Regulation of nicotinic acetylcholine receptors by tyrosine kinases in the peripheral and central nervous system: same players, different roles

Nicotinic acetylcholine receptors (nAChRs) exist in many subtypes and are found in the peripheral and central nervous system where they mediate or modulate synaptic transmission. We review how tyrosine phosphorylation and kinases regulate muscle and neuronal nAChRs. Interestingly, although some of the same kinase players interact with the various receptor subtypes, the functional consequences are different. While concerted action of MuSK, Abl- and Src-family kinases (SFKs) regulates the synaptic distribution of nAChRs at the neuromuscular junction, SFKs activate heteromeric neuronal nAChRs in adrenal chromaffin cells, thereby enhancing catecholamine secretion. In contrast, the activity of homomeric neuronal nAChRs, as found in the hippocampus, is negatively regulated by tyrosine phosphorylation and SFKs. It appears that tyrosine kinases provide the means to regulate all nAChRs; but the functional consequences, even those caused by the same kinase family, are specific for each receptor subtype and location. Received 21 February 2006; received after revision 24 July 2006; accepted 30 August 2006     

蛋白激酶C阳性细胞在大鼠大脑皮质和海马结构的分布

目的：观察蛋白激酶C(PKC)阳性细胞在大鼠大脑皮质和海马结构的形态和分布，为更好地研究PKC在中枢神经系统的生理作用提供形态学的基础。方法：用免疫组织化学方法检测了大脑皮质和海马结构PKC阳性细胞的分布。结果：PKC阳性细胞脑体较小，多呈卵圆形，少数呈三角形，多数突起较短。PKC阳性细胞主要分布在大脑的额叶、顶叶、颞叶和枕叶的Ⅱ、Ⅲ和Ⅳ层，在杏仁海马移行区和杏仁梨状皮质移行区也有分布。海马结构中主要分布在下托和齿状回的颗粒层、海马CAI区的锥体层和辐射层。结论：在大脑皮质和海马结构有PKC阳性细胞的广泛分布。     

基于一致性的微电网分布式不对称功率分配控制

微电网中分布式发电可使微电网的电能质量增强,但线路阻抗不匹配时传统功率下垂控制方法不能保证负荷不对称功率的精确分配.针对此问题,提出了一种基于一致性和自适应虚拟阻抗的分布式负序功率均分控制方法.该方法通过引入负序虚拟阻抗使分布式发电单元按容量精确分配不对称负荷.设计了多智能体一致性算法,自适应调整负序虚拟阻抗,消除线路阻抗不匹配带来的影响,实现了不对称功率准确分配.仿真实验结果验证了该控制方案的正确性和有效性.     

NSE和ERα在老年人和AD病人大脑海马神经元中共表达

服用雌激素可以防止或延缓绝经后妇女患Alzhei mer病.神经元特异性烯醇化酶(NSE)为神经元特异性标记物.运用荧光免疫技术,观察了NSE和雌激素受体α(ERα)在老年人和AD病人大脑海马神经元中共存的分布.结果显示,在对照组和AD组NSE免疫阳性神经元均主要分布海马DG区的门区和CA4区.一些AD病人海马CA1、CA2和/或CA3没有观察到NSE免疫阳性反应.NSE免疫着色主要位于胞质和突起,部分区域也弥散于胞间质.ERα免疫反应广泛分布在老年人和AD病人海马神经元,且主要位于胞质,少量位于胞核.NSE和ERα免疫双标记主要分布在对照组海马门区和CA4区,而在AD组较少;且多着色于胞质.在老年组,多数NSE阳性神经元与ERα共着色,但仅有部分ERα阳性神经元NSE也着色.结果提示,雌激素可能通过其受体介导对神经元起保护作用的靶细胞仅为NSE和ERα双着色的那部分神经细胞.     

Effect of stress on choline acetyltransferase activity of the brain and the adrenal of the rat

Choline acetyltransferase (ChAT) activity was determined in cerebral cortex, hypothalamus, hippocampus, cerebellum, medulla oblongata, midbrain and adrenal gland of rats exposed to acute or chronic stress. The exposure of animals to acute immobilization and cold stress (4°C) for one hour resulted in a significant decline of ChAT activity in all brain regions examined except for the medulla oblongata. Moreover, the exposure to acute stress resulted in significant increase of the same enzyme in the adrenal gland. However, chronic exposure of animals to cold stress (4°C) for 7 days resulted in no significant changes of ChAT activity in all tissues examined except for a decline in the midbrain and an increase in the medulla oblongata. The administration of corticosterone (2.0 mg/kg) 1 h prior to sacrificing caused an effect similar to that of acute stress on ChAT activity in all brain regions except for the hypothalamus and the cerebellum. It was concluded from this experiment that stress-induced changes in the ChAT activity of specific brain regions might be mediated by the adrenal steroids.This work was supported by a grant from the National Aeronautics and Space Administration (NSG 2183 and NAG 2-411), a grant from the National Institutes of Health (NIH RR 0811) and a grant from the Division of Research Resources (NIH grant RR 03020).     

