催产素在脊髓水平对电针镇痛的影响

采用玻璃微电极胞外记录和脊髓表面给药的方法观察了催产素（ＯＴ）、抗催产素血清（ＡＯＴＳ）以及电针穴位对背角神经元伤害性诱发放电的影响。结果表明：电针穴位或脊髓表面施加ＯＴ可部分抑制脊髓背角神经元的伤害性诱发放电;在电针的基础上施加ＯＴ则明显加强电针的抑制效应;相反,用ＡＯＴＳ预处理后,电针的抑制作用放取消。提示ＯＴ在脊髓水平参与了对痛觉信息的调制,并与一定频率的针刺镇痛有关。     

In vivo and in vitro studies on the appearance of LHRH neurons in the hypothalamus of perinatal rats

Summary Ontogenetic development of LHRH-containing neurons was studied by fluorescence and enzyme immunohistochemistry in rats. In in vitro studies, the tissues of the septal-chiasmatic and mediobasal hypothalamic areas of fetal rats on day 16.5 or 18.5 of gestation were trypsinized separately for dissociation of the neural cells, and cultured for several days. Immunopositive reaction against LHRH was first detected in nerve cells derived from both areas of the hypothalamus of the fetuses on days 16.5 and 18.5 of gestation, after 8 and 6 days culture, respectively. The cells were small, and seemed to be bipolar in morphology indicating an axon and arborized dendrites. Immunopositive material occurred in the cell soma as well as in the cellular processes. In in vivo studies, immunopositive material, possibly deposited in nerve fibers, appeared first in OVLT and simultaneously in the external layer of the median eminence of fetuses on day 20.5 of gestation. The immunoreactive fibers increased in number in both parts with development, especially after birth in the median eminence. No immunopositive material was detected within any neural cell bodies nor in the cytoplasm of any ependymal cells.This work was financed by the Ministry of Education, Japan. No. 257008. We would like to thank Dr. Katsuhiko Saito (Department of Surgery, Tokushima University) for his kind advice on the preparation of the antibody used for the immunofluorescence study.     

17β‐Oestradiol facilitates M2 macrophage skewing and ameliorates arrhythmias in ovariectomized female infarcted rats

Epidemiological studies have suggested a lower incidence of arrhythmia‐induced sudden cardiac death in women than in men. 17β‐oestradiol (E2) has been reported to have a post‐myocardial infarction antiarrhythmic effect, although the mechanisms have yet to be elucidated. We investigated whether E2‐mediated antioxidation regulates macrophage polarization and affects cardiac sympathetic reinnervation in rats after MI. Ovariectomized Wistar rats were randomly assigned to placebo pellets, E2 treatment, or E2 treatment +3‐morpholinosydnonimine (a peroxynitrite generator) and followed for 4 weeks. The infarct sizes were similar among the infarcted groups. At Day 3 after infarction, post‐infarction was associated with increased superoxide levels, which were inhibited by administering E2. E2 significantly increased myocardial IL‐10 levels and the percentage of regulatory M2 macrophages compared with the ovariectomized infarcted alone group as assessed by immunohistochemical staining, Western blot and RT‐PCR. Nerve growth factor colocalized with both M1 and M2 macrophages at the magnitude significantly higher in M1 compared with M2. At Day 28 after infarction, E2 was associated with attenuated myocardial norepinephrine levels and sympathetic hyperinnervation. These effects of E2 were functionally translated in inhibiting fatal arrhythmias. The beneficial effect of E2 on macrophage polarization and sympathetic hyperinnervation was abolished by 3‐morpholinosydnonimine. Our results indicated that E2 polarized macrophages into the M2 phenotype by inhibiting the superoxide pathway, leading to attenuated nerve growth factor‐induced sympathetic hyperinnervation after myocardial infarction.     

PTSD促进大鼠中缝背核细胞色素c表达

目的研究创伤后应激障碍(PTSD)大鼠中缝背核神经元细胞色素C(Cyt-c)的表达变化。方法应用无连续单一刺激(SPS)方法建立PTSD大鼠模型,随机分为SPS刺激后1d、4d、7d和对照组,应用酶组织化学法和RT-PCR方法观察中缝背核神经元Cyt-c的表达变化。结果光镜酶细胞化学法和RT-PCR法显示中缝背核神经元Cyt-c染色阳性细胞于SPS刺激后1d明显高于对照组,4d逐渐增高,并于7d达到高峰。电镜下显示Cyt-c阳性反应产物主要分布在中缝背核神经元线粒体膜,SPS刺激后可见Cyt-c释放到胞浆中。结论 SPS刺激引起Cyt-c在PTSD大鼠中缝背核神经元呈过表达。     

