Dose- and time-dependent hippocampal cholinergic lesions induced by ethylcholine mustard aziridinium ion: Effects of nerve growth factor,GM1 ganglioside,and vitamin E

Ethylcholine mustard aziridinium ion (ECMA) was infused intracerebroventricularly (icv) to rats followed by measurement of two markers of presynaptic cholinergic neurons, choline acetyltransferase (ChAT) activity and high affinity choline transport (HAChT), in the hippocampus and cortex. Bilateral icv administration of 1, 2, or 3 nmol of ECMA per side produced dose-dependent reductions in each marker in the hippocampus, but not in the cortex, one week after treatment. Reductions of 52% and 46% for ChAT activity and HAChT, respectively, were produced in the hippocampus by 3 nmol ECMA. Measurement of these two markers at different times after icv infusion of 2 nmol ECMA/ventricle revealed that the activity of ChAT was reduced to a greater extent than was HAChT in the hippocampus 1 day and 1, 2, 4, and 6 weeks after treatment. The maximal reductions of ChAT activity and HAChT (61% and 53%, respectively) were reached between 1 and 2 weeks after ECMA administration. There was no evidence of regeneration of either marker at 4 or 6 weeks posttreatment. HAChT and ChAT activity in the cortex were not altered at any of the posttreatment times examined.ECMA-induced deficits in hippocampal ChAT activity and HAChT were not counteracted by the following treatments: (i) daily administration of GM₁ ganglioside (10 mg/kg, intraperitoneally (ip)) from the day prior to infusion of ECMA until 2 weeks later; (ii) daily administration of GM₁ ganglioside between 2 and 6 weeks after infusion of ECMA; and (iii) icv administration of nerve growth factor (NGF) twice per week for 2 weeks after ECMA treatment. Since similar treatments with NGF and GM₁ ganglioside ameliorate lesions induced by other methods, these results indicate that the mechanism of lesion formation and the surviving cellular components influence the functional effects of neurotrophic factors. In contrast to the above results, treatment with vitamin E significantly attenuated ECMA-induced deficits of ChAT activity and HAChT. Further studies of the effects of vitamin E on the development of ECMA-induced deficits may help to elucidate the mechanism action of ECMA.     

刺激皮肤感受野对大鼠多觉型伤害性感受器诱发放电的影响

在大鼠尾部,重复压力刺激皮肤感受野,当间隔时间小于2min时,多觉型伤害性感受器的单位放电数随间隔时间的缩短而减少。压力与辐射热交叉刺激同一感受野,随后刺激的放电数也显著减少。皮下注射致痛剂引起持续性放电的背景上,分别向感受野施加按压、辐射热或电针刺激,随着放电增多后出现一个放电减少的过程。刺激支配尾部的交感神经则使减少的放电显著增多。结果表明,多觉型伤害性感受器受到刺激兴奋后有个感受性降低的过程。本文讨论了这一过程在按摩、针灸缓解痛机制中的可能作用。     

电刺激猫小脑顶核对动脉血压和肾交感神经放电的影响

在38只麻醉及人工呼吸的猫,观察到电刺激小脑顶核嘴侧部能引起动脉血压显著升高;肾交感神经放电于刺激期间显著增加。去缓冲神经对刺激顶核所引起的血压反应的幅度和肾交感神经放电均无明显影响,但可明显延长血压反应升高相以及血压恢复期的时间。静脉注射氯庄定引起血压降低、心率减慢及肾交感神经放电的抑制,并能减弱刺激顶核引起的血压反应,但增强了刺激顶核引起的肾神经放电的变化。电解损毁延髓腹外侧面引起血压降低及肾交感神经放电的抑制,然而无论单侧还是双侧损毁延髓腹外侧面都不能阻断刺激顶核所引起的血压和肾交感神经放电的反应。以上结果表明,电刺激顶核能引起明显的心血管反应,其反应的下行性通路可能不通过延髓腹外侧面。     

