• 【雌性大鼠母体行为期间表达Fos的纹状体终末神经元的内侧视前区和腹床核的投影位点。】 复制标题 收藏 收藏
    DOI:10.1046/j.1365-2826.1997.t01-1-00597.x 复制DOI
    作者列表:Numan M,Numan MJ
    BACKGROUND & AIMS: :Medial preoptic area (MPOA) and ventral bed nucleus of the stria terminalis (VBST) neurons are involved in maternal behavior, but the neural sites to which the maternally relevant neurons project have not been determined. Since MPOA and VBST neurons express Fos during maternal behavior, we used a double-labeling immunocytochemical procedure to detect both Fos and a retrograde tracer, wheat germ agglutinin (WGA), in order to determine where these Fos neurons project. On Day 4 postpartum, fully maternal females were separated from their litters. On Day 5, WGA was iontophoretically injected into one of the following regions known to receive MPOA and/or VBST input: Lateral septum, medial hypothalamus at the level of the ventromedial nucleus, lateral habenula, ventral tegmental area, retrorubral field, or periaqueductal gray. On Day 7, females received a 2-h test with either pups or candy, after which they were perfused and their brains were processed for the detection of Fos and WGA. As expected, females tested with pups had more Fos-containing neurons in the MPOA and VBST than did females tested with candy. After WGA injections into several brain sites, the number of double-labeled cells observed in the MPOA and VBST was greater for the maternal females when compared to the non-maternal females. Therefore, these results pinpointed neural circuits that were activated during maternal behavior. For the maternal females, Fos-containing neurons in the MPOA projected most strongly to the medial hypothalamus at the level of the ventromedial nucleus and to the lateral septum, while Fos-containing neurons in the VBST projected most strongly to the retrorubral field, ventral tegmental area, and medial hypothalamus. Although relatively few MPOA and VBST neurons which expressed Fos during maternal behavior projected to the periaqueductal gray, these Fos-expressing neurons made up a relatively large proportion of the MPOA and VBST projection to the periaqueductal gray. This study suggests that MPOA and VBST efferents project to a variety of regions to promote full maternal responsiveness.
    背景与目标: : 视前区 (MPOA) 和纹状体 (VBST) 神经元的腹床核参与母体行为,但尚未确定与母系相关的神经元投射到的神经部位。由于MPOA和VBST神经元在母体行为中表达Fos,因此我们使用双标记免疫细胞化学程序来检测Fos和逆行示踪剂小麦胚芽凝集素 (WGA),以确定这些Fos神经元的投射位置。产后第4天,将完全的产妇与产仔分开。在第5天,将WGA离子电渗注射到以下已知接受MPOA和/或VBST输入的区域之一: 外侧隔膜,腹内侧核水平的下丘脑内侧,外侧habenula,腹侧被盖区,脑后野,或导水管周围灰色。在第7天,雌性接受了2小时的幼崽或糖果测试,然后对其进行灌注,并对其大脑进行处理以检测Fos和WGA。正如预期的那样,与用糖果测试的雌性相比,用幼崽测试的雌性在MPOA和VBST中具有更多的含Fos的神经元。在将WGA注射到多个大脑部位后,与非母体女性相比,在MPOA和VBST中观察到的双标记细胞数量更多。因此,这些结果确定了在母体行为期间激活的神经回路。对于母体女性,MPOA中含Fos的神经元最强烈地投射到腹内侧核水平的下丘脑内侧和外侧隔,而VBST中含Fos的神经元最强烈地投射到脑后野,腹侧被盖区和下丘脑内侧。尽管在投射到导水管周围灰色的母体行为中表达Fos的MPOA和VBST神经元相对较少,但这些表达Fos的神经元在MPOA和VBST投射到导水管周围灰色的比例相对较大。这项研究表明,MPOA和VBST传出剂投射到各个地区,以促进孕产妇的全面反应。
  • 【大鼠中中核神经元对结肠直肠扩张的反应特征。】 复制标题 收藏 收藏
    DOI:10.1016/s0168-0102(97)01177-2 复制DOI
    作者列表:Kawakita K,Sumiya E,Murase K,Okada K
    BACKGROUND & AIMS: :The effects of colorectal distension (CRD) were examined on neurons located in and around the nucleus submedius (Sm) in the medial thalamus of urethane-anesthetized rats. A total of 66 units (49 in the Sm and 17 in immediately surrounding regions) responding to cutaneous pinch were tested to examine their responsiveness to the CRD. All the neurons that responded to cutaneous stimulation were nociceptive specific (NS) neurons. Based on their responses to the CRD the Sm neurons were classified into three types as follows: 23 (47%) of 49 neurons in the Sm and three (18%) of 17 neurons near the Sm had tonic excitatory responses with long-lasting after-discharges (type I); nine (18%) Sm neurons and four (24%) peri-Sm neurons were tonically excited but had no after-discharge (type II); and seven (14%) Sm neurons were inhibited (type III). Ten (20%) Sm neurons and 10 (59%) peri-Sm neurons did not respond to CRD. All the excitatory and inhibitory responses to CRD increased with increasing CRD pressure. Simultaneous application of CRD and cutaneous pinch did not produce a reduced response (nocigenic inhibition). These results demonstrate that most of the Sm neurons receive convergent viscerosomatic inputs from the colon and/or rectum and from the skin, suggesting that the Sm may participate in visceral nociception.
