TRPV1 受体调控海马突触可塑性的机制及其功能意义

全世界有四分之一人口的日常饮食中包含辣椒及其相关食品，辣椒素是辣椒 里使人产生辛辣和呛感觉的主要成分。辣椒素受体最初是在感觉神经元克隆到 的，后来被命名为TRPV1，是因为发现它属于TRP（Transient receptor potential，瞬时受体势）离子通道家族。辣椒素及其受体在疼痛学领域已有广 泛的研究，但它们如何调节脑功能却知之甚少。很多报道显示辣椒素受体在脑内 广泛表达。在啮齿类动物的海马内，辣椒素受体从齿状回到CA3-CA1区均有表达。 在亚细胞层次，辣椒素受体在神经元胞体，树突棘和突触部位均有表达。近年来 辣椒素受体的内源性配体也被发现，包括花生四烯酸乙醇胺（anandamide, AEA）、 氮磷脂-多巴胺(N-arachidonoyl-dopamine, NADA)、 精胺等。辣椒素在很多脑 区（包括海马），可通过其受体调节神经元兴奋性和神经递质释放。 海马双向突触可塑性，长时程增强(LTP)和抑制现象(LTD)被认为是学习与记 忆的细胞机制。而LTP/LTD的诱导阈值是由 NMDA受体的激活程度及其引起的突 触后胞内钙水平决定的。因此调节NMDA受体和胞内钙信号被认为是调节LTP/LTD 诱导阈值最直接有效的方式。考虑到辣椒素受体的突触分布及其对钙离子的高通 透性，我们认为辣椒素受体的激活可能参与调节LTP/LTD的诱导阈值 本研究采用离体脑片场电位记录方式，发现辣椒素易化LTP的诱导而损伤了 LTD的诱导，并且降低了LTP/LTD的诱导阈值。在给予辣椒素受体的拮抗剂以后， 或者是在TRPV1基因敲除小鼠的脑片上，辣椒素对LTP/LTD的诱导均没有影响。 我们发现的辣椒素对LTP/LTD的影响与行为学应激对LTP/LTD的影响，两者效应恰恰相反，应激是易化LTD的诱导而损伤LTP的诱导。如期所料，辣椒素使应激 损伤的LTP恢复，同时阻断了应激易化的LTD。除了对LTP/LTD有重要的调节作 用以外，我们的结果也显示应激严重损伤了动物对空间记忆的提取。所以我们进 一步研究辣椒素能否对抗应激对动物空间记忆的损伤。我们发现海马内埋置导管 给予辣椒素可以使应激损伤的空间记忆得到恢复，同样，灌胃给予辣椒素也可以 对抗应激对动物空间记忆的损伤，进一步提示日常饮食中的辣椒会对应激相关的 精神障碍有潜在的正面影响。 从动物实验到临床实验都有广泛的证据表明应激对认知功能，焦虑，创伤后 应激综合症等有着深刻的影响。综上所述，我们第一次报道了辣椒素通过激活 TRPV1受体可以对抗应激引起的空间记忆损伤，该效应可能是通过调节LTP/LTD 的诱导阈值来实现的。我们工作的意义在于揭示了辣椒素受体在应激相关的精神 疾病中的潜在作用，为寻找治疗应激相关的精神心理障碍提供了新的靶点，也为 辣椒偏好的饮食习惯与精神卫生之间的关系研究提供了新的思路。

On the chemical synthesis and drug delivery response of folate receptor-activated, polyethylene glycol-functionalized magnetite nanoparticles

We describe here the chemical synthesis and in vitro drug delivery response of polyethylene glycol (PEG)-functionalized magnetite (Fe3O4) nanoparticles, which were activated with a stable ligand, folic acid, and conjugated with an anticancer drug, doxorubicin. The functionalization and conjugation steps in the chemical synthesis were confirmed using Fourier transform infrared spectroscopy. The drug-release behavior of PEG-functionalized and folic acid-doxorubicin-conjugated magnetic nanoparticles was characterized by two stages involving an initial rapid release, followed by a controlled release. (C) 2007 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Simultaneous electrochemical determination of dopamine, uric acid and ascorbic acid using palladium nanoparticle-loaded carbon nanofibers modified electrode

Palladium nanoparticle-loaded carbon nanofibers (Pd/CNFs) were prepared by electrospinning and subsequent thermal treatment processes. Pd/CNFs modified carbon paste electrode (Pd/CNF-CPE) displayed excellent electrochemical catalytic activities towards dopamine (DA), uric acid (UA) and ascorbic acid (AA). The oxidation overpotentials of DA, UA and AA were decreased significantly compared with those obtained at the bare CPE. Differential pulse voltammetry was used for the simultaneous determination of DA, UA and AA in their ternary mixture.

