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1.
  • Kanno, T, et al. (author)
  • Cellular function in multicellular system for hormone-secretion: electrophysiological aspect of studies on alpha-, beta- and delta-cells of the pancreatic islet
  • 2002
  • In: Neuroscience Research. - 0168-0102. ; 42:2, s. 79-90
  • Research review (peer-reviewed)abstract
    • We review a neck method to explore the cellular functions in multicellular system by application of the perforated patch-clamp technique to intact pancreatic islet of Langerhans. Using this approach, the integrity of the islet is preserved and intercellular communication via gap junctions and paracrine processes are maintained. 13 using low-resistance patch electrodes, rapid current responses can be monitored wider voltage-clamp control. We have applied this methodology to answer questions not resolved by patch-clamp experiments on isolated single insulin-secreting, beta-cells. First, the role of a K+-current dependent on Ca2+-influx for the termination of burst of action potentials in beta-cells could be documented. Neither the current, nor the bursting pattern of electrical activity is preserved in isolated beta-cells. Second. the conductance of gap junctions (similar to1 nS) between beta-cells was determined. Third, electrical properties of glucagon-producing alpha- and somatostatin-secreting delta-cells and the different mechanisms for glucose-sensing in these cells could be explored. The findings emanating from these experiments may hake implications for neuroscience research such as the mechanism of oscillatory electrical activity in general anti processes involved in the glucose-sensing in some neurons, which response to changes of blood glucose concentration. (C) 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
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6.
  • Abbas, Abdul-Karim, 1959, et al. (author)
  • Persistent LTP without triggered protein synthesis.
  • 2009
  • In: Neuroscience research. - : Elsevier BV. - 0168-0102. ; 63:1, s. 59-65
  • Journal article (peer-reviewed)abstract
    • Protein synthesis is believed to be involved in stabilizing synaptic plasticity. Effects lasting longer than about 2-3h are considered to require synthesis of new proteins, implying a functional separation between early (E) and late (L) components. However, the issue of constitutive vs. new protein synthesis is still unclear, especially in young animals. Here, we examined the effects of two protein synthesis inhibitors, anisomycin and emetine, on long-term-potentiation (LTP) in CA1 area of hippocampal slices from 12- to 20-day-old rats. Either drug was applied from -30 min to +30 min with respect to LTP induction, a time window previously reported to be critical. However, the LTP remained stable under the entire recording period of 4h (anisomycin), or 8h (emetine). Proper preparation of emetine solution was evidenced by the fact that, in separate experiments, prolonged treatment with emetine gradually blocked baseline responses. Although no corresponding effect was observed with anisomycin, the drug was judged to be potent by its ability to inhibit yeast growth. The ability of anisomycin to inhibit protein synthesis was further confirmed by radiolabeling experiments assessing the degree of leucine incorporation. Our data suggest that LTP up to at least 8h is not dependent on triggered protein synthesis but can be attained by utilizing proteins already available at induction time.
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8.
  • Benjaminsson, Simon, et al. (author)
  • Adaptive sensor drift counteraction by a modular neural network
  • 2010
  • In: Neuroscience research. - : Elsevier BV. - 0168-0102 .- 1872-8111. ; 68, s. E212-E212
  • Journal article (other academic/artistic)abstract
    • The response properties of sensors such as electronic noses vary in time due to internal or environmental factors. Recalibration is often costly or technically infeasible, which is why algorithms aimed at addressing the sensor drift problem at the data processing level have been developed. These falls in two categories: The pre-processing approaches, such as component correction [1], try to extract the direction and amount of drift in the training data and remove the drift component during operation. Adaptive algorithms, such as the self-organizing map [2], try to counteract the drift during runtime by adjusting the network to the incoming data.We have previously suggested a modular neural network architecture as a model of cortical layer 4 [3]. Here we show how it quite well can handle the sensor drift problem in chemosensor data. It creates a distributed and redundant code suitable for a noisy and drifting environment. A feature extraction layer governed by competitive learning allows for network adaptation during runtime. In addition, training data can be utilized to create a prediction of the underlying drift to further improve the network performance. Hence, we attempt to combine the two aforementioned methodological categories into one network model.The capabilities of the proposed network are demonstrated on surrogate data as well as real-world data collected from an electronic nose.
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9.