    背景与目标: : 检查了大肠扩张 (CRD) 对氨基甲酸乙酯麻醉大鼠内侧丘脑中中核 (Sm) 及其周围神经元的影响。测试了对皮肤挤压有反应的总共66个单位 (Sm中有49个,周围区域中有17个),以检查它们对CRD的反应能力。所有对皮肤刺激有反应的神经元都是伤害性特异性 (NS) 神经元。根据对CRD的反应,Sm神经元分为三种类型: Sm中49个神经元中的23个 (47% 个) 和Sm附近的17个神经元中的3个 (18% 个) 具有强直兴奋反应,放电后持续时间长 (I型); 九个 (18%) Sm神经元和四个 (24%) 周围Sm神经元被音调兴奋,但没有放电后 (II型); 七个 (14%) Sm神经元被抑制 (III型)。10个 (20%) Sm神经元和10个 (59%) 周围Sm神经元对CRD没有反应。随着CRD压力的增加,对CRD的所有兴奋和抑制反应均增加。同时应用CRD和皮肤捏合不会产生降低的反应 (抑制)。这些结果表明,大多数Sm神经元从结肠和/或直肠以及皮肤接收会聚的内脏体输入,表明Sm可能参与内脏伤害感受。
  • 【靶向Toll-IL-1R域的诱饵肽抑制LPS和TLR4-active代谢物吗啡-3葡萄糖醛酸苷对感觉神经元的敏化。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-017-03447-9 复制DOI
    作者列表:Allette YM,Kim Y,Randolph AL,Smith JA,Ripsch MS,White FA
    BACKGROUND & AIMS: :Accumulating evidence indicates that Toll-like receptor (TLR) signaling adapter protein interactions with Toll/Interleukin-1 Receptor (TIR) domains present in sensory neurons may modulate neuropathic pain states. Following ligand interaction with TLRs, TIR serves to both initiate intracellular signaling and facilitate recruitment of signaling adapter proteins to the intracytoplasmic domain. Although TLR TIR is central to a number of TLR signaling cascades, its role in sensory neurons is poorly understood. In this study we investigated the degree to which TLR TIR decoy peptide modified to include a TAT sequence (Trans-Activator of Transcription gene in HIV; TAT-4BB) affected LPS-induced intracellular calcium flux and excitation in sensory neurons, and behavioral changes due to TLR4 active metabolite, morphine-3-glucuronide (M3G) exposure in vivo. TAT-4BB inhibited LPS-induced calcium changes in a majority of sensory neurons and decreased LPS-dependent neuronal excitability in small diameter neurons. Acute systemic administration of the TAT-4BB reversed M3G-induced tactile allodynia in a dose-dependent manner but did not affect motor activity, anxiety or responses to noxious thermal stimulus. These data suggest that targeting TLR TIR domains may provide novel pharmacological targets to reduce or reverse TLR4-dependent pain behavior in the rodent.
    背景与目标: : 越来越多的证据表明,Toll样受体 (TLR) 信号衔接蛋白与感觉神经元中存在的Toll/Interleukin-1受体 (TIR) 结构域的相互作用可能调节神经性疼痛状态。配体与tlr相互作用后,TIR既可启动细胞内信号传导,又可促进信号衔接蛋白向胞浆内结构域的募集。尽管TLR TIR是许多TLR信号级联的核心,但对其在感觉神经元中的作用知之甚少。在这项研究中,我们调查了修饰为包含TAT序列 (HIV中转录基因的反式激活因子; TAT-4BB) 的TLR TIR诱饵肽对LPS诱导的细胞内钙通量和感觉神经元的兴奋以及由于TLR4活性代谢物引起的行为变化的影响程度,morphine-3-glucuronide (M3G) 体内暴露。TAT-4BB抑制了大多数感觉神经元中LPS诱导的钙变化,并降低了小直径神经元中LPS依赖性神经元的兴奋性。TAT-4BB的急性全身给药以剂量依赖性方式逆转了M3G-induced的触觉异常性疼痛,但不影响运动活动,焦虑或对有害热刺激的反应。这些数据表明,靶向TLR TIR结构域可以提供新的药理学靶标,以减少或逆转啮齿动物的TLR4-dependent疼痛行为。
  • 【大鼠下丘脑外侧,可卡因和苯丙胺调节的转录本 (CART) 神经元向背侧中缝和/或蓝斑的投射模式。】 复制标题 收藏 收藏
    DOI:10.1016/j.brainres.2012.11.042 复制DOI
    作者列表:Yoon YS,Lee HS
    BACKGROUND & AIMS: :The present study was designed to reveal the projection patterns of lateral hypothalamic (LH), cocaine- and amphetamine-regulated transcript (CART) neurons to the dorsal raphe (DR) and/or the locus coeruleus (LC) in the rat. After the injection of Red or Green Retrobeads into the DR or LC, LH sections were immunostained for CART and/or melanin-concentrating hormone (MCH). First, CART-immunoreactive axon terminals formed close appositions to the DR (or LC) neuronal profiles. Second, a subpopulation of CART neurons containing MCH projected to the monoaminergic nuclei; the majority of labeled neurons were observed in the dorsal hypothalamic area, the dorsal part of the posterior hypothalamic area, and the zona incerta. Cells were also observed in the perifornical part of the LH, the dorsomedial hypothalamic nucleus, the peduncular and the magnocellular parts of the LH. Of the total population of DR (or LC)-projecting cells, CART/MCH co-containing neurons were 9.5% ± 1.6% (or 10.8% ± 1.3% for LC). Finally, a subset of CART (or MCH) neurons provided divergent axon collaterals to the DR and the LC. Of the entire CART (or MCH) cell population, 3.9% ± 0.8% (or 5.6% ± 1.0% for MCH) sent axon collaterals to the DR/LC. CART/MCH co-containing neurons projecting to the DR or LC might be involved in the feeding-related regulation of arousal, stress-related responses, and emotional behaviors. Thus, CART (or MCH) cells that send divergent axon collaterals to the DR/LC might have a simultaneous (and possibly more efficient) way to exert their specific influences on the aminergic nuclei.
