (3β-HSD) were localized in the hippocampal principal neurons as shown via in situ hybridization and immunoelectron microscopic analysis. Accurate corticosteroid concentrations in rat hippocampus were determined by liquid chromatography-tandem mass spectrometry. In adrenalectomized rats, net hippocampus-synthesized corticosterone (CORT) and DOC were determined to 6.9 and 5.8 nM, respectively. Enhanced spinogenesis was observed in the hippocampus following application of low nanomolar (10 nM) doses of CORT for 1 h. CONCLUSIONS/SIGNIFICANCE: These results imply the complete pathway of corticosteroid synthesis of 'pregnenolone →PROG→DOC→CORT' in the hippocampal neurons. Both P450(c21) and P450(2D4) can catalyze conversion of PROG to DOC. The low nanomolar level of CORT synthesized in hippocampal neurons may play a role in modulation of synaptic plasticity, in contrast to the stress effects by micromolar CORT from adrenal glands

CO Multi-line Imaging of Nearby Galaxies (COMING). III. Dynamical effect on molecular gas density and star formation in the barred spiral galaxy NGC 4303

We present the results of $^{12}$CO($J$=1-0) and $^{13}$CO($J$=1-0) simultaneous mappings toward the nearby barred spiral galaxy NGC 4303 as a part of the CO Multi-line Imaging of Nearby Galaxies (COMING) project. Barred spiral galaxies often show lower star-formation efficiency (SFE) in their bar region compared to the spiral arms. In this paper, we examine the relation between the SFEs and the volume densities of molecular gas $n(\rm{H}_2)$ in the eight different regions within the galactic disk with CO data combined with archival far-ultraviolet and 24 $\mu$m data. We confirmed that SFE in the bar region is lower by 39% than that in the spiral arms. Moreover, velocity-alignment stacking analysis was performed for the spectra in the individual regions. The integrated intensity ratios of $^{12}$CO to $^{13}$CO ($R_{12/13}$) range from 10 to 17 as the results of stacking. Fixing a kinetic temperature of molecular gas, $n(\rm{H}_2)$ was derived from $R_{12/13}$ via non-local thermodynamic equilibrium (non-LTE) analysis. The density $n(\rm{H}_2)$ in the bar is lower by 31-37% than that in the arms and there is a rather tight positive correlation between SFEs and $n(\rm{H}_2)$, with a correlation coefficient of $\sim 0.8$. Furthermore, we found a dependence of $n(\rm{H}_2)$ on the velocity dispersion of inter-molecular clouds ($\Delta V/ \sin i$). Specifically, $n(\rm{H}_2)$ increases as $\Delta V/ \sin i$ increases when $\Delta V/ \sin i < 100$ km s$^{-1}$. On the other hand, $n(\rm{H}_2)$ decreases as $\Delta V/ \sin i$ increases when $\Delta V/ \sin i > 100$ km s$^{-1}$. These relations indicate that the variations of SFE could be caused by the volume densities of molecular gas, and the volume densities could be governed by the dynamical influence such as cloud-cloud collisions, shear and enhanced inner-cloud turbulence.Comment: 15 pages, 8 figures, accepted for publication in PAS