  • Bezard, Erwan, et al. (author)
  • Anti-dyskinetic effect of anpirtoline in animal models of L-DOPA-induced dyskinesia
  • 2013
  • In: Neuroscience Research. - : Elsevier BV. - 0168-0102. ; 77:4, s. 242-246
  • Journal article (peer-reviewed)abstract
    • The serotonin system has emerged as a potential target for anti-dyskinetic therapy in Parkinson's disease. In fact, serotonin neurons can convert L-DOPA into dopamine, and mediate its synaptic release. However, they lack a feedback control mechanism able to regulate synaptic dopamine levels, which leads to un-physiological stimulation of post-synaptic striatal dopamine receptors. Accordingly, drugs able to dampen the activity of serotonin neurons can suppress L-DOPA-induced dyskinesia in animal models of Parkinson's disease. Here, we investigated the ability of the 5-HT1A/1B receptor agonist anpirtoline to counteract LDOPA-induced dyskinesia in L-DOPA-primed 6-OHDA-lesioned rats and MPTP-treated macaques. Results suggest that anpirtoline dose-dependently reduced dyskinesia both in rats and monkeys; however, the effect in MPTP-treated macaques was accompanied by a worsening of the Parkinson's disease score at significantly effective doses (1.5 and 2.0 mg/kg). At a lower dose (0.75 mg/ kg), anpirtoline markedly reduced dyskinesia in 4 out of 5 subjects, but statistical significance was prevented by the presence of a non-responsive subject. These results provide further evidence that the serotonin neurons contribute both to the pro-dyskinetic effect of L-DOPA and to its therapeutic efficacy in the rat and monkey models of Parkinson's disease. (c) 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
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10.
  • Björklund, Martin, et al. (author)
  • Muscle stretch-induced modulation of noxiously activated dorsal horn neurons of feline spinal cord.
  • 2004
  • In: Neuroscience research. - : Elsevier BV. - 0168-0102 .- 1872-8111. ; 48:2, s. 175-184
  • Journal article (peer-reviewed)abstract
    • The present work was designed to check for the possibility of interactions between mechanical innocuous and chemically induced noxious muscle afferent inputs on discharge behavior of nociceptive superficial dorsal horn neurons (SDHNs) of the spinal cord in decerebrated cats. The innocuous and noxious stimuli were applied separately and in combination, so that the effects of the innocuous stimulus on nociceptive processing could be evaluated. The innocuous stimulus consisted of ramp-and-hold stretches of the gastrocnemius muscles, whereas the noxious stimulus consisted of i.a. injections of bradykinin (BK; 0.5-1 ml, 50 microg/ml) into the arterial circulation of same muscles. Only neurons up to approximately 1mm depth and those that responded to noxious pinch of the gastrocnemius muscles were selected for further analysis. The activity of 16 dorsal horn neurons was recorded extracellularly with high-impedance glass microelectrodes, out of which seven responded to stretch, while 12 neurons responded to bradykinin injections. The bradykinin injections induced three types of responses: excitatory, inhibitory and mixed. The majority of the neurons that showed excitatory and mixed responses to bradykinin were also influenced by stretches applied directly after the bradykinin injection. In these neurons, the stretch usually counteracted the bradykinin-induced response, i.e. shortening and reducing bradykinin-induced excitation and re-exciting the cells after bradykinin-induced inhibition. The mechanism of the stretch modulation is proposed to reside in a segmental spinal control of the nociceptive transmission.
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11.
  • Björkman, Anders, et al. (author)
  • Loss of inhibition in ipsilateral somatosensory areas following altered afferent nerve signaling from the hand
  • 2018
  • In: Neuroscience Research. - : Elsevier BV. - 0168-0102. ; 135, s. 32-36
  • Journal article (peer-reviewed)abstract
    • Cutaneous stimulation of the hand results in increased neural activity in the contralateral primary somatosensory cortex (S1) in humans, whereas an inhibition of neurons is seen in the ipsilateral S1.The aim of this study was to assess changes in neural activity in the S1 bilaterally, with a focus on the ipsilateral hemisphere, following altered afferent nerve signaling from the hand. Three cohorts, all with altered afferent nerve signaling from the hand, participated in the study. There were: 18 patients with traumatic median nerve injury, 10 patients with vibration induced neuropathy and 11 healthy subjects who had their dominant hand and wrist immobilized for 72 h. In addition, 36 healthy subjects were included as controls. Each subject was examined using functional magnetic resonance imaging at 3 T. All three study cohorts showed enlarged activation in the contralateral S1 during tactile stimulation compared to healthy controls. Moreover, inhibition of the ipsilateral S1 was significantly decreased or completely lost. Thus, somatosensory areas of both hemispheres respond to changed afferent nerve signaling from the hand. The loss of inhibition of neurons in the ipsilateral S1 suggests an important role of the ipsilateral hemisphere in the cerebral adaptation following a change in afferent nerve signaling.