    背景与目标: : 本研究旨在揭示下丘脑外侧 (LH),可卡因和苯丙胺调节的转录本 (CART) 神经元向大鼠背侧中缝 (DR) 和/或蓝斑 (LC) 的投射模式。将红色或绿色的回珠注射到DR或LC中后,对LH切片进行了CART和/或黑色素浓缩激素 (MCH) 的免疫染色。首先,CART免疫反应性轴突末端与DR (或LC) 神经元谱形成紧密结合。其次,包含MCH的CART神经元亚群投射到单胺能核; 在下丘脑背侧区域,下丘脑后区域的背侧部分和透明带中观察到大多数标记的神经元。在LH的穹顶周围部分,下丘脑背核,LH的足部和大细胞部分也观察到细胞。在DR (或LC) 投射细胞的总数中,CART/MCH共含神经元为9.5% ± 1.6% (LC为10.8% ± 1.3%)。最后,CART (或MCH) 神经元的子集为DR和LC提供了不同的轴突侧支。在整个CART (或MCH) 细胞群中,3.9% ± 0.8% (或5.6% ± 1.0% MCH) 向DR/LC发送轴突侧支。向DR或LC投射的CART/MCH共含神经元可能参与了与喂养相关的唤醒调节,压力相关的反应和情绪行为。因此,向DR/LC发送不同轴突侧支的CART (或MCH) 细胞可能具有同时 (甚至可能更有效) 对氨基能核施加特定影响的方式。
  • 【培养的人神经元中蛋白质丝氨酸/苏氨酸磷酸酶抑制剂选择性破坏稳定的微管和轴突。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Merrick SE,Trojanowski JQ,Lee VM
    BACKGROUND & AIMS: Paired helical filaments (PHFs) in the neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) brains are composed of highly phosphorylated isoforms of tau (PHFtau) that fail to bind microtubules (MTs), and the levels of MT-binding competent tau are decreased in AD brains with abundant PHFtau. Because this loss of MT binding could compromise the viability of tangle-bearing AD neurons by destabilizing MTs, we asked whether these events could be initiated by inhibiting protein phosphatase 1 (PP1) and PP2A in cultured human neurons (NT2N cells) using okadaic acid (OK) and calyculin-A (CL-A). The treatment of NT2N cells with OK and CL-A increased tau phosphorylation, decreased the binding of tau to MTs, and selectively depolymerized the more stable detyrosinated MTs but not the more labile tyrosinated MTs. Significantly, this led to the rapid degeneration of axons, which are enriched in the more stable detyrosinated MTs, and PP2A was implicated in the initiation of this cascade of events because PP2A but not PP1 was closely associated with MTs in the NT2N cells. These studies imply that inactivation of PP2A in vulnerable neurons of the AD brain may play a mechanistic role in the conversion of normal tau into PHFtau, in the depolymerization of stable MTs, and in the degeneration of axons emanating from tangle-bearing neurons.

    背景与目标: 阿尔茨海默氏病 (AD) 大脑的神经原纤维缠结 (nft) 中的成对螺旋细丝 (phf) 由高度磷酸化的tau亚型 (PHFtau) 组成,无法结合微管 (MTs),并且MT结合的水平在具有丰富PHFtau的AD大脑中降低。因为MT结合的这种丧失可能会通过破坏MTs的稳定性而损害缠结AD神经元的生存能力,我们询问是否可以通过使用冈田酸 (OK) 和calyculin-A (cl-a) 抑制培养的人神经元 (NT2N细胞) 中的蛋白磷酸酶1 (PP1) 和PP2A来引发这些事件。用OK和CL-A处理NT2N细胞会增加tau的磷酸化,降低tau与MTs的结合,并选择性解聚更稳定的去酪氨酸化MTs,而不是更不稳定的酪氨酸化MTs。值得注意的是,这导致了轴突的快速变性,轴突在更稳定的去红细胞化MTs中富集,并且PP2A参与了该级联事件的启动,因为PP2A而不是PP1与NT2N细胞中的MTs密切相关。这些研究表明,AD大脑脆弱神经元中PP2A的失活可能在正常tau转化为PHFtau,稳定MTs的解聚以及缠结神经元产生的轴突变性中起机械作用。
  • 【氧代雷莫因治疗慢性应激大鼠后,胆碱能和去甲肾上腺素能系统参与行为恢复。】 复制标题 收藏 收藏
    DOI:10.1016/j.neuroscience.2006.08.041 复制DOI
    作者列表:Srikumar BN,Raju TR,Shankaranarayana Rao BS
    BACKGROUND & AIMS: :Chronic stress in rats has been shown to impair learning and memory, and precipitate several affective disorders like depression and anxiety. The mechanisms involved in these stress-induced disorders and the possible reversal are poorly understood, thus limiting the number of drugs available for their treatment. Our earlier studies suggest cholinergic dysfunction as the underlying cause in the behavioral deficits following stress. Muscarinic cholinergic agonist, oxotremorine is demonstrated to have a beneficial effect in reversing brain injury-induced behavioral dysfunction. In this study, we have evaluated the effect of oxotremorine treatment on chronic restraint stress-induced cognitive deficits. Rats were subjected to restraint stress (6 h/day) for 21 days followed by oxotremorine treatment for 10 days. Spatial learning and memory was assessed in a partially baited eight-arm radial maze task. Stressed rats exhibited impairment in performance, with decreased percentage of correct choices and an increase in the number of reference memory errors (RMEs). Oxotremorine treatment (0.1 or 0.2 mg/kg, i.p.) to stressed rats resulted in a significant increase in the percent correct choices and a decrease in the number of RMEs compared with stress as well as the stress+vehicle-treated groups. In the retention test, oxotremorine treated rats committed less RMEs compared with the stress group. Chronic restraint stress decreased acetylcholinesterase (AChE) activity in the hippocampus, frontal cortex and septum, which was reversed by both the doses of oxotremorine. Further, oxotremorine treatment also restored the norepinephrine levels in the hippocampus and frontal cortex. Thus, this study demonstrates the potential of cholinergic muscarinic agonists and the involvement of both cholinergic and noradrenergic systems in the reversal of stress-induced learning and memory deficits.
