β-Amyrenonol/Olean-12-en-11-one, 3-hydroxy-, (3β)-/b-Amyrenonol/(3β)-3-Hydroxyolean-12-en-11-one/11-oxo-β-amyrin
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provides coniferyl ferulate(CAS#:38242-02-3) MSDS, density, melting point, boiling point, structure, formula, molecular weight etc. Articles of coniferyl ferulate are included as well.>> amp version: coniferyl ferulate
Evidence for different physiological properties along the hippocampal longitudinal axis is emerging. Here, we examined the electrophysiological features of neurons at different dorso-ventral sites of the mouse CA1 hippocampal region. Cell position was defined with respect to longitudinal coordinates of each slice. We measured variations in neuronal excitability, subthreshold membrane properties and neurotransmitter responses along the longitudinal axis. We found that (i) pyramidal cells of the dorsal hippocampus (DH) were less excitable than those of the ventral hippocampus (VH). Resting Membrane Potential (RMP) was more hyperpolarized and somatic Input Resistance (Ri) was lower in DH compared to VH. (ii) The Paired-pulse ratio (PPR) of focally induced synaptic responses was systematically reduced from the DH to the VH; (iii) Long-term-potentiation was most pronounced in the DH and fell gradually in the intermediate hippocampus and in the VH; (iv) the frequency of miniature GABAergic events was higher in the VH than in the DH; (v) the PPR of evoked inhibitory post-synaptic current (IPSC) was higher in the DH than in the VH. These findings indicate an increased probability of both GABA and glutamate release and a reduced plasticity in the ventral compared to more dorsal regions of the hippocampus.
The hippocampus is a medial temporal lobe structure widely studied for its unique role in learning and memory. In the rodent brain, the hippocampus is an elongated structure with a longitudinal axis extending in a C-shaped fashion from dorsal (septal)-to-ventral (temporal), corresponding to a posterior-to-anterior axis in human1. While intrinsic circuitry is conserved along the longitudinal axis, dorsal and ventral regions have different connectivity with cortical and subcortical areas. The dorsal hippocampus receives visual and spatial information from sensory cortices via the medial entorhinal cortex. In contrast, ventral hippocampus is connected to the amygdala, prefrontal cortex (PFC) and hypothalamus2,3,4. Previous studies based on targeted lesions, electrophysiological recording and selective pharmacological blockade suggest that dorsal regions serve mainly cognitive functions, including spatial and declarative memory, while ventral regions are involved in regulating emotional responses5,6.
Several studies based on gene expression, anatomical and behavioral measurements have suggested that the hippocampus has different functional organizations along its longitudinal axis. In particular, it has been proposed that either this brain region is organized in multiple functional domains or it is structured according to a spatial gradient2,5,7,8,9. Recently, it has been proposed a model in which functional long-axis gradients are superimposed on tripartite functional domains: ventral (VH), intermediate (IH) and dorsal (DH) regions1.
Longitudinal variations in the electrophysiology of hippocampal neurons have been already investigated in the rat. CA1 pyramidal cells have been reported to be more excitable in the ventral compared to the dorsal region10,11. In addition, the short- and long-term plasticity of synapses terminating on DH and VH neurons differs both in vivo12 and in vitro13,14,15,16. Specifically, paired pulse facilitation (PPF), a short-term synaptic plasticity depending on changes in transmitter release17, is weaker in VH than in DH12,15, suggesting that basal transmitter release probability may be higher in VH. Furthermore, the magnitude of long-term potentiation (LTP)18 elicited in the VH is significantly smaller than that induced in both DH14,16 and IH19. Though these results provide an electrophysiological characterization along the hippocampal longitudinal axis in the rat, only very limited amount of data is available for the mouse20, prompting the need to extend the study also to this species.
In the present study, we investigated in the mouse the electrophysiological properties of CA1 pyramidal cells along the hippocampal longitudinal axis. Neuronal properties, including subthreshold membrane behavior and firing activity, as well as short- and long-term plasticity at synapses that excites these cells were assessed. Furthermore, we examined for the first time the inhibitory GABAergic synaptic function in DH and VH. To this purpose, we exploited an experimental strategy, based on isolating and straightening the hippocampus, to determine the coordinates of the neurons along the dorsal to ventral axis.
