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  • 1.
    Andin, Josefine
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics.
    Hallbeck, Martin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Mohammed, Abdul H
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Influence of environmental enrichment on steady-state mRNA levels for EAAC1, AMPA1 and NMDA2A receptor subunits in rat hippocampus2007In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1174, no 1, p. 18-27Article in journal (Refereed)
    Abstract [en]

    Interaction with the environment has a key role in refining the neuronal circuitry required for normal brain function throughout life. Profound effects of enriched environment have been shown on neuronal structure and chemistry in experimental animals. Epidemiological studies imply that this is true also in man, thus cognitive stimulation has a protective effect on neurodegeneration, e.g., in Alzheimer's disease. Glutamatergic pathways are imperative for cognitive functions, such as memory, learning and long-term potentiation, and relies on the AMPA and NMDA glutamate receptors and the hippocampus, with its specific subregions, is an important anatomical substrate in this. The glutamate signalling is also dependent on a fine-tuned transport system, in the hippocampus primarily achieved by the glutamate transporter EAAC1. In this study we show how environmental enrichment modulates these parts of the glutamatergic system using quantitative in situ hybridisation. This work demonstrates for the first time that environmental enrichment modulates the mRNA expression of EAAC1 which is significantly and region specifically decreased in the hippocampus. We also provide evidence for regional and hemisphere-specific upregulation of NMDA mRNA in the hippocampus after environmental enrichment. The current work also shows that AMPA mRNA of the hippocampus is not per se changed by environmental enrichment in adult animals. Taken together, our results extend the knowledge of the glutamatergic system of specific regions of the hippocampus and its modulation by environmental enrichment and could contribute to the development of strategies aimed at limiting pathological changes associated with glutamatergic dysfunctions. © 2007.

  • 2. Arnelo, Urban
    et al.
    Herrington, Margery
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Adrian, Thomas
    Reidelberger, Roger
    Larsson, Jörgen
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Strömmer, Lisa
    Ding, Xianzhong
    Permert, Johan
    Effects of long-term infusion of anorexic concentrations of islet amyloid polypeptide on neurotransmitters and neuropeptides in rat brain.2000In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 887, p. 391-398Article in journal (Refereed)
  • 3.
    Bagheri, Maryam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Roghani, Mehrdad
    Shahed University.
    Joghataei, Mohammad-Taghi
    Tehran University of Medical Sciences.
    Mohseni, Simin
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Genistein inhibits aggregation of exogenous amyloid-beta(1-40) and alleviates astrogliosis in the hippocampus of rats2012In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1429, p. 145-154Article in journal (Refereed)
    Abstract [en]

    We addressed the question of whether injection of Amyloid beta (Aβ)(1-40) in the rat brain is associated with pathology in the hippocampus, and if genistein has any protective effect against the neuronal damage caused by Aβ(1-40). Genistein is a plant-derived compound with a structure similar to that of the female sex hormone estrogen and it was recently shown that pretreatment with a single dose of genistein ameliorated learning and memory deficits in an (Aβ)(1-40) rat model of Alzheimer's disease. Here, we report that injection of the amyloid peptide into the hippocampus of rats led to formation of Aβ(1-40) positive aggregates close to the lateral blade of the dentate gyrus (DGlb). We also observed the following in the hippocampus: extensive cell death in the DGlb (P<0.0001), CA1 (P=0.03), and CA3 (P=0.002); an increased number of iNOS-expressing cells (P=0.01) and gliosis. Genistein given to rats by gavage 1h before injection of Aβ(1-40) inhibited the formation of Aβ(1-40) positive aggregates in the brain tissue and led to increased number of nNOS(+) (P=0.0001) cells in the hippocampus compared to sham-operated genistein-treated controls. Treatment with genistein also alleviated the extensive astrogliosis that occurred in Aβ(1-40)-injected hippocampus to a level similar to that observed in sham-operated rats. We conclude that the neurons in the DGlb are most sensitive to Aβ(1-40), and a single dose of genistein can ameliorate Aβ(1-40) induced pathology.