    背景与目标: : 大鼠的慢性压力已被证明会损害学习和记忆,并引发几种情感障碍,如抑郁和焦虑。对这些应激引起的疾病的机制和可能的逆转知之甚少,因此限制了可用于治疗的药物数量。我们早期的研究表明,胆碱能功能障碍是压力后行为缺陷的根本原因。毒蕈碱胆碱能激动剂氧代吗啡被证明在逆转脑损伤引起的行为功能障碍方面具有有益作用。在这项研究中,我们评估了氧代吗啡治疗对慢性束缚应激引起的认知缺陷的影响。对大鼠进行约束应激 (6 h/天) 21天,然后进行氧代雷丁治疗10天。在部分诱饵的八臂径向迷宫任务中评估了空间学习和记忆。应激大鼠的表现受损,正确选择的百分比降低,参考记忆错误 (rme) 的数量增加。与应激以及应激 + 媒介物处理组相比,对应激大鼠进行氧代雷丁处理 (0.1或0.2 mg/kg,i.p.) 导致正确选择百分比显着增加,rme数量减少。在保留试验中,与应激组相比,氧代雷莫林处理的大鼠产生的RMEs较少。慢性束缚应激降低了海马,额叶皮层和隔膜中的乙酰胆碱酯酶 (AChE) 活性,这两种剂量的氧代雷莫林都可以逆转。此外,氧代吗啡治疗还恢复了海马和额叶皮层中的去甲肾上腺素水平。因此,这项研究证明了胆碱能毒蕈碱激动剂的潜力,以及胆碱能和去甲肾上腺素能系统参与逆转应激诱导的学习和记忆缺陷。
  • 【下丘脑galanin免疫反应性神经元投射到大鼠垂体后叶: 逆行追踪和免疫组织化学研究相结合。】 复制标题 收藏 收藏
    DOI:10.1002/cne.902990403 复制DOI
    作者列表:Arai R,Onteniente B,Trembleau A,Landry M,Calas A
    BACKGROUND & AIMS: UNLABELLED:To identify the galanin-immunoreactive neurons projecting to the posterior lobe of the pituitary in the rat hypothalamus, a retrograde tracer (complex of wheat germ agglutinin-enzymatically inactive horseradish peroxidase-colloidal gold) was injected into the posterior lobe of the pituitary. Sections of the hypothalamus were treated with a combination of silver enhancement of retrogradely transported tracer and immunohistochemistry of galanin. Of the total number of hypothalamic cells doubly labeled with retrograde tracing and galanin-immunostaining, 56-60% were found in the supraoptic nucleus, 18-23% in the retrochiasmatic nucleus, 8-10% in the lateral magnocellular portion of the paraventricular nucleus. The ratio of (number of doubly labeled cells/number of galanin-immunoreactive cells) in each of the above regions was similar to the ratio of (number of retrogradely labeled cells/number of Nissl-stained cells) in the supraoptic nucleus. Of all retrogradely labeled cells in the hypothalamus, 51-56% also contained galaninlike immunoreactivity. IN CONCLUSION:(1) galanin-immunoreactive fibers in the posterior lobe of the pituitary originate mainly in the supraoptic nucleus, retrochiasmatic nucleus, and lateral magnocellular portion of the paraventricular nucleus, (2) most of galanin-immunoreactive cells in these regions project to the posterior lobe of the pituitary, and (3) about half the neurons constituting the hypothalamo-neurohypophyseal system contain galaninlike immunoreactivity.