Electrophysiological Properties of CA1 Pyramidal Neurons along the Longitudinal Axis of the Mouse Hippocampus
Giampaolo Milior,1,2 Maria Amalia Di Castro,1 Livio Pepe’ Sciarria,1 Stefano Garofalo,1 Igor Branchi,3 Davide Ragozzino,1,4 Cristina Limatola,1,4 and Laura Maggia,1
Multiple factors have been implicated in the age-related declines in brain function. Thus, it is unlikely that modulating only a single factor will be effective at slowing this decline. A better approach is to identify small molecules that have multiple biological activities relevant to the maintenance of brain function. Over the last few years, we have identified an orally active, novel neuroprotective and cognition-enhancing molecule, the flavonoid fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also maintain mitochondrial function in the presence of oxidative stress. In addition, it has anti-inflammatory activity against microglial cells and inhibits the activity of 5-lipoxygenase, thereby reducing the production of lipid peroxides and their pro-inflammatory by-products. This wide range of actions suggests that fisetin has the ability to reduce the age-related decline in brain function.
Oxidative stress, Glutathione, Nrf2, Memory, Microglia
Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin
Polycyclic aromatic hydrocarbons (PAHs) are activated by cytochrome P450 (CYP) isozymes, and a subset of the reactive metabolites generated is detoxified via conjugation with glutathione (GSH) by specific glutathione S-transferases (GSTs). We have used V79MZ cells stably transfected with either human or rat cytochrome P4501A1 (CYP1A1), alone or in combination with human GSTP1 (hGSTP1), to examine the dynamics of activation versus detoxification of benzo[a]pyrene (B[a]P), dibenzo[a,l]pyrene (DB[a,l]P), and their dihydrodiol metabolites. The cytotoxicity of B[a]P or DB[a,l]P was 9- to 11-fold greater in cells expressing human, as compared to rat CYP1A1, despite similar enzymatic activities. Co-expression of the hGSTP1 with the hCYP1A1 conferred 16-fold resistance to B[a]P cytotoxicity, compared to only 2.5-fold resistance when hGSTP1 was co-expressed with rat CYP1A1. The lower B[a]P cytotoxicity in the cells expressing rat CYP1A1, and weaker protection by hGSTP1 co-expression in these cells, were attributable to the much lower fraction of B[a]P metabolism via formation of the 7,8-dihydrodiol intermediate by the rat CYP1A1 compared to hCYP1A1. Resistance to the DB[a,l]P cytotoxicity conferred by hGSTP1 expression was also greater in cells co-expressing hCYP1A1 (7-fold) as compared to cells co-expressing rCYP1A1 (< 2-fold). Resistance to B[a]P conferred by hGSTP1 was closely correlated with the activity level in two clonal transfectant lines with a 3-fold difference in hGSTP1-1 specific activity. Depletion of GSH to 20% of control levels via pretreatment with the de novo GSH biosynthesis inhibitor buthionine sulfoximine reduced the protection against B[a]P cytotoxicity by hGSTP1 from 16-fold to 5-fold, indicating that catalysis of conjugation with GSH, rather than binding or other effects, is responsible for the resistance. The cytotoxicity of the dihydrodiol intermediates of B[a]P or DB[a,l]P was much greater, and similar in cell lines expressing either human or rat CYP1A1. Again, however, the protection conferred by hGSTP1 co-expression was 2- to 5-fold greater in cells with hCYP1A1 than with rCYP1A1 expression. These results indicate that GST expression can effectively limit cytotoxicity following activation of B[a]P by human or rat CYP1A1, but is less effective as a defense against exposure of cells to the intermediate metabolite B[a]P-7,8-dihydrodiol.
glutathione S-transferase, cytochrome P-450, benzo[a]pyrene, dibenzo[al]pyrene, polycyclic aromatic hydrocarbon, carcinogen detoxification, transfection
Differential protection by human glutathione S-transferase P1 against cytotoxicity of benzo[a]pyrene, dibenzo[a,l]pyrene, or their dihydrodiol metabolites, in bi-transgenic cell lines that co-express rat versus human cytochrome P4501A1
Sandra L. Kabler,1 Albrecht Seidel,2 Juergen Jacob,2 Johannes Doehmer,3 Charles S. Morrow,1 and Alan J. Townsend1,*
2010 May 15