  • 4.
    Bergamino, Maurizio
    et al.
    Laureate Institute for Brain Research, Tulsa, OK, USA.
    Farmer, Madison
    Roosevelt University, Department of Industrial and Organizational Psychology, Chicago, IL, USA.
    Yeh, Hung-Wen
    Laureate Institute for Brain Research, Tulsa, OK, USA.
    Paul, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Hamilton, Paul J.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Statistical differences in the white matter tracts in subjects with depression by using different skeletonized voxel-wise analysis approaches and DTI fitting procedures2017In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1669, p. 131-140Article in journal (Refereed)
    Abstract [en]

    Major depressive disorder (MDD) is one of the most significant contributors to the global burden of illness. Diffusion tensor imaging (DTI) is a procedure that has been used in several studies to characterize abnormalities in white matter (WM) microstructural integrity in MDD. These studies, however, have provided divergent findings, potentially due to the large variety of methodological alternatives available in conducting DTI research. In order to determine the importance of different approaches to coregistration of DTI-derived metrics to a standard space, we compared results from two different skeletonized voxel-wise analysis approaches: the standard TBBS pipeline and the Advanced Normalization Tools (ANTs) approach incorporating a symmetric image normalization (SyN) algorithm and a group-wise template (ANTs TBSS). We also assessed effects of applying twelve different fitting procedures for the diffusion tensor. For our dataset, lower fractional anisotropy (FA) and axial diffusivity (AD) in depressed subjects compared with healthy controls were found for both methods and for all fitting procedures. No group differences were found for radial and mean diffusivity indices. Importantly, for the AD metric, the normalization methods and fitting procedures showed reliable differences, both in the volume and in the number of significant between-groups difference clusters detected. Additionally, a significant voxel-based correlation, in the left inferior fronto-occipital fasciculus, between AD and self-reported stress was found only for one of the normalization procedure (ANTs TBSS). In conclusion, the sensitivity to detect group-level effects on DTI metrics might depend on the DTI normalization and/or tensor fitting procedures used.

  • 5.
    Bjartmar, Lisa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences.
    Alkhori, Liza
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ruud, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Geriatric Medicine.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Cytology.
    Long-term treatment with antidepressants, but not environmental stimulation, induces expression of NP2 mRNA in hippocampus and medial habenula2010In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1328, p. 24-33Article in journal (Refereed)
    Abstract [en]

    Neuronal Pentraxin 2 (NP2, Narp), known to mediate clustering of glutamatergic AMPA receptors at synapses, is involved in activity-dependent synaptogenesis and synaptic plasticity. In experimental settings, antidepressant treatment as well as a stimulating environment has a positive influence on cognition and hippocampal plasticity. This study demonstrates that NP2 mRNA is robustly expressed in the hippocampus and the medial habenula (MHb), both regions implicated in cognitive functions. Furthermore, NP2 mRNA expression is enhanced in the hippocampal subregions as well as in the MHb after long-term treatment with antidepressant drugs of various monoaminergic profiles, indicating a common mode of action of different antidepressant drugs. This effect occurs at the time frame where clinical response is normally achieved. In contrast, neither environmental enrichment nor deprivation has any influence on long-term NP2 mRNA expression. These findings support an involvement of NP2 in the pathway of antidepressant induced plasticity, but not EE induced plasticity; that NP2 might constitute a common link for the action of different types of antidepressant drugs and that the MHb could be a putative region for further studies of NP2.

  • 6.
    Dawidson, I
    et al.
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden.
    Blom, M
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden.
    Angmar-Mansson, B
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Lundeberg, T
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden.
    Sensory stimulation (acupuncture) increases the release of CGRP and VIP in the saliva of xerostomic patients1999In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 848, no 1-2, p. P62-Conference paper (Other academic)
  • 7. Eriksson, IS
    et al.
    Allard, P.
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    (3H)tiagabine binding to GABA uptake sites in human brain.1999In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 18, no 1-2, p. 183-188Article in journal (Refereed)
    Abstract [en]