    背景与目标:
  • 【皮质神经元中的Na ()-Ca2交换电流: 伴随的正向和反向操作以及谷氨酸的作用。】 复制标题 收藏 收藏
    DOI:10.1111/j.1460-9568.1997.tb01482.x 复制DOI
    作者列表:Yu SP,Choi DW
    BACKGROUND & AIMS: Na(+)-Ca2+ exchanger-associated membrane currents were studied in cultured murine neocortical neurons, using whole-cell recording combined with intracellular perfusion. A net inward current specifically associated with forward (Na+(o)-Ca2+(i)) exchange was evoked at -40 mV by switching external 140 mM Li+ to 140 mM Na+. The voltage dependence of this current was consistent with that predicted for 3Na+1Ca2+ exchange. As expected, the current depended on internal Ca2+, and could be blocked by intracellular application of the exchanger inhibitory peptide, XIP. Raising internal Na+ from 3 to 20 mM or switching the external solution from 140 mM Li+ to 30 mM Na+ activated outward currents, consistent with reverse (Na+(i)-Ca2+(o)) exchange. An external Ca2(+)-sensitive current was also identified as associated with reverse Na(+)-Ca2+ exchange based on its internal Na+ dependence and sensitivity to XIP. Combined application of external Na+ and Ca2+ in the absence of internal Na+ triggered a 3.3-fold larger inward current than the current activated in the presence of 3 mM internal Na+, raising the intriguing possibility that Na(+)-Ca2+ exchangers might concurrently operate in both the forward and the reverse direction, perhaps in different subcellular locations. With this idea in mind, we examined the effect of excitotoxic glutamate receptor activation on exchanger operation. After 3-5 min of exposure to 100-200 microM glutamate, the forward exchanger current was significantly increased even when external Na+ was reduced to 100 mM, and the external Ca2(+)-activated reverse exchanger current was eliminated.

    背景与目标: 使用全细胞记录结合细胞内灌注,在培养的鼠新皮层神经元中研究了Na ()-Ca2交换剂相关的膜电流。通过将外部140 mM Li切换到140 mM Na,在40 mV时诱发了与正向 (Na (o)-Ca2 (i)) 交换特别相关的净向内电流。该电流的电压依赖性与3Na 1Ca2交换的预测一致。如预期的那样,电流取决于内部Ca2,并且可以通过在细胞内应用交换抑制肽XIP来阻断电流。将内部Na + 从3升高到20 mm或将外部溶液从140 mM Li + 切换到30mm Na + 激活的外向电流,与反向 (Na +(i)-Ca2 +(o)) 交换一致。根据其内部Na依赖性和对XIP的敏感性,还确定了对外部Ca2 () 敏感的电流与反向Na ()-Ca2交换有关。在不存在内部Na的情况下组合施加外部Na和Ca2触发的内向电流比在3毫米内部Na存在下激活的电流大3.3倍,提出了Na ()-Ca2交换剂可能同时在正向和反向同时运行的有趣可能性,也许在不同的亚细胞位置。考虑到这一想法,我们研究了兴奋性谷氨酸受体激活对交换器操作的影响。暴露于100-200 microM谷氨酸3-5分钟后,即使外部Na降低到100 mM,正向交换电流也显着增加,并且消除了外部Ca2 () 激活的反向交换电流。
  • 【投射在三叉神经和舌下运动核上的延髓吞咽神经元的轴突分支: 电生理和荧光双重标记技术的证明。】 复制标题 收藏 收藏
    DOI:10.1007/BF00228130 复制DOI
    作者列表:Amri M,Car A,Roman C
    BACKGROUND & AIMS: :The projections of ventral medullary reticular neurons on both trigeminal (Vth) and hypoglossal (XIIth) motor nucleus were studied in sheep anesthetized with halothane. In a first series of experiments, extracellular microelectrodes were used to record the activity of medullary swallowing interneurons (SINs) located in the ventral region (around the nucleus ambiguus) of the swallowing center. Antidromic activation after electrical stimulation of the Vth and XIIth nuclei was tested in 83 SINs. For 38 SINs a clear antidromic activation was observed and for 8 of them the response was triggered by stimulation of either nucleus. As confirmed by the reciprocal collision test, these 8 SINs had branched axons sending information to both nuclei tested. Average latencies for antidromic activation of branched SINs after stimulation of the XIIth and the Vth motor nucleus were 2.2 +/- 0.6 ms and 2.7 +/- 0.8 ms respectively. The axonal conduction velocity of these neurons was 4.4 +/- 1.3 m/s for the collateral to the Vth motor nucleus and 2.7 +/- 0.7 m/s for axons projecting to the XIith motor nucleus. In a second series of experiments the double retrograde labeling technique was used to confirm the existence of neurons with branched axons in the medullary regions corresponding to the swallowing center. Small and well localized injections of Fast Blue (FB) and Diamidino Yellow (DY) fluorescent tracers were made in the Vth and in the XIIth motor nucleus respectively. A relatively large number of double-labeled cells was found in the ventral region of swallowing center (reticular formation around the nucleus ambiguus, 2-4 mm in front of obex).(ABSTRACT TRUNCATED AT 250 WORDS)