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12.
  • Bogatikov, Evgenii, et al. (author)
  • miR-1933-3p is upregulated in skeletal muscles of MuSK+ EAMG mice and affects Impa1 and Mrpl27
  • 2020
  • In: Neuroscience research. - : Elsevier BV. - 0168-0102 .- 1872-8111. ; 151, s. 46-52
  • Journal article (peer-reviewed)abstract
    • MuSK antibody seropositive (MuSK+) Myasthenia Gravis (MG) typically affects skeletal muscles of the bulbar area, including the omohyoid muscle, causing focal fatigue, weakness and atrophy. The profile of circulating extracellular microRNA (miRNA) is changed in MuSK + MG, but the intracellular miRNA profile in skeletal muscles of MuSK + MG and MuSK + experimental autoimmune MG (EAMG) remains unknown. This study elucidated the intracellular miRNA profile in the omohyoid muscle of mice with MuSK + EAMG. The levels of eleven mouse miRNAs were elevated and two mouse miRNAs were reduced in muscles of MuSK + EAMG mice. Transient expression of miR-1933-3p and miR-1930-5p in mouse muscle (C2C12) cells revealed several downregulated genes, out of which five had predicted binding sites for miR-1933-3p. The mRNA expression of mitochondrial ribosomal protein L27 (Mrpl27) and Inositol monophosphatase I (Impa1) was reduced in miR-1933-3p transfected C2C12 cells compared to control cells (p = 0.032 versus p = 0.020). Further, transient expression of miR-1933-3p reduced Impa1 protein accumulation in C2C12 cells. These findings provide novel insights of dysregulated miRNAs and their intracellular pathways in muscle tissue afflicted with MuSK + EAMG, providing a possible link to mitochondrial dysfunction and muscle atrophy observed in MuSK + MG.
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13.
  • Brohlin, Maria, et al. (author)
  • Characterisation of human mesenchymal stem cells following differentiation into Schwann cell-like cells
  • 2009
  • In: Neuroscience research. - : Elsevier BV. - 0168-0102 .- 1872-8111. ; 64:1, s. 41-49
  • Journal article (peer-reviewed)abstract
    • Cell-based therapies provide a clinically applicable and available alternative to nerve autografts. Our previous studies have characterised rat-derived mesenchymal stem cells (MSC) and here we have investigated the phenotypic, molecular and functional characteristics of human-derived MSC (hMSC) differentiated along a Schwann cell lineage. The hMSC were isolated from healthy human donors and the identity of the undifferentiated hMSC was confirmed by the detection of MSC specific cells surface markers. The hMSC were differentiated along a glial cell lineage using an established cocktail of growth factors including glial growth factor-2. Following differentiation, the hMSC expressed the key Schwann cell (SC) markers at both the transcriptional and translational level. More importantly, we show the functional effect of hMSC on neurite outgrowth using an in vitro co-culture model system with rat-derived primary sensory neurons. The number of DRG sprouting neurites was significantly enhanced in the presence of differentiated hMSC; neurite length and density (branching) were also increased. These results provide evidence that hMSC can undergo molecular, morphological and functional changes to adopt a SC-like behaviour and, therefore, could be suitable as SC substitutes for nerve repair in clinical applications.