    The binding of [H-3]tiagabine ((RS-1-(4,4-(3-methyl-2-thienyl)-3-butenyl)-3 carboxylic acid) to homogenates of frozen post-mortem human brain has been characterized. Inhibition experiments with gamma-aminobutyric acid (GAB,4), GABA uptake inhibitors, ligands active at postsynaptic GABA receptors and receptors for other neurotransmitters, suggest that [H-3]tiagabine binds with high affinity to GABA uptake sites. Inhibition and kinetic experiments suggests that 70%-80% of the binding is to a high affinity site. Saturation experiments showed that the binding was saturable. B-max was 3.4 pmol/mg protein and K-d 16 nM in frontal cortex. The dissociation constants (K-d) measured in kinetic and equilibrium experiments were in the same range (16-56 nM). The regional distribution was studied in nine brain regions and the binding was heterogenous, with the highest binding in frontal cortex and parietal cortex and the lowest binding in nucleus caudatus and putamen. This is, to our knowledge, the first study on [H-3]tiagabine binding in human tissue. It is concluded that [H-3]tiagabine binding can be used as a specific marker for the GABA transporter GAT-1 in homogenates of human brain.

  • 8.
    Forkstam, Christian
    et al.
    Karolinska Institutet.
    Elwér, Åsa
    Karolinska Institutet.
    Ingvar, Martin
    Karolinska Institutet.
    Petersson, Karl Magnus
    Karolinska Institutet.
    Instruction effects in implicit artificial grammar learning: A preference for grammaticality2008In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1221, no 24, p. 80-92Article in journal (Refereed)
    Abstract [en]

    Human implicit learning can be investigated with implicit artificial grammar learning, a paradigm that has been proposed as a simple model for aspects of natural language acquisition. In the present study we compared the typical yes–no grammaticality classification, with yes–no preference classification. In the case of preference instruction no reference to the underlying generative mechanism (i.e., grammar) is needed and the subjects are therefore completely uninformed about an underlying structure in the acquisition material. In experiment 1, subjects engaged in a short-term memory task using only grammatical strings without performance feedback for 5 days. As a result of the 5 acquisition days, classification performance was independent of instruction type and both the preference and the grammaticality group acquired relevant knowledge of the underlying generative mechanism to a similar degree. Changing the grammatical stings to random strings in the acquisition material (experiment 2) resulted in classification being driven by local substring familiarity. Contrasting repeated vs. non-repeated preference classification (experiment 3) showed that the effect of local substring familiarity decreases with repeated classification. This was not the case for repeated grammaticality classifications. We conclude that classification performance is largely independent of instruction type and that forced-choice preference classification is equivalent to the typical grammaticality classification.

  • 9.
    Hilke, Susanne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Hokfelt, T.
    Hökfelt, T., Department of Neuroscience, Karolinska Institutet, Retzius väg 8, SE-171 77 Stockholm, Sweden.
    Darwish, M.
    Faculty of Veterinary Medicine, Department of Animal Hygiene, Assuit University, Egypt.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Cholecystokinin levels in the rat brain during the estrous cycle2007In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1144, no 1, p. 70-73Article in journal (Refereed)
    Abstract [en]

    Cholecystokinin (CCK) is widely distributed in the brain, and its expression has been shown to be regulated by estrogen. In the present study we used radioimmunoassay to monitor CCK levels in rat brain during a normal estrous cycle. Compared to di-estrous and estrous, CCK-like immunoreactivity was significantly reduced in cingulate and frontal cortex, hippocampus, striatum and hypothalamus during pro-estrous, that is the phase with the highest plasma estradiol levels. These results provide further evidence that circulating steroid hormones in the female rat can influence expression of a brain peptide, in this case CCK, and primarily in the limbic system, which is interesting in the context that CCK has been associated with anxiety and depression in both animals and humans. © 2007 Elsevier B.V. All rights reserved.

  • 10.
    Kaiser, Andreas
    et al.
    Karolinska University Hospital, Sweden .
    Kale, Ajay
    Karolinska University Hospital, Sweden .
    Novozhilova, Ekaterina
    Karolinska University Hospital, Sweden .
    Siratirakun, Piyaporn
    Karolinska University Hospital, Sweden .
    Aquino, Jorge B.
    Karolinska Institute, Sweden .
    Thonabulsombat, Charoensri
    Mahidol University, Thailand .
    Ernfors, Patrilz
    Karolinska Institute, Sweden .
    Olivius, Petri
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Brain stern slice conditioned medium contains endogenous BDNF and GDNF that affect neural crest boundary cap cells in co-culture2014In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1566, p. 12-23Article in journal (Refereed)
    Abstract [en]