    背景与目标: : 在氟烷麻醉的绵羊中研究了三叉神经 (Vth) 和舌下 (XIIth) 运动核上腹侧延髓网状神经元的投影。在第一系列实验中,细胞外微电极用于记录位于吞咽中心腹侧区域 (在核周围) 的髓质吞咽中间神经元 (SINs) 的活性。在83个SINs中测试了电刺激Vth和XIIth核后的反机器人激活。对于38个SINs,观察到明显的反机器人激活,其中8个是通过刺激任一核触发的。正如相互碰撞测试所证实的那样,这8个SINs具有分支的轴突,向两个测试的核发送信息。刺激XIIth和Vth运动核后,分支SINs的反抗激活的平均潜伏期分别为2.2/- 0.6 ms和2.7/- 0.8 ms。这些神经元的轴突传导速度对于Vth运动核的侧支为4.4/- 1.3 m/s,对于投射到XIith运动核的轴突为2.7/- 0.7 m/s。在第二系列实验中,使用双逆行标记技术来确认在对应于吞咽中心的髓质区域中存在具有分支轴突的神经元。分别在Vth和XIIth运动核中进行了快速蓝 (FB) 和二氨基黄 (DY) 荧光示踪剂的小且局部良好的注射。在吞咽中心的腹侧区域发现了相对大量的双标记细胞 (网状形成在核周围,在obex前面2-4毫米)。(摘要截短在250个单词)
  • 【枸杞多糖对原代培养大鼠海马神经元的作用机制。】 复制标题 收藏 收藏
    DOI:10.1007/s00441-017-2648-2 复制DOI
    作者列表:Zhao P,Ma NT,Chang RY,Li YX,Hao YJ,Yang WL,Zheng J,Niu Y,Sun T,Yu JQ
    BACKGROUND & AIMS: :Lycium barbarum polysaccharides (LBP) have been reported to have a wide range of beneficial effects including neuroprotection, anti-aging and anticancer. However, the anti-inflammation mechanism of LBP on primary cultured rat hippocampal neurons injured by oxygen-glucose deprivation/reperfusion (OGD/RP) is incompletely understood. We investigate the neuroprotective effects of LBP on neonatal rat primary cultured hippocampal neurons injured by OGD/RP with different approaches: MTT assay was used to detect cell viability, lactate dehydrogenase leakage was used to detect neuronal damage, formation of reactive oxygen species was determined by using fluorescent probe DCFH-DA. Hoechst 33,342 staining and TUNEL staining were used to determine the cell apoptosis. JC-1 was used to evaluate loss of mitochondrial membrane potential (MMP). The fluorescence intensity of [Ca2+]i in hippocampal neurons was determined by laser scanning confocal microscopy. The expression of various apoptotic markers such as TLR4, IκB, IL-6 and NF-κB were investigated by RT-PCR and western blot analysis. Results from each approach demonstrated that LBP increased the cell abilities and decreased the cell morphologic impairment. Furthermore, LBP increased MMP but inhibited [Ca2+]i elevation and significantly suppressed overexpression of NF-κB, IL-6 TLR4 and increased IκB expression.
    背景与目标: : 据报道,枸杞多糖 (LBP) 具有广泛的有益作用,包括神经保护,抗衰老和抗癌。然而,LBP对氧-葡萄糖剥夺/再灌注 (OGD/RP) 损伤的原代培养大鼠海马神经元的抗炎机制尚不完全清楚。我们用不同的方法研究了LBP对OGD/RP损伤的新生大鼠原代培养海马神经元的神经保护作用: MTT法检测细胞活力,乳酸脱氢酶渗漏法检测神经元损伤,活性氧的形成通过荧光探针DCFH-DA。Hoechst 33,342染色和TUNEL染色用于确定细胞凋亡。JC-1用于评估线粒体膜电位 (MMP) 的丧失。用激光扫描共聚焦显微镜测定海马神经元 [Ca2] i的荧光强度。通过rt-pcr和western blot分析研究了各种凋亡标志物 (如TLR4,i κ b,IL-6和NF-κ b) 的表达。每种方法的结果均表明,LBP可提高细胞能力并减少细胞形态损伤。此外,LBP增加了MMP,但抑制了 [Ca2] i的升高,并显着抑制了NF-κ b的过表达,IL-6 TLR4和增加了i κ b的表达。
  • 【阿尔茨海默氏病额叶皮层的毒蕈碱性胆碱感受性神经元。】 复制标题 收藏 收藏
    DOI:10.1016/0361-9230(91)90038-l 复制DOI
    作者列表:Schröder H,Giacobini E,Struble RG,Luiten PG,van der Zee EA,Zilles K,Strosberg AD
    BACKGROUND & AIMS: :The cellular distribution of muscarinic acetylcholine receptor protein in the frontal cortex of Alzheimer (AD) patients, age-matched and middle-aged controls was assessed quantitatively by means of immunohistochemistry using the monoclonal antibody M35. As shown previously in biopsy cortices, mainly layer II/III and V pyramidal neurons were immunolabeled. Neither distribution nor numbers of labeled cells displayed significant differences between the groups investigated. This is in accordance with the results of ligand binding studies that mostly failed to reveal different binding characteristics in AD compared to controls. Muscarinic and nicotinic receptor proteins have been shown to be colocalized in many cholinoceptive pyramidal neurons. Since nicotinic receptors--in contrast to muscarinic receptor proteins--are severely reduced in AD, this indicates a selective impairment of nicotinic receptor expression and not a significant death of cholinoceptive neurons per se.
