Glial protein S100B modulates long-term neuronal synaptic plasticity

Glial cells are traditionally regarded as elements for structural support and ionic homeostasis, but have recently attracted attention as putative integral elements of the machinery involved in synaptic transmission and plasticity. Here, we demonstrate that calcium-binding protein S100B, which is synthesized in considerable amounts in astrocytes (a major glial cell subtype), modulates long-term synaptic plasticity. Mutant mice devoid of S100B developed normally and had no detectable abnormalities in the cytoarchitecture of the brain. These mutant mice, however, had strengthened synaptic plasticity as identified by enhanced long-term potentiation (LTP) in the hippocampal CA1 region. Perfusion of hippocampal slices with recombinant S100B proteins reversed the levels of LTP in the mutant slices to those of the wild-type slices, indicating that S100B might act extracellularly. In addition to enhanced LTP, mutant mice had enhanced spatial memory in the Morris water maze test and enhanced fear memory in the contextual fear conditioning. The results indicate that S100B is a glial modulator of neuronal synaptic plasticity and strengthen the notion that glial-neuronal interaction is important for information processing in the brain.     

Profound neuronal plasticity in response to inactivation of the dopamine transporter

The dopamine transporter (DAT) plays an important role in calibrating the duration and intensity of dopamine neurotransmission in the central nervous system. We have used a strain of mice in which the gene for the DAT has been genetically deleted to identify the DAT’s homeostatic role. We find that removal of the DAT dramatically prolongs the lifetime (300 times) of extracellular dopamine. Within the time frame of neurotransmission, no other processes besides diffusion can compensate for the lack of the DAT, and the absence of the DAT produces extensive adaptive changes to control dopamine neurotransmission. Despite the absence of a clearance mechanism, dopamine extracellular levels were only 5 times greater than control animals due to a 95% reduction in content and a 75% reduction in release. Paradoxically, dopamine synthesis rates are doubled despite a decrease of 90% in the levels of tyrosine hydroxylase and degradation is markedly enhanced. Thus, the DAT not only controls the duration of extracellular dopamine signals but also plays a critical role in regulating presynaptic dopamine homeostasis. It is interesting to consider that the switch to a dopamine-deficient, but functionally hyperactive, mode of neurotransmission observed in mice lacking the DAT may represent an extreme example of neuronal plasticity resulting from long-term psychostimulant abuse.     

Reactive oxygen species and nitric oxide mediate plasticity of neuronal calcium signaling

Reactive oxygen species (ROS) and nitric oxide (NO) are important participants in signal transduction that could provide the cellular basis for activity-dependent regulation of neuronal excitability. In young rat cortical brain slices and undifferentiated PC12 cells, paired application of depolarization/agonist stimulation and oxidation induces long-lasting potentiation of subsequent Ca(2+) signaling that is reversed by hypoxia. This potentiation critically depends on NO production and involves cellular ROS utilization. The ability to develop the Ca(2+) signal potentiation is regulated by the developmental stage of nerve tissue, decreasing markedly in adult rat cortical neurons and differentiated PC12 cells.     

Age-related impairments in neuronal plasticity markers and astrocytic GFAP and their reversal by late-onset short term dietary restriction

Recent studies on the effects of dietary restriction (DR) in rodents and primates have shown that even late-onset short-term regimens can bring about comparable beneficial changes seen in animals subjected to life-long DR. We studied the effect of aging on the expression of neural cell adhesion molecule (NCAM), its polysialylated form PSA-NCAM and astrocytic marker glial fibrillary acidic protein (GFAP) by immunohistofluorescent staining and immunoblotting in 1, 3, 6, 18 and 24 months old male wistar rats. Maximum expression of NCAM and PSA-NCAM was observed in sub-granular zone (SGZ) or granular cell layer (GCL) of hippocampus, arcuate region and paraventricular area of hypothalamus and piriform cortex layer II from 1 and 3 months old rats, thereafter, gradual downregulation was observed in 6, 18 and 24 months old rats. Progressive increase in astrocytic GFAP expression was noticed in these regions of brain with age. We further addressed whether DR initiated in late adulthood in 24 months old rats confers beneficial effects and can reverse changes in expression of NCAM, PSA-NCAM and GFAP. These results suggest that even late-onset short term DR regimen in old rats can have beneficial effects on neuroplasticity.     

强制性运动疗法对脑缺血后大鼠神经功能重塑的影响及机制探讨

目的 观察强制性运动疗法对脑缺血后大鼠神经功能重塑的影响,并探讨其机制.方法 将90只健康SD大鼠随机分为假手术组、模型组、运动疗法组各30只,3组大鼠均用3.5％水合氯醛1 mL/kg腹腔麻醉,取左侧颈部直切口,分离左颈总动脉、颈内动脉、颈外动脉（ECA）,电凝ECA分支,离断ECA.假手术组到此步为止,模型组、运动疗法组制备左侧大脑中动脉闭塞模型;脑缺血模型成功后7d,运动疗法组建立强制性运动疗法模型.参照改良的Bederson氏6级评分标准对各组大鼠进行神经功能缺损评分,采用原位杂交检测缺血侧大脑皮质及梗塞灶边缘区Nogo受体（NgR）及轴突再生脑源性神经营养因子（BDNF） mRNA,免疫印迹检测NgR、BDNF蛋白.结果 与模型组比较,运动疗法组在制模后2、4、8周神经功能缺损评分明显降低,NgR mRNA及蛋白表达降低,BDNFmRNA及蛋白表达升高（P均＜0.01）.结论 强制性运动疗法可以明显改善大鼠脑缺血后神经功能,其机制可能与下调NgR的表达、上调BDNF表达,从而促进神经功能重塑有关.     