Simultaneous determination of dopamine, ascorbic acid and uric acid with electrospun carbon nanofibers modified electrode

A novel carbon-nanofiber-modified carbon-paste electrode (CNF-CPE) was employed for the simultaneous determination of dopamine (DA), ascorbic acid (AA) and uric acid (UA) with good selectivity and high sensitivity. The CNFs were prepared by combination of electrospinning technique with thermal treatment method and were used without any pretreatment. In application to determination of DA, AA and UA in the ternary mixture, the pristine CNF-CPE exhibited well-separated differential pulse voltammetric peaks with high catalytic current. Low detection limits of 0.04 mu M, 2 mu M and 0.2 mu M for DA, AA and UA were obtained, with the linear calibration curves over the concentration range 0.04-5.6 mu M, 2-64 mu M and 0.8-16.8 mu M, respectively.

Simultaneous electrochemical determination of uric acid, dopamine, and ascorbic acid at single-walled carbon nanohorn modified glassy carbon electrode

Single-walled carbon nanohorn modified glassy carbon electrode (SWCNH-modified GCE) was first employed for the simultaneous determination of uric acid (UA), dopamine (DA), and ascorbic acid (AA). The SWCNH-modified GCE displayed excellent electrochemical catalytic activities. The oxidation overpotentials of UA, DA, and AA decrease significantly and their oxidation peak currents increase dramatically at SWCNH-modified GCE. Linear sweep voltammetry (LSV) was used for the simultaneous determination of UA, DA, and AA in their ternary mixture. The peak separations between UA and DA, and DA and AA are large up to 152 mV and 221 mV, respectively.

Surface-Relevant Regulable DNA Toroids Induced by Dopamine

Dopamine (2-(3,4-dihydroxyphenyl)ethylamine) is known as a natural chemical neurotransmitter and is also a cytotoxic and genotoxic molecule for cell apoptosis. In this work, the interaction of DNA with dopamine was investigated. Though the electrostatic interaction of DNA and dopamine was weak in aqueous solution, dopamine condensed circular pBR322 DNA into toroids on the mica surface cooperatively with ethanol. The formed DNA toroids came from the shrinking of DNA that was driven by ethanol-enhanced DNA-dopamine electrostatic interaction. The size of the DNA toroids could be modulated by varying the concentration of dopamine. This study offers useful information about the DNA condensation induced by monovalent cations and the sample preparation for AFM measurement and application.

One-Step Synthesis of Folic Acid Protected Gold Nanoparticles and Their Receptor-Mediated Intracellular Uptake

We report here a facile method to obtain folic acid (FA)-protected gold nanoparticles (Au NPs) by heating an aqueous solution of HAuCl4/FA in which FA acts as both the reducing and stabilizing agent. The successful formation of FA-protected Au NPs is demonstrated by UV/Vis spectroscopy, transmission electron microscopy (TEM), selected-area electron diffraction (SAED), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FTIR). ne intracellular uptake of these nanoparticles is facilitated by HeLa cells overexpressing the folate reporter, which itself is significantly inhibited by free FA in a competitive assay as quantified by inductively coupled plasma mass spectroscopy (ICP-MS). This simple one-step approach affords a new perspective for creating functional nanomaterials, and the resulting biocompatible, functional Au NPs may find some prospective applications in various biomedical fields.

The adsorption of dopamine on gold and its interactions with iron(III) ions studied by microcantilevers

The adsorption of dopamine (DA) molecules on gold and their interactions with Fe3+ were studied by a microcantilever in a flow cell. The microcantilever bent toward the Au side with the adsorption of DA due to the change Of Surface stress induced by the intermolecular hydrogen bonds of DA or the charge transfer effect between adsorbates and the Substrate. The interaction process between DA adsorbates and Fe3+ was revealed by the deflection curves of microcantilever. As indicated by the appearance of a variation during the decline of curves, two steps were observed in the curve at relative high concentrations of Fe3+. In this case, Fe3+ reacted with DA molecules only in the outer layers and the complexes removed with solution. Then Fe3+ reacted further with DA molecules forming the surface complex in the first layer next to the gold. At this stage, the stability Of Surface complexes was time dependent, i.e., unstable initially and stable finally. This may be due to the surface complexes change from mono-dentate to bi-dentate complexes. In another case, i.e., at relative low concentration of Fe3+, only the first step was observed as indicated by the absence of a variation.