The Kv2.1 channels mediate neuronal apoptosis induced by excitotoxicity

Chronic loss of intracellular K⁺ can induce neuronal apoptosis in pathological conditions. However, the mechanism by which the K⁺ channels are regulated in this process remains largely unknown. Here, we report that the increased membrane expression of Kv2.1 proteins in cortical neurons deprived of serum, a condition known to induce K⁺ loss, promotes neuronal apoptosis. The increase in I _K current density and apoptosis in the neurons deprived of serum were inhibited by a dominant negative form of Kv2.1 and MK801, an antagonist to NMDA receptors. The membrane level of Kv2.1 and its interaction with SNAP25 were increased, whereas the Kv2.1 phosphorylation was inhibited in the neurons deprived of serum. Botulinum neurotoxin, an agent known to prevent formation of soluble N -ethylmaleimide-sensitive factor attachment protein receptor complex, suppressed the increase in I _K current density. Together, these results suggest that NMDA receptor-dependent Kv2.1 membrane translocation is regulated by a soluble N -ethylmaleimide-sensitive factor attachment protein receptor-dependent vesicular trafficking mechanism and is responsible for neuronal cell death induced by chronic loss of K⁺.     

Persistent tetrodotoxin-resistant Na+ currents are activated by prostaglandin E2 via cyclic AMP-dependent pathway in C-type nodose neurons of adult rats

It has been documented that nodose neurons express TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) Na(+) channels. However, wheteher nodose neurons functionally express persistent TTX-R Na(+) currents has not been reported. The present study first demonstrated persistent TTX-R Na(+) channel activities in 7/19 C-type nodose neurons in the presence of PGE(2) using whole-cell patch. Voltage-dependent property showed that persistent TTX-R Na(+) currents were activated at near -60mV and channels were maintained open. The average peak was approximately 300-500pA. The mid-point of activation exhibited a greater shift to a more hyperpolarized potential in the neurons co-expressing TTX-R and persistent TTX-R Na(+) currents than those expressing TTX-R only. This effect of PGE(2) was also mimicked by Forskolin. The fact that persistent TTX-R Na(+) currents were only activated by PGE(2) suggested that the modulatory effects of PGE(2) on persistent TTX-R Na(+) currents are crucial in PGE(2)-mediated neuronal excitability, and may have a great impact on specifically physiological significance.     

猫皮层体感Ⅱ区内脏伤害感受神经元的电生理特性及形态特征

应用胞内记录和标记技术,观察了猫皮质第Ⅱ感觉区内脏大神经代表区的神经元对电刺激内脏大神经反应诱发反应及形态特征。结果表明,在２５１个记录单位中,有１０９个为内脏伤害性感受神经元,其诱发反应分为兴奋性、抑制性及混合性三类。在形式上ＩＳＰＳ及ＥＰＳＰ－ＩＰＳＰ序列反应较多。对其中２１个神经元用神经生物素进行细胞内电泳标记,显示细胞的形态特点是胞体较小,分布于皮质Ⅱ、Ⅲ、Ⅴ层,其中兴奋性和神经元形态多为     

Developmental Deformity Due to scalloped Non‐Function in Drosophila Brain Leads to Cognitive Impairment

Neural identity and wiring specificity are fundamental to brain function. Factors affecting proliferation of the progenitor cells leading to an expansion or regression of specific neuronal clusters are expected to challenge the process of formation of precise synaptic connections with their partners and their further integration to result in proper functional neural circuitry. We have investigated the role of scalloped, a Hippo pathway gene in Drosophila brain development and have shown that its function is critical to regulate proliferation of Mushroom Body Neuroblasts and to limit the neuronal cluster size to normal in the fly brain. Here we investigate the consequent effect of the anatomical phenotype of mutant flies on the brain function, as exemplified by their cognitive performance. We demonstrate that the neural expansion in important neural clusters of the olfactory pathway, caused due to Scalloped inactivation, imparts severe disabilities in learning, short‐term memory and long‐term memory. Scalloped knockdown in αβ Kenyon Cell clusters drastically reduces long‐term memory performance. Scalloped deficiency induced neural expansion in antennal lobe and ellipsoid body neurons bring down short‐term memory performance significantly. We also demonstrate that the cognitive impairments observed here are not due to a problem in memory formation or execution in the adult, but are due to the developmental deformities caused in the respective class of neurons. Our results strongly indicate that the additional neurons generated by Scalloped inactivation are not synergistically integrated into, but rather perturb the formation of precise functional circuitry.     

5—羟色胺抑制谷氨酸对海马神经元的毒性作用

为探讨5-羟色胺（5-HT）对过量谷氨酸（glutamate,Glu)神经毒性的影响。观察了5-HT存在时,过量Glu对海马细胞存活率、海马脑片CA1区群锋电位（population spike,PS)及神经细胞膜Ga^2 电流的影响。结果发现：5-HT可明显提高过量Glu作用下海马神经细胞的存活率,减缓Glu对海马脑片CA1区PS的降低作用;在细胞膜上,5-HT可明显减弱Glu诱导的Ca^2 内向电流,推测,一定浓度的5-HT具有抑制过量Glu神经毒性的作用。在细胞膜上5-HT可明显减弱Glu诱导的Ca^2 内向电流,推测,一定浓度的5-HT具有抑制过量Glu神经毒性的作用,其机制可能在于5-HT与细胞膜上特定的受体结合,抑制了Glu诱导的Ca^2 内流。