Shift-driven modulations of spin-echo signals

Since the pioneering works of Carr-Purcell and Meiboom-Gill [Carr HY, Purcell EM (1954) Phys Rev 94:630; Meiboom S, Gill D (1985) Rev Sci Instrum 29:688], trains of π-pulses have featured amongst the main tools of quantum control. Echo trains find widespread use in nuclear magnetic resonance spectroscopy (NMR) and imaging (MRI), thanks to their ability to free the evolution of a spin-1/2 from several sources of decoherence. Spin echoes have also been researched in dynamic decoupling scenarios, for prolonging the lifetimes of quantum states or coherences. Inspired by this search we introduce a family of spin-echo sequences, which can still detect site-specific interactions like the chemical shift. This is achieved thanks to the presence of weak environmental fluctuations of common occurrence in high-field NMR--such as homonuclear spin-spin couplings or chemical/biochemical exchanges. Both intuitive and rigorous derivations of the resulting "selective dynamical recoupling" sequences are provided. Applications of these novel experiments are given for a variety of NMR scenarios including determinations of shift effects under inhomogeneities overwhelming individual chemical identities, and model-free characterizations of chemically exchanging partners.     

Identification of pyramidal cells as the critical elements in hippocampal neuronal plasticity during learning.

The activity of single neurons recorded from rabbit hippocampus during classical conditioning of the nictitating membrane reflex was studied. All cells were first categorized according to their responses after fornix stimulation--i.i., antidromic activation, orthodromic activation, or no activation. The majority of cells that were antidromically activated--pyramidal cells--showed a highly positive correlation between the pattern of unit discharge and the topography of the nicititating membrane response within trial periods. Units that were orthodromically driven by fornix stimulation tended to inhibit during the presentation of trial stimuli, whereas most non-activated cells maintained low spontaneous levels of activity at all times. Thus, the major output neurons of the hippocampus appear to be the neuroanatomical substrate for the large and rapidly developing neuronal plasticity induced by this classical conditioning paradigm.     

Enteric neuronal plasticity and a reduced number of interstitial cells of Cajal in hypertrophic rat ileum

Department of Physiology and Neuroscience, University of Lund, Sweden

Correspondence to: Dr E Ekblad, Department of Physiology and Neuroscience, Section of Neuroendocrine Cell Biology, University of Lund, Lund University Hospital, E-blocket vån 5, S-221 85 Lund, Sweden.

Accepted for publication 19 January 1998

Background—Partial obstruction of the ileum causes a notable hypertrophy of smooth muscle cells and enteric neurones in the proximally located intestine.
Aims—To study the expression of neuromessengers in the hypertrophic ileum of rat as little is known about neuromessenger plasticity under these conditions. To investigate the presence of interstitial cells of Cajal (ICC) in hypertrophic ileum.
Methods—Ileal hypertrophy was induced by circumferential application of a strip of plastic film for 18-24 days. Immunocytochemistry, in situ hybridisation, nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry, and ethidium bromide staining were used to investigate the number of enteric neurones expressing neuropeptides and nitric oxide synthase, and the frequency of ICC.
Results—In the hypertrophic ileum several neuronal populations showed changes in their expression of neuromessengers. Myenteric neurones expressing vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide, and galanin were notably increased in number. In submucous ganglia the number of VIP immunoreactive neurones decreased while those expressing VIP mRNA increased. NADPH diaphorase positive submucous neurones increased dramatically while the number of neuronal type nitric oxide synthase expressing ones was unchanged. The number of ICC decreased notably in hypertrophic ileum.
Conclusion—Enteric neurones change their levels of expression of neuromessengers in hypertrophic ileum. ICC are also affected. The changes are presumably part of an adaptive response to the increased work load.
(GUT 1998;:836-844)

Keywords: enteric nerves;  interstitial cells of Cajal;  hypertrophy;  neuropeptides;  nitric oxide;  neuronal plasticity

     

Reversible cholestatic hepatitis caused by acetohexamide

We report a case of cholestatic hepatitis accompanied by peripheral and hepatic eosinophilia in a patient taking acetohexamide for a period of 1.5 yr. Jaundice developed acutely and was accompanied by fever. After discontinuation of the drug, there was no evidence of further damage, with prompt normalization of liver enzymes, bilirubin, and eosinophil count.     