    背景与目标: : 通过使用单克隆抗体m35的免疫组织化学方法定量评估了阿尔茨海默病 (AD) 患者,年龄匹配和中年对照的额叶皮层中毒蕈碱型乙酰胆碱受体蛋白的细胞分布。如先前在活检皮层中所示,主要对II/III层和V锥体神经元进行了免疫标记。在所研究的组之间,标记细胞的分布和数量均未显示出显着差异。这与配体结合研究的结果一致,该研究大多未能揭示与对照组相比在AD中的不同结合特性。毒蕈碱和烟碱受体蛋白已显示在许多胆碱感受性锥体神经元中共定位。由于烟碱受体-与毒蕈碱受体蛋白相反-在AD中严重减少,这表明烟碱受体表达的选择性损害,而不是胆碱感受性神经元本身的显着死亡。
  • 【大鼠腹侧被盖区的Orexin轴突很少突触到多巴胺和 γ-氨基丁酸神经元上。】 复制标题 收藏 收藏
    DOI:10.1002/cne.21420 复制DOI
    作者列表:Balcita-Pedicino JJ,Sesack SR
    BACKGROUND & AIMS: :Cells in the ventral tegmental area (VTA) facilitate motivated behaviors, and the activity of VTA neurons is regulated by dense projections from the lateral hypothalamic area (LHA). Orexin (Orx) neurons in the lateral and perifornical hypothalamus play important roles in arousal, feeding, and energy metabolism. Orx cells contribute substantially to the LHA projection to the rat midbrain. However, the morphological features of Orx fibers in the VTA and whether they synapse onto dopamine (DA) or gamma-aminobutyric acid (GABA) neurons have not yet been investigated. We utilized immunoperoxidase and immunogold-silver staining to examine the morphological features and synaptic incidence of Orx-labeled axons in the VTA. We then combined immunoperoxidase labeling for Orx with immunogold-silver labeling for GABA or for tyrosine hydroxylase (TH) in DA neurons. Electron microscopic analysis revealed that most Orx-labeled axons in the VTA were passing fibers. The less common Orx varicosities were occasionally apposed to TH- or GABA-labeled dendrites without synapsing. Only a small proportion of Orx-positive axons synapsed onto dendrites or soma. The synapses included both asymmetric and symmetric types and targeted TH- and GABA-labeled profiles with equal frequency. These findings suggest that most Orx fibers in the VTA are axons passing to caudal brainstem structures. However, Orx does mediate some direct synaptic influence on VTA DA and GABA neurons. Additional nonsynaptic effects are suggested by the presence of numerous dense-cored vesicles. These studies have important implications for understanding the mechanisms whereby Orx can alter behavior through regulating VTA DA and GABA cell activity.
    背景与目标: : 腹侧被盖区 (VTA) 中的细胞促进动机行为,并且VTA神经元的活动受下丘脑外侧区域 (LHA) 的密集投射调节。外侧和穹顶周围下丘脑的Orexin (Orx) 神经元在唤醒,进食和能量代谢中起重要作用。Orx细胞对大鼠中脑的LHA投射有很大贡献。然而,尚未研究VTA中Orx纤维的形态特征以及它们是否突触到多巴胺 (DA) 或 γ-氨基丁酸 (GABA) 神经元上。我们利用免疫过氧化物酶和免疫金银染色来检查VTA中Orx标记的轴突的形态特征和突触发生率。然后,我们将Orx的免疫过氧化物酶标记与DA神经元中GABA或酪氨酸羟化酶 (TH) 的免疫金银标记相结合。电子显微镜分析表明,VTA中大多数Orx标记的轴突都是通过的纤维。偶尔将不太常见的Orx静脉曲张与TH或GABA标记的树突相结合,而没有突触。只有一小部分Orx阳性轴突突触到树突或躯体上。突触包括不对称和对称类型,以及具有相同频率的靶向TH和GABA标记的轮廓。这些发现表明,VTA中的大多数Orx纤维是传递到尾脑干结构的轴突。然而,Orx确实介导了对VTA DA和GABA神经元的一些直接突触影响。由于存在许多致密的囊泡,因此提示了其他非突触作用。这些研究对于理解Orx通过调节VTA DA和GABA细胞活性来改变行为的机制具有重要意义。
  • 【“恢复活力” 保护帕金森氏病小鼠模型中的神经元。】 复制标题 收藏 收藏
    DOI:10.1038/nature05865 复制DOI
    作者列表:Chan CS,Guzman JN,Ilijic E,Mercer JN,Rick C,Tkatch T,Meredith GE,Surmeier DJ
    BACKGROUND & AIMS: :Why dopamine-containing neurons of the brain's substantia nigra pars compacta die in Parkinson's disease has been an enduring mystery. Our studies suggest that the unusual reliance of these neurons on L-type Ca(v)1.3 Ca2+ channels to drive their maintained, rhythmic pacemaking renders them vulnerable to stressors thought to contribute to disease progression. The reliance on these channels increases with age, as juvenile dopamine-containing neurons in the substantia nigra pars compacta use pacemaking mechanisms common to neurons not affected in Parkinson's disease. These mechanisms remain latent in adulthood, and blocking Ca(v)1.3 Ca2+ channels in adult neurons induces a reversion to the juvenile form of pacemaking. Such blocking ('rejuvenation') protects these neurons in both in vitro and in vivo models of Parkinson's disease, pointing to a new strategy that could slow or stop the progression of the disease.