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  • Chauhan, Mayank, et al. (author)
  • Muscle-specific regulation of the mTOR signaling pathway in MuSK antibody seropositive (MuSK plus ) experimental autoimmune Myasthenia gravis (EAMG)
  • 2013
  • In: Neuroscience research. - : Elsevier BV. - 0168-0102 .- 1872-8111. ; 77:1-2, s. 102-109
  • Journal article (peer-reviewed)abstract
    • Myasthenia gravis (MG) patients with antibodies against muscle specific tyrosine kinase (MuSK+) typically present focal fatigue and atrophy of the facial and bulbar muscles, including the masseter muscle, whereas leg muscles often are clinically spared. This study addresses the regulation of the mTOR signaling pathway in the masseter muscle versus the leg muscle tibialis anterior (TA). We analyzed muscle morphology, protein levels of mTOR components as well as atrogenes and mitochondrial markers in these muscles of healthy control mice and mice with different clinical severity grades of MuSK+ experimental autoimmune MG (EAMG). Protein levels of mTOR components were reduced in the atrophic masseter muscle of MuSK+ EAMG mice, whereas enhanced accumulation of mTOR components was observed in the TA muscles. Two other muscles: omohyoid and soleus showed intermediate spectra. In conclusion, the anabolic mTOR signaling pathway is differentially regulated even in muscles with the same activity pattern in the same neuromuscular disease. This could in part explain the clinical phenotype in MuSK+ EAMG as well as in muscular dystrophies.
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15.
  • Dozmorov, Mikhail, 1973, et al. (author)
  • Contribution of AMPA and NMDA receptors to early and late phases of LTP in hippocampal slices.
  • 2006
  • In: Neuroscience research. - : Elsevier BV. - 0168-0102. ; 55:2, s. 182-8
  • Journal article (peer-reviewed)abstract
    • Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor mediated responses were investigated in rat hippocampal slices under 4h of long-term potentiation (LTP) expression. A modified medium containing the NMDA receptor antagonist AP5 and low concentration of Mg(2+) was used to monitor isolated AMPA responses. NMDA components were determined from composite excitatory postsynaptic potentials (EPSPs) under brief (15-20 min) wash-out of AP5. LTP was induced in a medium with low concentration of AP5, resulting in an about two-fold larger increase of the AMPA component than of the NMDA component at both 1h and 4h after induction. Similar results were obtained if LTP was induced in "normal Mg(2+)" and the NMDA components were assessed at the end of experiment, from either composite or isolated NMDA EPSPs, with or without blockade of GABAergic inhibition. It is generally believed that LTP undergoes biochemical and/or structural conversions during the first few hours. Our study, however, shows constant expression of LTP, at least in terms of AMPA versus NMDA components, during this time. The data support the notion that LTP initiates as a predominant amplification of AMPA receptors and remains so for at least 4h.
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16.
  • Eliasson, Moa, et al. (author)
  • Spider monkeys (Ateles geoffroyi) are less sensitive to the odor of aliphatic ketones than to the odor of other classes of aliphatic compounds.
  • 2015
  • In: Neuroscience research. - : Elsevier. - 0168-0102 .- 1872-8111. ; 99, s. 46-54
  • Journal article (peer-reviewed)abstract
    • Aliphatic ketones are widely present in body-borne and food odors of primates. Therefore, we used an operant conditioning paradigm and determined olfactory detection thresholds in four spider monkeys for a homologous series of aliphatic 2-ketones (2-butanone to 2-nonanone) and two of their isomers (3- and 4-heptanone). We found that, with the exception of the two shortest-chained ketones, all animals detected concentrations <1ppm (parts per million), and with five odorants individual animals even reached threshold values <0.1ppm. Further, we found a significant correlation between olfactory sensitivity of the spider monkeys and carbon chain length of the 2-ketones which can best be described as a U-shaped function. In contrast, no significant correlation was found between olfactory sensitivity and position of the functional carbonyl group. Across-odorant and across-species comparisons revealed the following: spider monkeys are significantly less sensitive to the odors of aliphatic ketones than to the odor of other classes of aliphatic compounds (1-alcohols, n-aldehydes, n-acetic esters, and n-carboxylic acids) sharing the same carbon length. Spider monkeys do not differ significantly in their olfactory sensitivity for aliphatic ketones from squirrel monkeys and pigtail macaques, but are significantly less sensitive to these odorants compared to human subjects and mice. These findings support the notion that neuroanatomical and genetic properties do not allow for reliable predictions with regard to a species' olfactory sensitivity. Further, we conclude that the frequency of occurrence of a class of odorants in a species' chemical environment does not allow for reliable predictions of the species' olfactory sensitivity.