Reversible decrease of oxygen consumption by hyperoxia

The hemodynamic and metabolic effects of 90 minutes normobaric hyperoxia were studied in 20 critically ill patients (11 septic, 9 nonseptic) requiring mechanical ventilation with inspired O2 fraction (FIO2) less than 0.40. Thirty minutes after increasing the FIO2 to 1.0, arterial PO2 had increased from about 100 to about 400 mm Hg, and whole body oxygen uptake (VO2) was decreased 10 percent (p less than 0.05) due to an 18 percent decrease in O2 extraction ratio. During the subsequent 60 minutes of hyperoxia, there was no further significant change in VO2. Cardiac index did not change in hyperoxia, but it increased 10 percent (p less than 0.05) in recovery as systemic vascular resistance decreased. VO2 returned to baseline after 30 minutes recovery at original FIO2 due to increased O2 extraction as well as the increased cardiac output. The decrease in VO2 without a decrease in O2 delivery may reflect maldistribution of blood flow and functional O2 shunting to protect tissue from unphysiologically high PO2. While brief oxygenation is advisable before periods of hypoventilation, the present data suggest that hyperoxic ventilation in these patients with already adequate O2 delivery was counterproductive.     

Reversible encapsulation by self-assembling resorcinarene subunits

Encapsulation complexes are assemblies in which a reversibly formed host more or less completely surrounds guest molecules. Host structures held together by hydrogen bonds have lifetimes in organic solvents of milliseconds to hours, long enough to directly observe the encapsulated guest by NMR spectroscopy. We describe here the action of alkyl ammonium compounds as guests that gather up to six molecules of the host module to form encapsulation complexes. The stoichiometry of the complexes--the largest hydrogen-bonded host capsules to date--is determined by the size and concentration of the guest.     

Reversible Transformation by Urea of Contact-Inhibited Fibroblasts

200 mM urea elicits alterations of cell social behavior in vitro. In the presence of urea, contact inhibition of movement and growth is reduced compared to untreated fibroblastic cell populations. This reduction of contact inhibition is rapidly reversible, but reversal requires some cycloheximide-sensitive cellular process. Cells treated with urea are agglutinable by concanavalin A, suggesting that urea might remove some cell-surface component(s). A nondialyzable factor can, in fact, be detected in the supernatant medium of urea-treated cells. This active constituent appears to be heat-labile and trypsin-sensitive, and can itself restore normal contact-inhibitory behavior to cells maintained in the urea-transformed state by cycloheximide. This system may permit identification and characterization of surface components that are involved in regulating normal cell social behavior.     

Reversible dilated cardiomyopathy induced by methamphetamine

This brief report details the case of a woman who was thought, after extensive evaluation, to have idiopathic congestive cardiomyopathy. It was subsequently found that systolic ventricular dysfunction was due to amphetamine abuse, and that ventricular function normalized after discontinuation of this drug.     

Retention of embryonic features by an adult neuronal system capable of plasticity: polysialylated neural cell adhesion molecule in the hypothalamo-neurohypophysial system.

The neural cell adhesion molecule, N-CAM, changes at the cell surface during development, from a highly sialylated form [polysialic acid (PSA)-linked N-CAM, PSA-N-CAM] to several isoforms containing less sialic acid. N-CAM and its polysialic acid may serve to regulate cell apposition, thus affecting a variety of cell interactions. In the nervous system, PSA-N-CAM has until now been localized in developing tissues where it is thought to participate in the structuring of neuronal groups and tissue pattern formation. It has been proposed, however, that PSA-N-CAM may also be expressed in the adult, where it may take part in plasticity and cell reshaping. In the present study, the use of immunoblot and immunocytochemical procedures with a monoclonal antibody that specifically recognizes PSA-N-CAM revealed that the adult rat hypothalamo-neurohypophysial system, which undergoes important neuronal-glial and synaptic rearrangements in response to physiological stimuli, contains high levels of PSA-N-CAM immunoreactivity. The use of a polyclonal serum reacting with all N-CAM isoforms indicated that PSA-N-CAM is expressed together with "adult" forms of N-CAM. Light and electron microscopy demonstrated the presence of PSA-N-CAM immunoreactivity in the supraoptic and paraventricular nuclei of the hypothalamus and in the neurohypophysis; the immunoreactivity was seen in dendrites, axons, and terminals and in associated astrocytes but not in neuronal somata. We propose that the continued expression of PSA-N-CAM confers to magnocellular neurons and their astrocytes the ability to reversibly change their morphology in adulthood. In addition, our observations suggest that evidence for polysialylation may serve to identify other neuronal systems capable of morphological plasticity in the adult central nervous system.     

Reversible bone marrow aplasia induced by naproxen

Summary We report a case of reversible bone marrow aplasia related to the use of naproxen. A 71-year-old women developed severe pancytopenia after she had been treated with naproxen for more than 8 weeks. Bone marrow examination showed marked hypocellularity compatible with aplastic anemia. Full recovery of the pancytopenia and bone marrow was observed when naproxen was discontinued. Absence of exposure to other drugs and lack of underlying disorders known to cause bone marrow aplasia makes this case unique.