CO Multi-line Imaging of Nearby Galaxies (COMING) IV. Overview of the Project

Observations of the molecular gas in galaxies are vital to understanding the evolution and star-forming histories of galaxies. However, galaxies with molecular gas maps of their whole discs having sufficient resolution to distinguish galactic structures are severely lacking. Millimeter wavelength studies at a high angular resolution across multiple lines and transitions are particularly needed, severely limiting our ability to infer the universal properties of molecular gas in galaxies. Hence, we conducted a legacy project with the 45 m telescope of the Nobeyama Radio Observatory, called the CO Multi-line Imaging of Nearby Galaxies (COMING), which simultaneously observed 147 galaxies with high far-infrared flux in $^{12}$CO, $^{13}$CO, and C$^{18}$O $J=1-0$ lines. The total molecular gas mass was derived using the standard CO-to-H$_2$ conversion factor and found to be positively correlated with the total stellar mass derived from the WISE $3.4 \mu$m band data. The fraction of the total molecular gas mass to the total stellar mass in galaxies does not depend on their Hubble types nor the existence of a galactic bar, although when galaxies in individual morphological types are investigated separately, the fraction seems to decrease with the total stellar mass in early-type galaxies and vice versa in late-type galaxies. No differences in the distribution of the total molecular gas mass, stellar mass, and the total molecular gas to stellar mass ratio was observed between barred and non-barred galaxies, which is likely the result of our sample selection criteria, in that we prioritized observing FIR bright (and thus molecular gas-rich) galaxies.Comment: Accepted for publication in PASJ; 47 pages, 5 tables, 29 figures. On-line supplementary images are available at this URL (https://astro3.sci.hokudai.ac.jp/~radio/coming/publications/). CO data is available at the Japanese Virtual Observatory (JVO) website (https://jvo.nao.ac.jp/portal/nobeyama/coming.do) and the project website (https://astro3.sci.hokudai.ac.jp/~radio/coming/data/

Spine density of hippocampal CA1 neurons in sham rat (Control) or adrenalectomized rat (ADX).

<p>(A) Total spine density. For both sham and ADX rats, slices are incubated for 1 h in ACSF without drugs. The Total spine density was not different significantly between Control and ADX rats. (B) Histogram of spine head diameters. Abbreviations are same as in (A). After a 1 h treatment in ACSF without drugs for sham rat (Control, open circle) and ADX (closed black circle). (C) Density of three subtypes of spines. From left to right, small-head spines (small), middle-head spines (middle), and large-head spines (large). Abbreviations are same as in (A). Control (open column) and ADX (black column). Vertical axis is the average number of spines per 1 µm of dendrite. In (A) and (C) results are reported as mean ± SEM. The significance was examined using the Tukey–Kramer <i>post hoc</i> multiple comparisons test when one way ANOVA tests yielded <i>P</i><0.05. For sham and ADX rats, we investigated 3 rats, 6 slices, 12 neurons, 24 dendrites and approx. 1300 spines.</p

Effects of blockers of receptors on changes by CORT in the density and morphology of spines.

<p>(A) Effects of treatments by 1 µM CORT and blockers of receptors on the total spine density in CA1 neurons. A 1 h treatment in ACSF without drugs (Control), with 1 µM CORT (CORT), with 1 µM and 10 µM RU486 (CORT + RU), with 1 µM CORT and 50 µM MK-801 (CORT + MK), with 1 µM CORT and 20 µM CNQX (CORT + CNQX). (B) Histogram of spine head diameters after a 1 h treatment in ACSF without drugs (Control, open circle), with 1 µM CORT (CORT, closed black circle), and with 1 µM CORT and 10 µM RU486 (CORT + RU, closed red circle), with 1 µM CORT and 50 µM MK-801 (CORT + MK, closed blue circle), with 1 µM CORT and 20 µM CNQX (CORT + CNQX, closed green circle). Small-head spines (small), middle-head spines (middle), and large-head spines (large) are categorized. (C) Density of three subtypes of spines. Abbreviations are same as in (B). ACSF without drugs (open column), CORT (black column), CORT + RU (red column), CORT + MK (blue column), and CORT + CNQX (green column) are shown. (D) No effect of receptor inhibitors alone on the total spine density in CA1 neurons. Abbreviations are the same as in (A). Vertical axis is the average number of spines per 1 µm of dendrite. In (A) and (C), results are reported as mean ± SEM. In (A) and (C), the significance of CORT or drug effect was examined using the Tukey–Kramer <i>post hoc</i> multiple comparisons test when one way ANOVA tests yielded <i>P</i><0.05. *<i>P</i><0.05, **<i>P</i><0.01. For each drug treatment, we investigated 3 rats, 7 slices, 14 neurons, 28 dendrites and 1400–2000 spines, except for CORT which consists of 10 rats, 28 slices, 56 neurons, 113 dendrites and approx. 8000 spines. For control, we used 5 rats, 8 slices, 16 neurons, 31 dendrites and approx. 1700 spines.</p