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  • Forsman, Lea J, et al. (author)
  • Differences in regional brain volume related to the extraversion–introversion dimension : a voxel based morphometry study
  • 2012
  • In: Neuroscience research. - : Elsevier. - 0168-0102 .- 1872-8111. ; 72:1, s. 59-67
  • Journal article (peer-reviewed)abstract
    • Extraverted individuals are sociable, behaviorally active, and happy. We report data from a voxel based morphometry study investigating, for the first time, if regional volume in gray and white matter brain regions is related to extraversion. For both gray and white matter, all correlations between extraversion and regional brain volume were negative, i.e. the regions were larger in introverts. Gray matter correlations were found in regions that included the right prefrontal cortex and the cortex around the right temporo–parietal junction – regions that are known to be involved in behavioral inhibition, introspection, and social-emotional processing, e.g. evaluation of social stimuli and reasoning about the mental states of others. White matter correlations extended from the brainstem to widespread cortical regions, and were largely due to global effects, i.e. a larger total white matter volume in introverts. We speculate that these white matter findings may reflect differences in ascending modulatory projections affecting cortical regions involved in behavioral regulation.
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  • Huang, Fen-Sheng, 1961, et al. (author)
  • Bidirectional synaptic plasticity in response to single or paired pulse activation of NMDA receptors.
  • 2010
  • In: Neuroscience research. - : Elsevier BV. - 1872-8111 .- 0168-0102. ; 67:2, s. 108-116
  • Journal article (peer-reviewed)abstract
    • It is still incompletely known how NMDA receptors (NMDA-R) regulate bidirectional synaptic plasticity. We examined this issue by an experimental protocol in which paired pulse stimulation (PPS) with 50ms interstimulus interval and basal frequency of 0.1Hz was applied to CA1 area of rat hippocampal slices during low Mg(2+) perfusion. Under blockade of NMDA-Rs by AP5, PPS for 12-60min led to only a minor depression. In contrast, when PPS was applied in the absence of AP5, there was a prominent short-term potentiation (STP), mainly of AMPA-R mediated responses, with peak at 1min and lasting 10-15min. The STP was followed by a slowly developing long-term depression (LTD). Applying AP5 during the STP, converted it to a stable increase relative to the control pathway. Following peak STP, plasticity was controlled in a composite manner. Whereas the initial decay was counteracted by NMDA-R activation, the following LTD was dependent on such activation. Our data suggest that synaptic changes do not only depend on the instantaneous, NMDA-dependent Ca(2+) concentration in the dendritic spine, but are also influenced by prior induction events. In addition to NMDA-R driven processes, passive relaxation contributes to the synaptic plasticity and in some cases outbalances the active control.
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  • Larsson, Linda, et al. (author)
  • Ultra-high olfactory sensitivity for the human sperm-attractant aromaticaldehyde bourgeonal in CD-1 mice
  • 2011
  • In: Neuroscience research. - : Elsevier Ireland Ltd and the Japan Neuroscience Society. - 0168-0102 .- 1872-8111. ; 71:4, s. 355-360
  • Journal article (peer-reviewed)abstract
    • Recent studies have shown that certain aromatic aldehydes are ligands for olfactory receptors expressedin mammalian sperm cells and induce sperm chemotaxis. Using a conditioning paradigm, the olfactorysensitivity of five CD-1 mice for seven aromatic aldehydes was investigated. With all seven stimuli, themice discriminated concentrations as low as 0.01 ppm (parts per million) from the solvent, and withbourgeonal the animals even detected concentrations as low as 0.1 ppq (parts per quadrillion) whichconstitutes the lowest olfactory detection threshold value reported in this species so far. The presence ofa tertiary butyl group in para-position (relative to the functional aldehyde group) combined with a lack ofan additional alkyl group next to the functional aldehyde group may be responsible for the extraordinarysensitivity of the mice for bourgeonal.
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29.