    背景与目标: : 为什么大脑黑质的含多巴胺神经元在帕金森氏病中死亡一直是一个持久的谜。我们的研究表明,这些神经元对L型Ca(v)1.3 Ca2通道的异常依赖,以驱动其维持的节律性起搏,使其容易受到被认为有助于疾病进展的应激源的影响。对这些通道的依赖随着年龄的增长而增加,因为黑质致密部中含有多巴胺的少年神经元使用了帕金森氏病未受影响的神经元常见的起搏机制。这些机制在成年期仍然是潜在的,并且在成年神经元中阻断Ca(v)1.3 Ca2通道会导致恢复到幼年的起搏形式。这种阻断 (“恢复活力”) 在帕金森氏病的体外和体内模型中保护这些神经元,这表明了一种可以减缓或阻止疾病进展的新策略。
  • 【大鼠弓状核中酪氨酸羟化酶免疫反应神经元的精细结构组织。】 复制标题 收藏 收藏
    DOI:10.1002/cne.902390104 复制DOI
    作者列表:Piotte M,Beaudet A,Joh TH,Brawer JR
    BACKGROUND & AIMS: :The fine structure of the tyrosine hydroxylase (TH) immunoreactive neurons of the hypothalamic arcuate nucleus was examined by means of immunocytochemistry [peroxidase-antiperoxidase (PAP) method], utilizing an antibody against TH. Immunolabeled axon terminals were observed infrequently and were located predominantly in the lateral region, whereas numerous labeled perikarya and dendrites were found throughout the nucleus. The labeled terminals, containing primarily clear and occasionally dense core vesicles, were never observed in synaptic contact. On the other hand, unlabeled axon terminals were frequently seen synapsing on labeled dendrites. In addition, the labeled dendrites were often seen in direct apposition to other neuronal elements such as both labeled and unlabeled perikarya. In contrast, unlabeled dendrites were never seen apposed to labeled perikarya. Labeled dendrites also occurred in direct contact with one another and with unlabeled dendrites. Moreover, numerous labeled dendrites were encountered along tanycytic processes. Dendrites engaged in tanycytic appositions were occasionally partially encompassed by thin sheaths emanating from the tanycytic process. The extensive contact made by the labeled dendritic profiles on both labeled perikarya and dendrites suggests that tubero-infundibular dopaminergic (TIDA) cells may communicate with each other by means of dendritic release of dopamine. The presence of appositions between labeled dendrites and both unlabeled perikarya and dendrites suggests that the TIDA system also influences other neuronal populations through its dendrites. Finally, the dendrotanycytic relationship suggests that the TIDA system may play some role in the regulation of tanycytic function.
    背景与目标: : 利用针对TH的抗体,通过免疫细胞化学 [过氧化物酶-抗过氧化物酶 (PAP) 方法] 检查了下丘脑弓状核的酪氨酸羟化酶 (TH) 免疫反应性神经元的精细结构。很少观察到免疫标记的轴突末端,并且主要位于外侧区域,而在整个细胞核中发现了许多标记的周核和树突。在突触接触中从未观察到标记的末端,主要包含透明且偶尔密集的核心囊泡。另一方面,经常看到未标记的轴突末端在标记的树突上突触。此外,标记的树突通常与其他神经元元件 (例如标记的和未标记的perikarya) 直接并置。相反,从未见过未标记的树突与标记的perikarya相对应。标记的树突也发生在彼此之间以及与未标记的树突直接接触的情况下。此外,在tanycytic过程中遇到了许多标记的树突。参与单细胞结合的树突有时被单细胞过程发出的薄鞘部分包围。标记的树突状分布在标记的周核和树突上的广泛接触表明,结核-漏斗状多巴胺能 (TIDA) 细胞可以通过多巴胺的树突状释放相互交流。标记的树突与未标记的perior核和树突之间存在并置点,这表明TIDA系统还通过其树突影响其他神经元种群。最后,树突状细胞的关系表明TIDA系统可能在调节tanycytic功能中起一定作用。
  • 【大鼠正中网状核神经元对化学刺激和血压变化的反应。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Lin AM,Wang Y,Su CK,Lee EH,Kuo JS,Chai CY
    BACKGROUND & AIMS: :Previous studies have shown that paramedian reticular nucleus (PRN) possessed sympathetic and parasympathetic inhibitions on autonomic nervous system. In the present study, the cardiovascular reactions of PRN by locally-applied DL-homocysteic acid (DLH), acetylcholine (ACh), monoamines and electrophysiological properties of PRN neurons responding to intravenous injection of ACh and NE were studied in adult Sprague-Dawley rats. In PRN, electrical stimulation caused hypotension and mild bradycardia while microinjection of DLH, which excites only cell body of the neurons but not passing fibers, evoked similar responses. Furthermore, direct application of ACh, norepinephrine (NE) or serotonin (5-HT) in PRN also produced hypotension, suggesting that these putative neurotransmitters may be involved in the cardiovascular responses in PRN. The electrophysiological properties of PRN neurons were studied: Neurons in PRN could be categorized into three types according to their neuronal activities in response to the changes of systemic arterial blood pressure (SAP) by ACh or NE given intravenously. Type I neurons (25/69) were activated in the same direction of SAP changes. Type II neurons (17/69) responded opposite to the direction of SAP changes. Type III neurons (27/69) responded inconsistently to the changes of SAP. All the three types of neurons were excited by locally-applied DLH and possessed a similar unfiltered action potential duration of greater than 0.5 msec.
    背景与目标: : 先前的研究表明,正中网状核 (PRN) 对自主神经系统具有交感和副交感神经抑制作用。在本研究中,在成年Sprague-Dawley中研究了局部应用DL-同型半胱氨酸 (DLH),乙酰胆碱 (ACh),单胺和PRN神经元对静脉注射ACh和NE的反应的心血管反应。大鼠。在PRN中,电刺激引起低血压和轻度心动过缓,而微量注射DLH仅激发神经元的细胞体而不通过纤维,引起类似的反应。此外,在PRN中直接应用ACh,去甲肾上腺素 (NE) 或5-羟色胺 (5-HT) 也会产生低血压,这表明这些假定的神经递质可能与PRN的心血管反应有关。研究了PRN神经元的电生理特性: 根据静脉内给药的ACh或NE对全身动脉血压 (SAP) 变化的响应,PRN中的神经元可分为三种类型。I型神经元 (25/69) 在SAP变化的同一方向被激活。II型神经元 (17/69) 对SAP变化的方向相反。III型神经元 (27/69) 对SAP的变化反应不一致。所有三种类型的神经元均由局部应用的DLH激发,并具有大于0.5毫秒的类似的未经过滤的动作电位持续时间。

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