CGRP immunoreactivity and NADPH-diaphorase in afferent nerves of the rat penis

Calcitonin gene-related peptide (CGRP)-immunoreactive afferent nerve fibers are abundant in the rat penis. In addition, NADPH-diaphorase, which stains for nitric oxide synthase, has been localized within both autonomic and sensory dorsal root ganglia (DRG) and may be part of an important biochemical pathway involved in penile tumescence. The purpose of this study was: 1) to examine the circuitry of afferent nerves that are CGRP immunoreactive from the L6 DRG, 2) to examine the possibility that there are NADPH-diaphorase-positive afferent fibers from the L6 DRG to the rat penis, and 3) to examine the localization and colocalization of CGRP and NADPH-diaphorase within L6 DRG afferent perikarya. Calcitonin gene-related peptide immunostaining in the penis was eliminated following a bilateral transection of the pudendal nerves, but was unchanged following a bilateral transection of the pelvic splanchnic or hypogastric nerves. The NADPH-diaphorase staining was not altered by any of the nerve transections. Injection of the retrograde axonal tracer fluorogold (FG) into the dorsum penis labeled perikarya in the L6 DRG. Although the majority of FG-labeled perikarya contained neither CGRP nor NADPH-diaphorase, small subpopulations of perikarya contained either CGRP immunoreactivity, NADPH-diaphorase, or both. A unilateral pudendal nerve transection virtually eliminated (>99%) FG labeling in the ipsilateral L6 DRG. These data suggest that NADPH-diaphorase and CGRP are present, either together or separately, within a subpopulation of penile afferent perikarya. In addition, CGRP-immunoreactive afferent nerve fibers reach the penis primarily via the pudendal nerves. Finally, NADPH-diaphorase-positive penile afferents may be another important source of nitric oxide (NO) for penile tumescence.     

The origin of the luteinizing hormone-releasing hormone (LHRH) neurons in newts (Cynops pyrrhogaster): the effect of olfactory placode ablation

Summary Neurons containing luteinizing hormone-releasing hormone (LHRH) are first detected in newt embryos (Cynops pyrrhogaster) in the olfactory epithelium and ventromedial portion of the olfactory nerve, after which they sequentially appear in the intracerebral course of the terminal nerve at prometamorphosis, and in the septo-preoptic area at postmetamorphosis. In adults, however, LHRH-immunoreactive cells are rarely seen in the nasal region, and their distribution shifts into the brain, suggesting their migration. In order to ascertain the origin and possible migration route of these neurons in newt larvae, the effect of unilateral or bilateral olfactory placodectomy on the LHRH neuronal system has been studied. Removal of the olfactory placode results in the absence of LHRH-immunoreactive cells in the nasal and brain regions of the operated side, whereas the subsequent growth and the LHRH-immunoreactive cellular distribution in the contralateral side are identical to those of normal larvae. Following bilateral placodectomy, no LHRH immunoreactivity is detected on either side of the olfactory-brain axis. These results suggest that LHRH neurons of the newt, Cynops pyrrhogaster, originate in the olfactory placode and then migrate into the brain during embryonic development.     

Reduced neuronal sensitivity to dieldrin and picrotoxinin in a cyclodiene-resistant strain of Drosophila melanogaster (Meigen).

Toxicological and neurophysiological studies were performed to characterize the resistance mechanism in a cyclodiene-resistant strain of Drosophila melanogaster (Maryland strain). Dieldrin had an LC50 of 0.058 ppm against the larvae of susceptible D. melanogaster (Oregon-R wild type) when formulated in the rearing media. The LC50 of the resistant Maryland strain was 10.8 ppm, giving a resistance ratio (LC50-Maryland/LC50-susceptible) of 186-fold. Suction electrode recordings were made from peripheral nerves of the larval central nervous system to test whether reduced nerve sensitivity played any role in the observed resistance. In susceptible preparations (n = 5), inhibition of nerve firing by 1 mM gamma-aminobutyric acid (GABA) was effectively antagonized within 3-10 min by 10 microM dieldrin. In contrast, 30 min incubations with 10 microM dieldrin had no effect on preparations from cyclodiene-resistant individuals (n = 5). Similarly, 10 microM picrotoxinin blocked GABA-dependent inhibition in susceptible nerve preparations (n = 3). In recordings from resistant insects (n = 4), picrotoxinin displayed either weak antagonism of GABA or hyperexcitation indistinguishable from susceptible preparations. These results demonstrate that cyclodiene resistance in the Maryland strain of D. melanogaster 1) is expressed in immature stages, 2) is present at the level of the nerve, and 3) extends to picrotoxinin, albeit at a reduced level compared with dieldrin. The possible role of an altered GABA receptor in this resistance is discussed.     