  • Madhusudanan, Pallavi, et al. (author)
  • Nerve terminals in the tumor microenvironment as targets for local infiltration analgesia
  • 2023
  • In: Neuroscience research. - : Elsevier. - 0168-0102 .- 1872-8111. ; 196, s. 40-51
  • Journal article (peer-reviewed)abstract
    • Nerve terminals within the tumor microenvironment as potential pain-mitigating targets for local infiltration analgesia is relatively less explored. In this study, we examine the role of key analgesics administered as local infiltration analgesia in a model of cancer-induced bone pain (CIBP). CIBP was induced by administration of allogenic MRMT1 breast cancer cells in the proximal tibia of rats, and tumor mass characterized using radiogram, micro-CT, and histological analysis. In vitro responsiveness to key analgesics delta-opioid receptor agonist (DOPr), Ca2+ channel and TRPV1 antagonists was assessed using ratiometric Ca2+ imaging in sensory neurons innervating the tumor site. Effectiveness of locally infiltrated analgesics administered independently or in combination was assessed by quantifying evoked limb withdrawal thresholds at two distinct sites for up to 14 days. CIBP animals demonstrated DOPr, N-, and L-type and TRPV1 expression in lumbar dorsal root ganglion neurons (DRG), comparable to controls. Evoked Ca2+ transients in DRG neurons from CIBP animals were significantly reduced in response to treatment with compounds targeting DOPr, N-, L-type Ca2+ channels and TRPV1 proteins. Behaviourally, evoked hyperalgesia at the tumor site was strongly mitigated by peritumoral injection of the DOPr agonist and T-type calcium antagonist, via its activity on bone afferents. Results from this study suggest that nerve terminals at tumor site could be utilized as targets for specific analgesics, using local infiltration analgesia.
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30.
  • Mattsson, Niklas, 1979, et al. (author)
  • Converging molecular pathways in human neural development and degeneration.
  • 2010
  • In: Neuroscience research. - : Elsevier BV. - 1872-8111 .- 0168-0102. ; 66:3, s. 330-2
  • Journal article (peer-reviewed)abstract
    • Animal studies suggest that phosphorylation of microtubule-associated protein tau is a physiological way of destabilizing axons in the developing brain, promoting synaptic plasticity, while in the adult human brain tau phosphorylation is a specific sign of Alzheimer's disease. We here show, for the first time, that newborn human infants have extremely high levels of phosphorylated tau in their cerebrospinal fluid, and that these levels decrease during the first years of life. Tau phosphorylation in Alzheimer's disease may be a physiological response to Alzheimer-associated synaptotoxicity.
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  • Persson, Anders I., 1973, et al. (author)
  • Comparison of immunoblotted delta opioid receptor proteins expressed in the adult rat brain and their regulation by growth hormone.
  • 2005
  • In: Neuroscience research. - : Elsevier BV. - 0168-0102. ; 52:1, s. 1-9
  • Journal article (peer-reviewed)abstract
    • It has previously been suggested that exogenous growth hormone (GH) affect quality of life and higher brain functions through the endogenous opioid system. Recently, we showed that GH down-regulate 72 and 48 kDa delta opioid receptor (DOR) proteins in the adult rat cerebral cortex and cerebellum. In the present study, we found that an antiserum raised against the N-terminus of the DOR also recognizes a 36 kDa protein, not recognized by a C-terminus-directed antiserum. We aimed to investigate the identity of the 72, 48 and 36 kDa proteins and to further study the effects of GH on their expression in different brain regions. The expression was studied in hypophysectomized (Hx) and untreated normal female rats. One subgroup of Hx rats received GH as a daily subcutaneous injection for 19 days. Our data show that treatment with GH in Hx rats normalized the expression of the 72 kDa protein in the cerebral cortex, whereas no significant effect were observed for the 48 or 36 kDa proteins. However, GH significantly reduced the ratio between the 72 and 36 kDa proteins in different brain regions of Hx rats. Our data suggest that GH reduces the levels of a 72 kDa DOR that likely represents a dimeric form of a 36 kDa DOR post-translationally truncated at the C-terminus, and that altered receptor dimerization may be involved in GH induced effects in the central nervous system.
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36.
  • Reid, Adam J, et al. (author)
  • N-acetylcysteine alters apoptotic gene expression in axotomised primary sensory afferent subpopulations.