    Conditioned medium (CM), made by collecting medium after a few days in cell culture and then re-using it to further stimulate other cells, is a known experimental concept since the 1950s. Our group has explored this technique to stimulate the performance of cells in culture in general, and to evaluate stem- and progenitor cell aptitude for auditory nerve repair enhancement in particular. As compared to other mediums, all primary endpoints in our published experimental settings have weighed in favor of conditioned culture medium, where we have shown that conditioned culture medium has a stimulatory effect on cell survival. In order to explore the reasons for this improved survival we set out to analyze the conditioned culture medium. We utilized ELISA kits to investigate whether brain stem (BS) slice CM contains any significant amounts of brain-derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF). We further looked for a donor cell with progenitor characteristics that would be receptive to BDNF and GDNF. We chose the well-documented boundary cap (BC) progenitor cells to be tested in our in vitro co-culture setting together with cochlear nucleus (CN) of the BS. The results show that BS CM contains BDNF and GDNF and that survival of BC cells, as well as BC cell differentiation into neurons, were enhanced when BS CM were used. Altogether, we conclude that BC cells transplanted into a BDNF and GDNF rich environment could be suitable for treatment of a traumatized or degenerated auditory nerve.

  • 11.
    Magnusson, Anna K.
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Eriksson, Birgitta
    Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Tham, Richard
    Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Effects of the GABA agonists baclofen and THIP on long-term compensation in hemilabyrinthectomised rats1998In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 795, no 1-2, p. 307-311Article in journal (Refereed)
    Abstract [en]

    Horizontal eye movements, elicited by sinusoidal rotation in darkness, were recorded with a magnetic search coil technique in pigmented rats, hemilabyrinthectomised 8–12 weeks before the investigation. Separate gains during rotation towards the lesioned side (LS) and the intact side (IS) were calculated by a computer program, demonstrating an asymmetry. Systemic single administration of the GABAB agonist baclofen caused a dose-related temporary rebalancing of the compensatory eye movements to the LS and the IS. At an optimal dose of 14 μmol/kg b.wt symmetry was achieved by excitation of eye movements during rotation to the LS and depression during rotation to the IS. Administration of the GABAA agonist THIP did not obviously reduce the asymmetry. It is suggested that stimulation of GABAB receptors modifies the tonic imbalance between the bilateral vestibular nuclei and/or the central processing of the input from the peripheral sensory organs.

  • 12.
    Niklasson, Magnus
    et al.
    Östergötlands Läns Landsting.
    Tham, Richard
    Linköping University.
    Larsby, Birgitta
    Linköping University.
    Eriksson, Birgitta
    Linköping University.
    Effects of GABAB activation and inhibition on vestibulo-ocular and optokinetic responses in the pigmented rat1994In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 649, no 1-2, p. 151-158Article in journal (Refereed)
    Abstract [en]

    The effects of the GABAB agonist baclofen and the GABAB antagonist CGP 35348, given separately or simultaneously, on the central vestibular system of pigmented rats have been evaluated. Drugs were administered either intramuscularly or intracerebroventricularly. Eye movements were recorded during vestibular, optokinetic and combined visual-vestibular stimulation. Activation of the GABAB receptors by baclofen caused a dose related disturbance of the system, manifested by (1) a decrease of the optokinetic gain, (2) a reduced ability to suppress nystagmus during conflicting vestibular and visual input, and (3) a disability to maintain the eccentric eye position upon a spontaneous saccade. All these effects could be inhibited in a dose-dependent fashion by CGP 35348, suggesting that the findings are specifically related to the GABAB receptor. Given separately, the antagonist did not affect the mentioned parameters. During horizontal acceleratory/deceleratory stimulation in darkness baclofen caused a biphasic pattern in the dose-response curves. Small amounts of baclofen caused an increase of the gain and of the duration of poststimulatory nystagmus, while high doses had a depressive action on the same parameters. The stimulating effect of baclofen could be inhibited or even reversed by CGP 35348, which has a depressive effect per se, similar to the effects of baclofen given in the upper range of doses.

