“The King is dead”: Checkmating ion channels with tethered toxins

The quickest possible checkmate in the game of chess requires two moves using a pawn and the queen. Metaphorically speaking, the pawn (a membrane tether) and the queen (a toxin) work together to checkmate an ion channel within a neuronal circuit. This strategy termed “tethered toxin” (t-toxin) is based on the use of genetically encoded peptide toxins that are anchored to the cell-membrane via a glycolipid or transmembrane tether. Because of their mode of action at the cell surface, t-toxins act only on ion channels and receptors of the cell that is expressing the t-toxin, and not on identical receptors present in neighboring cells that do not express the t-toxin. In this mini-review we discuss the design of these genetic tools and their application for cell-specific and temporal manipulation of ion channel-mediated activities in vivo.     

Corticotropin releasing factor antagonist reduces ischemic hippocampal neuronal injury

This experiment tested the hypothesis that corticotropin-releasing factor (CRF) contributes to hippocampal ischemic injury. The antagonist to CRF (alpha-CRF) was administered intraventricularly 15 min prior to 10 min of transient forebrain ischemia in the Wistar rat. alpha-CRF demonstrated a neuroprotective effect in a dose-dependent manner most notable in CA1. There was also an increase in postischemic EEG recovery. It is postulated that CRF contributes to hippocampal ischemic injury through increased neuronal activity.     

饮用醋酸铅对大鼠神经元棘密度及酶活性的影响

目的：探索铅对幼鼠中枢神经的影响。方法：在大鼠仔鼠饮用醋酸铅（Ｐｂ２＋３０ｍｇ·Ｌ－１）水溶液３个月后，应用Ｇｏｌｇｉ镀银法观察大脑皮质区锥体细胞树突小棘并作酶组织化学图象分析。结果：染毒组基树突与侧树突的棘密度均明显低于正常对照组（Ｐ＜０．０１），染毒组ＡＴＰ酶积分吸光度（ＩＯＤ）明显低于正常对照组（Ｐ＜０．０１），磷酯酶的ＩＯＤ明显高于对照组（Ｐ＜０．０１）。结论：实验表明醋酸铅对仔鼠大脑神经元树突、细胞膜及能量代谢有明显的毒作用     

Firing Inhibition Processes in the Response Dynamics of Isolated Crayfish Nerve Cell to the Photodynamic Effect of Sulphonated Aluminium Phthalocyanine: Participation of Free Radicals and Ca2+

. Chemical modifications allows the enhancement or attenuation of the cell response to photodynamic effect and provides information on the mechanisms of this effect. Isolated crayfish neurons were incubated for 30 min with 10⁻⁷ M Photosens (AlPcS _n ) and irradiated by He-Ne laser (632.8 nm, 0.3 W/cm²). Such treatment caused firing inhibition until it was irreversibly abolished. The antioxidants homocarnosine, DABCO or ascorbate, pro-oxidant, FeSO₄ or a mixture of FeSO₄ and ascorbate; Ca²⁺ modulators, CdCl₂, verapamil, EDTA, dantrolene, caffeine, theophylline, or a threefold CaCl₂ concentration were used to modify neuron response (firing inhibition and abolition). Homocarnosine, CdCl₂, DABCO, dantrolene, and caffeine or theophylline added 30–90 min before irradiation, increased neuron lifetime under the photodynamic effect of Photosens whereas FeSO₄/ascorbate, EDTA, threefold Ca²⁺ concentration or caffeine (added 5 min before irradiation) decreased neuron lifetime. It is concluded that, free radical processes and Ca²⁺ participate in the Photosens-induced photodynamic inhibition and subsequent irreversible abolition of neuron firing. Paper received 28 April 1999;accepted after revision 4 October 1999.     

七氟烷通过ERK1／2／Nrf2信号通路诱导HO-1基因表达抑制神经元凋亡

目的：研究七氟烷（Sevoflurane）诱导神经元血红素氧合酶－1（HO－1）基因表达的信号转导通路，探讨七氟烷脑保护机制。 方法：将培养7d的新生Wistar大鼠海马神元随机分为5组：正常培养组（C组）、氧糖剥夺组（D组）、2％七氟烷＋氧糖剥压组（S1组）、4％七氟烷＋氧糖剥压组（S2组）、4％七氟烷＋U-012＋4％七氟烷＋氧糖剥压组（U组）。C组和S2组神经元分别给予2％或4％七氟烷预处理60min后同D组处理。U组在神经元给予4％七氟烷处理同时在培养液中加入U－0126使其终浓度为10μmol/L后同S2组处理。收集神经元进行HO－1－mRNA和ERK1/2、Nrf2、AP-1和HO－1蛋白表达的检测，检测神经元的存活率和凋亡率。 结果：与C组比较，D组神经无HO－1蛋白表达增加（P〈0.05）,ERK1/2,Nrf2和AP-1蛋白表达增加（P〈0.05），神经元存活率降低、凋亡率增加（P〈0.01）.与D组比较，S1组神经元HO－1－mRNA和HO-1蛋白表达增加（P〈0.01）,ERK1/2和Nrf2蛋白表达增加（P〈0.01）,AP－1蛋白表达变化不明显（P〉0.05），经元存活率长高、凋亡率降低（P〈0.01）.与S2组比较，U组神经元HO-1－mRNA和HO－1蛋白表达降低（P〈0.01）,ERK1/2和Nrf2蛋白表达降低（P〈0.01），AP-1蛋白表达表达变化不明显（P〉0.05）,神经元存活率降低、凋亡率增加（P〈0.01）. 结论：Sevoflurane通过ERK1/2/Nrf2信号通路诱导神经元HO-1-mRNA表达，抑制氧糖剥夺神经元的凋亡。     