Folate-Conjugated Micelles and Their Folate-Receptor-Mediated Endocytosis

A folate-conjugated copolymer PEG-PLA-PLL/folate was synthesized and mixed with pure PEG-PLA-PLL and a fluorescent model drug mFITC to prepare folate-conjugated micelles. The distribution of micelles was studied on cancer-cell-bearing mice via frozen slicing. The results show that mFITC is successfully encapsulated into folate(+) and folate(-)micelles; PEG-PLA-PLL micelles the latter can be internalized by both HeLa and CHO cells without selectivity due to their cationic surface charges, while folate(+)micelles exhibit more preferential endocytosis by HeLa cells than by CHO cells. The folate(-)micelles showed retention in both organs and tumors. The folate(+)micelles are a promising active targeting drug delivery system for FR over-expressing cells and they accumulate in tumor beds.

Effect of buffer capacity on electrochemical behavior of dopamine and ascorbic acid

It is well known that the electrochemical oxidation of dopamine and ascorbic acid includes the proton and electron transfers at a glassy carbon electrode and their redox potentials are dependent on the pH of solution. When the concentration of the buffer is not enough to neutralize the protons produced by electrochemical oxidation of dopamine and ascorbic acid, two peaks of them can be observed in cyclic voltammograms. The height of the new peak is in proportion to the concentration of proton acceptor including HPO42-, 2,4,6-trimethylpyridine, tris (hydroxymethyl) aminomethane. Moreover, the potential of it is dependent on the type and the concentration of buffer at the same pH of bulk solution. However, this phenomenon cannot be attributed to the interaction between proton acceptor and dopamine or ascorbic acid. So, we think the phenomenon is caused by the acute change of pH at the surface of working electrode. Similar results were also observed in the rotating disk voltammograms. It can be concluded that the electrochemical behavior of some compounds is dependent on the concentration of buffer when this concentration is not enough to neutralize the protons produced in electrochemical oxidation.

Simultaneous determination of dopamine and ascorbic acid at an in-site functionalized self-assembled monolayer on gold electrode

The in-site functionalization of 4-aminothiophenol (4-ATP) self-assembled monolayer on gold electrode at physiological pH yields a redox active monolayer of 4'-mercapto-N-phenylquinone diimine (MNPD). The functionalized electrode exhibits excellent electrocatalytic responses towards dopamine (DA) and ascorbic acid (AA), reducing the overpotentials by about 0.22 V and 0.34 V, respectively, with greatly enhanced current responses. Due to its different catalytic activities toward DA and AA, the modified electrode resolves the overlapping voltammetric responses of DA and AA into two well-defined voltammetric peaks by differential pulse voltammetry (DPV), which can be used for the simultaneous determination of these species in a mixture. The catalytic peak current obtained from DPV was linearly related to DA and AA concentration in the ranges of 5.0 x 10-6 - 1.25 x 10-4 M and 8.0 x 10-6 - 1.3 x 10-4 M with correlation coefficient of 0.999 and 0.998, respectively. The detective limits (3sigma) for DA and AA were found to be 1.2 x 10-6 M and 2.4 x 10-6 M, respectively.

Effects of a surfactant on the electrocatalytic activity of cobalt hexacyanoferrate modified glassy carbon electrode towards the oxidation of dopamine

The cobalt hexacyanoferrate film (CoHCF) was deposited on the surface of a glassy carbon (GC) electrode with a potential cycling procedure in the presence and absence of the cationic surfactant, cetyl trimethylammonium bromide (CTAB), to form CoHCF modified GC (CoHCF/GC) electrode. It was found that CTAB would affect the growth of the CoHCF film, the electrochemical behavior of the CoHCF film and the electrocatalytic activity of the CoHCF/GC electrode towards the electrochemical oxidation of dopamine (DA). The reasons of the electrochemical behavior of CoHCF/GC electrode influenced by CTAB were investigated using FTIR and scanning electron microscope (SEM) techniques. The apparent rate constant of electrocatalytic oxidation of DA catalyzed by CoHCF was determined using the rotating disk electrode measurements.