  • 2009
  • In: Neuroscience research. - : Elsevier BV. - 0168-0102 .- 1872-8111. ; 65:2, s. 148-155
  • Journal article (peer-reviewed)abstract
    • Novel approaches are required in peripheral nerve injury management because current surgical techniques, which do not address axotomy-induced neuronal death, lead to deficient sensory recovery. Sensory neuronal death has functional preference with cutaneous neurons dying in great numbers whilst muscle afferents survive axotomy. This offers the potential of comparing similar cell types that suffer distinct fates upon nerve injury. Here, a novel approach, combining in vivo rat nerve injury model with laser microdissection and quantitative real-time polymerase chain reaction, identifies crucial disparities in apoptotic gene expression attributable to subpopulations of differing sensory modalities and examines the response to N-acetylcysteine (NAC) therapy. We show that axotomised muscle afferent neurons survive injury due to a neuroprotective response which markedly downregulates Bax and caspase-3 mRNA. In contrast, axotomised cutaneous sensory neurons significantly upregulate caspase-3 and alter both Bcl-2 and Bax expression such that pro-apoptotic Bax predominates. N-Acetylcysteine (NAC) intervention promotes neuroprotection of cutaneous sensory neurons through considerable upregulation of Bcl-2 and downregulation of both Bax and caspase-3 mRNA. The data presented identifies differential activation of apoptotic genes in axotomised neuronal subpopulations. Furthermore, NAC therapy instigates apoptotic gene expression changes in axotomised neurons, thereby offering pharmacotherapeutic potential in the clinical treatment of nerve injury.
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37.
  • Schomburg, E D, et al. (author)
  • Nociceptive input to ascending tract neurones forwarding information from low threshold cutaneous and muscle afferents in cats.
  • 2000
  • In: Neuroscience research. - 0168-0102. ; 38:1, s. 117-20
  • Journal article (peer-reviewed)abstract
    • Effects of noxious skin stimulation (central foot pad and foot dorsum) by radiant heat were tested on neurones of ascending tracts with a main input from non-nociceptors. The dominating effect on ventral spinocerebellar tract neurones was a depression (mainly from the pad). Responses of spinocervical tract neurones were either facilitated (predominantly from the foot dorsum) or depressed (predominantly from the pad). The dominating effect on neurones tentatively classified as dorsal horn dorsal spinocerebellar tract neurones was facilitatory from both skin areas. Similar effects were evoked by selective actions of C-fibres when A-delta fibres were blocked by TTX.
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38.
  • Schomburg, E D, et al. (author)
  • Nociceptive input to spinal interneurones in reflex pathways from group II muscle afferents in cats.
  • 2000
  • In: Neuroscience research. - 0168-0102. ; 38:4, s. 447-50
  • Journal article (peer-reviewed)abstract
    • Effects of noxious stimulation of the skin by radiant heat were tested on responses of first order interneurones in reflex pathways from group II muscle afferents in mid-lumbar, lower-lumbar and sacral segments of the spinal cord. In mid- and lower-lumbar segments both background discharges and monosynaptically evoked responses of intermediate zone interneurones were facilitated. Those of mid-lumbar dorsal horn interneurones were also facilitated suggesting that both these interneuronal populations contribute to the facilitation of flexion reflexes by nociceptors. In contrast, the dominating effects of noxious heat on sacral dorsal horn group II interneurones were inhibitory. The effects evoked by selective activation of C fibres, after A-delta fibres had been blocked by TTX, were similar to those obtained before TTX application.
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40.
  • Skoglund, Thomas, 1969, et al. (author)
  • Aspects of the organization of neurons and dendritic bundles in primary somatosensory cortex of the rat
  • 2004
  • In: Neurosci Res. - : Elsevier BV. - 0168-0102. ; 50:2, s. 189-98
  • Journal article (peer-reviewed)abstract
    • In order to analyze some aspects of the spatial organization in the primary somatosensory cortex of the rat, we have reconstructed the positions of bundles of apical dendrites and neurons in a cortical prisms measuring 0.5 mm x 0.4 mm x cortical thickness, with special reference to a hypothetical columnar organization. Complete series of semithin (0.65 microm) sections were cut, tangentially from the pial surface down to the white matter, stained and digitizalized into a computer and represented as a stack of 2D images. The mean neuron density (N(V)-value) was (60 x 10(3) +/- 15 x 10(3)) neurons/mm3. The mean number of neurons beneath 1 mm2 of cortical surface (NC-value) was (113 x 10(3) +/- 8 x 10(3)) neurons/mm2. Well-defined bundles of apical dendrites emanating from layer V pyramidal cells were observed. The bundles consisted of 3-12 (mean 5 +/- 2) dendrites. The dendrites within a bundle converged while ascending towards the pial surface and reached a maximal close packing in layer IV. Superficially, the packing density decreased again. The mutual positions of the dendrites within the bundles shifted only slightly along their course towards the pial surface. The occurrence of bundles in tangential sections through layer IV was about 190 bundles/mm2 and the average number of neurons per bundle was estimated at approximately 600. However, when calculating Voronoi-diagrams, the number of neurons, which with this mathematical technique, is ascribed to each of the reconstructed dendritic bundles, varied between 200 and 1000. The possibility that the dendritic bundles are centers in cortical cell modules is discussed.