外周损伤引起成年大鼠体感皮层的功能重组

为了了解外周神经损伤对体感皮层分域组构的影响,在成年大鼠上观察了切断坐骨神经(SC)前、即刻和切断后数周内后爪皮层代表区的改变。在盐酸氯胺酮麻醉下,用微电极记录后爪皮肤轻触刺激在对侧体感皮层工区诱发的多单位反应,得出后爪的皮层代表区图。在16例中,8例大鼠观察了切断SC的即时效应。结果表明,不但SC代表区丧失皮肤反应性,原隐神经(SA)代表区的皮肤反应性也明显下降或消失,同时神经元自发活动也明显减弱。另8例大鼠在切断后数周内做了1～3次重复测定。在最初几天,原SA代表区范围内多数记录点的皮肤反应性仍未恢复,但在原SC代表区内,一些记录点转而对SA皮肤轻触刺激起反应。在随后数周内SA代表区进行性地扩张,占领了大部分原SC代表区。这一结果说明成年大鼠外周神经损伤可导致体感皮层发生显著的重组改变。     

颈动脉内注入腺苷对呼吸,血压和肾交感神经活动的影响

在33只麻醉家兔,观察了颈动脉内注入腺苷所诱发的平均动脉压、心率,呼吸和肾交感神经活动的变化。结果如下:(1)颈动脉内注入腺苷后,平均动脉压呈剂量依赖性下降;呼吸加快,深度变化不明显,剪断窦神经后注入腺苷,仍引起平均动脉压下降,而呼吸变化消失。(2)隔离的颈动脉窦灌流液内加入腺苷后,平均动脉压下降,心率减慢;颈动脉体(CB)失活后反应消失。(3)将腺苷灌注到颈动脉窦区后,平均动脉压下降,肾交感神经传出放电活动增加,CB 失活或剪断窦神经后,反应消失。由此提示:腺苷可作为兴奋 CB 的一种物质,引起平均动脉压降低,心率减慢,呼吸加强和肾交感神经放电活动增加。     

电离辐射引起胃排空延迟机理的初步探讨

本文观察了800rad照射后胃肠肌电的变化及切斷内脏神经与电刺激迷走神经对官的影响,初步分析了电离辐射引起胃排空延迟的机理。结果是:800rad照后大鼠胃肠肌电的峰波平均振幅胃幽部窦部照后1小时至第4天明显降低(P<0.05);幽门括约肌政变不大;十二指肠球部照后第3～7天明显下降(P<0.01)。切断内脏神经后照射大鼠胃肠肌电的峰波平均振幅胃幽门窦部变化不大,幽门括约肌照后1小时至第5天明显升高(P<0.05),十二指肠球部照后第3～7天明显下降(P<0.05)。800rad照后第4天大鼠胃对电刺激迷走神经的反应性明显降低(P<0.01)。上述结果表明:照后胃排空延迟的原因不仅与神经-体液调节紊乱有关,而且与射线损伤了平滑肌,使其兴奋性暂时的功能性降低有关。此外照后由于十二指肠球部运动的变化而使内感受器对胃运动的调节发生紊乱也是值得重视的因素。     

延髓中缝核区注射谷氨酸钠降低大鼠动脉血压的作用

本工作研究了大鼠延髓中缝核在心血管活动调整中的作用。通过埋植套管向大鼠延髓中缝核区注射神经元兴奋剂谷氨酸钠5-μg可明显降低血压,抑制交感神经传出活动,心率无显著改变。降血压效应可被脊髓蛛网膜下腔注射5-HT受体阻断剂肉桂硫胺50μg,或腹腔注射赛庚啶15mg/kg所部分对抗;并可被皮下注射阿片受体阻断剂纳洛酮1mc/kg所削弱。结果提示:延髓中缝核-脊髓5-HT下行通路对脊髓的血管调节功能起抑制性影响,内源性阿片样物质可能参与该机制。