The maturation-dependent change in fibronectin receptor density of mouse dorsal root ganglion neurons

The maturation-dependent change in fibronectin receptor density of mouse dorsal root ganglion neurons were investigated by an immuno-cytofluorometric method. The receptor density showed a drastic decrease around birth and a smaller change after birth.     

衰老时人大脑皮质超微结构的变化

用电子显微镜对10例正常老年人大脑额叶、顶叶和颞叶皮质进行了研究。发现神经元核内出现包含物,神经细胞和胶质细胞质内出现多形态的纤维性包含物,线粒体变性,胞质空泡化以及脂褐素体的沉积等。突触的变性发现为突触前、后末梢内线粒体变性,突触小泡的融合破坏。     

Localization of insulin-like growth factor I (IGF-I)-like immunoreactivity in the developing and adult rat brain

The cellular distribution of insulin-like growth factor I (IGF-I) immunoreactivity was examined in the rat brain from embryonic day 15 to maturity. IGF-I immunoreactivity was found in the perikarya of neurons distributed along the entire extension of the neuronal tube in all the embryonic ages studied (E15, E17, E19 and E21). In E21 animals, the majority of immunoreactive neurons was located in the olfactory bulb, cerebral cortex, hippocampus, striatum, diencephalon, mesencephalic colliculi, trigeminal ganglion and in motoneurons of the brainstem. In 10- and 20-day-old rats, in addition to the above areas, IGF-I immunoreactivity was also observed in capillary walls, ependymal cells, choroid plexus, glial cells and most fiber paths. In postnatal ages, immunoreactivity in neuronal somas mainly restricted to the cell nuclei. However, IGF-I immunoreactivity in the neuron cytoplasm was observed in 20-day-old rats treated with colchicine while fiber paths and neuronal cell nuclei were negative in these animals. In the telencephalon of 20-day-old rats injected with colchicine, the most intense immunoreactive neurons were observed in the olfactory bulb, cerebral cortex, tenia tecta, hippocampus, islands of Calleja, septal nuclei, striatum, endopyriform nucleus and amygdala. Most diencephalic nuclei, the substantia nigra, the mesencephalic colliculi, Purkinje cells in the cerebellar cortex and several nuclei in mesencephalon, pons and medulla oblongata were also immunoreactive. In adult rats injected with colchicine, IGF-I immunoreactivity was located in the same areas as in 20-day-old rats. The number of immunoreactive cells and the intensity of the staining was reduced in adult rats as compared to that found in young postnatal animals. Glial cells were negative in adults. The distribution of IGF-I in the developing and mature rat brain supports the proposed roles of this peptide as a neuromodulator and neurotrophic factor.     

银杏叶提取物对缺血-再灌流神经元损伤的保护作用及其信号转导机制

目的研究银杏叶提取物(EGB761)对缺糖缺氧/复糖复氧神经元损伤的保护作用,并探讨其主要细胞内信号转导机制。方法利用原代培养的皮层神经元,通过去除培养液中的糖和氧(oxygen and glucose deprivation,OGD)模拟缺血缺氧,恢复糖氧供给模拟再灌流。通过免疫蛋白印迹法测定Akt、磷酸化Akt(p-Akt)蛋白的表达。再灌流时加用银杏叶提取物(EGB761)观察其对神经元保护作用以及对Akt、p-Akt表达的调节作用。结果缺糖缺氧/复糖复氧后神经元p-Akt表达明显下降,EGB761可剂量依赖地保护神经元活性,并可上调因缺糖缺氧/复糖复氧而降低的p- Akt蛋白的表达,但该作用不被Ly294002所阻断。结论EGB761对培养的神经元缺糖缺氧/复糖复氧损伤有保护作用,该作用可能与非PI3K依赖的p-Akt信号转导通路激活有关。     

当归芍药散改良方对体外培养海马神经元的作用

目的探索当归芍药散改良方（ｍＤＳＳ）改善老年性痴呆鼠空间学习记忆能力的机制。方法采用体外培养的海马神经元作为模型，加入服用ｍＤＳＳ的痴呆鼠血清，观察其对神经元形态学变化的影响。结果ｍＤＳＳ可延长海马神经元的存活时间，提高存活神经元中有突起神经元所占比率，对胞体的大小没有明显影响。结论ｍＤＳＳ改善学习记忆可能与其促进海马神经元存活及突起生长有关。