Reduction of high affinity glutamate uptake in rat hippocampus by two polyamine-like toxins isolated from the venom of the predatory waspphilanthus triangulum F

Summary Two components of the venom of the predatory waspPhilanthus triangulum F. significantly reduce — to a greater or less extent — the high affinity uptake of glutamate in rat hippocampus. A concentration of 10 M -PTX caused a reduction of 74%, while the other component, -PTX, at the same concentration, caused a reduction of 18%. Hence the effect of -PTX on high affinity glutamate uptake in the hippocampus is comparable with its effect on high affinity glutamate uptake in insect neuromuscular junctions. Contrary to our previous findings that -PTX has no effect on high affinity glutamate uptake in insect glutamatergic terminal axons, however, -PTX significantly reduces high affinity glutamate uptake in the hippocampus, albeit less effectively than -PTX.     

Effect of acute administration of Δ1-tetrahydrocannabinol on β-endorphin levels in plasma and brain tissue of the rat

Summary Acute treatment with ¹-tetrahydrocannabinol (¹-THC) elevated the concentration of -endorphin-like immunoreactivity (-ELIR) in plasma and in the hypothalamus, but not in the hippocampus of rats habituated to the injection procedure. These effects were not obtained with the psychotropically inert analog of (¹-THC), cannabidiol. In animals that had not been habituated to the injection procedure, placebo treatment induced a decrease in hippocampal -ELIR.The authors acknowledge the skillful technical assistance of Mrs Willeke Logtenberg.     

大白鼠海马神经元NOS与AChE活性的研究

目的:观察大白鼠海马不同亚区一氧化氮合酶(NOS)与乙酰胆碱酯酶(AChE)阳性神经元的活性。方法:分别采用还原型尼克酰胺嘌呤二核苷酸脱氢酶(NADPH-d)和乙酰胆碱酯酶(AChE)组织化学方法对大白鼠海马不同亚区NOS和AChE阳性神经元的分布以及活性进行研究。结果:海马不同亚区均含有NOS和AChE阳性神经元,其中CA2区NOS呈强阳性反应,CA3区AChE呈强阳性反应。结论:实验表明,NOS和AChE阳性神经元广泛分布于大白鼠海马不同亚区,为进一步探讨海马的学习记忆功能机制提供了形态学佐证。     

4-Aminopyridine and barium chloride attenuate the anti-epileptic effect of carbamazepine in hippocampal slices

Summary The exact mode of action of the anti-epileptic agent carbamazepine is unknown. In hippocampal slices in which epileptiform discharges were induced by addition of penicillin to the perfusion medium, the depressant effect of carbamazepine was attenuated by the potassium-channel blockers barium chloride (0.1 mM) and 4-aminopyridine (200 M), which suggested that potassium fluxes might be involved in the mechanism of action of carbamazepine.     

Autotaxin (NPP-2) in the brain: cell type-specific expression and regulation during development and after neurotrauma

Autotaxin is a secreted cell motility-stimulating exo-phosphodiesterase with lysophospholipase D activity that generates bioactive lysophosphatidic acid. Lysophosphatidic acid has been implicated in various neural cell functions such as neurite remodeling, demyelination, survival and inhibition of axon growth. Here, we report on the in vivo expression of autotaxin in the brain during development and following neurotrauma. We found that autotaxin is expressed in the proliferating subventricular and choroid plexus epithelium during embryonic development. After birth, autotaxin is mainly found in white matter areas in the central nervous system. In the adult brain, autotaxin is solely expressed in leptomeningeal cells and oligodendrocyte precursor cells. Following neurotrauma, autotaxin is strongly up-regulated in reactive astrocytes adjacent to the lesion. The present study revealed the cellular distribution of autotaxin in the developing and lesioned brain and implies a function of autotaxin in oligodendrocyte precursor cells and brain injuries. Received 18 September 2006; received after revision 30 October 2006; accepted 4 December 2006