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42.
  • Tronci, Elisabetta, et al. (author)
  • Amphetamine-induced rotation and l-DOPA-induced dyskinesia in the rat 6-OHDA model: A correlation study.
  • 2012
  • In: Neuroscience Research. - : Elsevier BV. - 0168-0102. ; 73:2, s. 168-172
  • Journal article (peer-reviewed)abstract
    • The present study investigated whether the rotation rate induced by amphetamine in 6-OHDA-lesioned rats was predictive of development of l-DOPA-induced dyskinesia (LID) and success of the lesion procedure in our experimental settings. We collected data from 312 6-OHDA-lesioned rats (from different sets of experiments). Rats were subjected to the amphetamine-induced rotation test (2.5mg/kg) and chronically treated with l-DOPA (6mg/kg) to establish dyskinesia. A poor correlation was present between amphetamine-induced rotation and LID. Moreover, no correlation was found between amphetamine-induced rotation and tyrosine hydroxylase (TH) positive cell number in the lesioned substantia nigra pars compacta, while there was a weak correlation between the percentage of TH positive cell number and LID. These results indicate that the amphetamine-induced rotation test is a poor predictor of the 6-OHDA-lesion success, as well as of the development of LID at the dose of amphetamine used here. Our data also suggest that all rats with amphetamine-induced rotation ≥3turns/min should be included in dyskinesia studies, as they showed the same propensity to develop dyskinesia. Moreover, SERT expression levels suggest that reduced striatal and pallidal serotonin innervation might have contributed to the lower dyskinesia levels observed in a subset of amphetamine-responsive rats.
  •  
43.
  • Wehrspaun, Claudia, et al. (author)
  • Early event-related potentials indicate context-specific target processing for eye and hand motor systems
  • 2013
  • In: Neuroscience Research. - : Elsevier BV. - 0168-0102. ; 77:1-2, s. 50-57
  • Journal article (peer-reviewed)abstract
    • Concurrent eye and hand movements toward a common visual target require different motor programs based on identical visual input. We used event-related brain potentials (ERP) to determine if and when the processing of the visual target differs for the two motor systems. The N2, an index for target evaluation, was more negative for the target of a hand than of an eye movement in two experiments. A possible interpretation for this finding is different visual target processing. Targets for hand movements require a different weighting of visual information, for example concerning features such as surface structure which are important for hand but not for eye movements. In experiment 2, the early C1-component, which had an average maximum at 67 ms following target onset, was significantly more negative when subjects pointed at the stimuli. Traditionally, the C1 has been regarded as a sensory component, but recent studies have linked it to higher order processing, such as attention and expectations. Thus, the present data indicate that target processing for eye or hand movements is already context-specific during early visual information processing. We suggest that differences in a target's relevance for upcoming movements modify target processing as well as sensory expectations.
  •  
44.
  • Di Mauro, A., et al. (author)
  • Development of innovative micro-pattern gaseous detectors with resistive electrodes and first results of their applications
  • 2007
  • In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 581:1-2, s. 225-231
  • Journal article (peer-reviewed)abstract
    • The paper summarizes our latest progress in the development of newly introduced micro-pattern gaseous detectors with resistive electrodes. These resistive electrodes protect the detector and the front-end electronics in case of occasional discharges and thus make the detectors very robust and reliable in operation. As an example, we describe in greater detail a recently developed GEM-like detector, fully spark-protected with electrodes made of resistive kapton. We discovered that all resistive layers used in these studies (including kapton) that are coated with photosensitive layers, such as CsI, can be used as efficient photocathodes for detectors operating in a pulse counting mode. There is a description of the first applications of such detectors combined with CsI or SbCs photocathodes for the detection of UV photons at room and cryogenic temperatures.
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