  • 13. Roslan Sulaiman, M.
    et al.
    Niklasson, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Östergötlands Läns Landsting, RC - Rekonstruktionscentrum, ÖNH - Öron- Näsa- Halskliniken.
    Tham, Richard
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Östergötlands Läns Landsting, RC - Rekonstruktionscentrum, ÖNH - Öron- Näsa- Halskliniken.
    Dutia, MB
    Modulation of vestibular function by nociceptin/orphanin FQ: an in vivo and in vitro study.1999In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 828, p. 74-82Article in journal (Refereed)
  • 14.
    Rugarn, O
    et al.
    Fac Hlth Sci, Dept Obstet & Gynaecol, Linkoping, Sweden Fac Hlth Sci, Dept Neurosurg, Linkoping, Sweden.
    Theodorsson, Annette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Hammar, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Effects of estradiol on regional concentrations of galanin in the rat brain1999In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 848, no 1-2, p. P323-Conference paper (Other academic)
  • 15.
    Strömberg, H
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Svensson, Samuel
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Hermansson, O
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Distribution of CREB-binding protein immunreactivity in the adult rat brain1999In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 818, p. 510-514Article in journal (Refereed)
  • 16.
    Strömberg, H
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Svensson, Samuel
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Hermansson, O
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Distribution of the transcription factor Signal Transducer and Activator of Transcription 3 in the rat central nervous system and dorsal root ganglia2000In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 853, no 1, p. 105-114Article in journal (Refereed)
    Abstract [en]

    Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor that acts as an intracellular signalling molecule after receptor activation by several cytokines, e.g., interleukin-6, leptin and ciliary neurotrophic factor. We have investigated the localization of STAT3 in the rat central nervous system and dorsal root ganglia. Light microscopic immunohistochemistry showed that STAT3-like immunoreactivity (STAT3-LI) was present in the nucleus and cytoplasm of neurons. STAT3-LI was seen both in cell bodies and in proximal and distal dendrites. Many structures involved in motor functions, such as the ventral horn of the spinal cord, the motor cranial nerve nuclei, the red nucleus and the Purkinje cells of the cerebellum showed STAT3-LI. STAT3-LI was also present in many regions involved in autonomic regulation, such as the intermediolateral cell column of the spinal cord, the nucleus of the solitary tract, the dorsal motor nucleus of the vagus nerve, the area postrema, the locus coeruleus, the Barrington's nucleus and the arcuate, the lateral, the dorsomedial, the ventromedial, and the paraventricular hypothalamic nuclei. Other structures showing STAT3-LI were the dorsal root ganglia, the thalamus (the anterodorsal and paraventricular nucleus), the cerebral neocortex (layer 5) and the olfactory bulb. The wide distribution of STAT3-LI in the nervous system is consistent with reports of cytokine actions in the brain, but the present findings further suggest novel roles for STAT3 in mediating influences of cytokines on specific neuronal circuits regulating motor, sensory and autonomic functions.

  • 17.
    Thonabulsombat, Charoensri
    et al.
    Mahidol University, Salaya, Phutthamonthon, Nakorn Pathom, Thailand.
    Johansson, Saga
    King's College London, UK.
    Spenger, Christian
    Karolinska University Hospital, MR Center, Stockholm, Sweden.
    Ulfendahl, Mats
    Karolinska University Hospital, Stockholm, Sweden.
    Olivius, Petri
    Karolinska University Hospital, Stockholm, Sweden.
    Implanted embryonic sensory neurons project axons toward adult auditory brainstem neurons in roller drum and Stoppini co-cultures2007In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1170, p. 48-58Article in journal (Refereed)
    Abstract [en]

    Previously we have shown in vivo the survival, migration and integration of embryonic dorsal root ganglion (DRG) neurons that were grafted into the inner ear and peripheral auditory nervous system. In order to evaluate relevant factors determining integration of sensory neurons further into the central auditory nervous system, complementary in vitro techniques are necessary. The advantages of in vitro systems are that a large number of factors including various grafts and different conditions can be efficiently examined for. Hence, we co-cultured 300 mu m thick postnatal rat brainstem slices containing the cochlear nucleus including the central part of the 8th cranial nerve with mouse embryonic DRG neurons. The organotypic co-cultures were either grown on coverslips using the roller drum method described by Gahwiler or on membranes according to the interface method described by Stoppini. Neurons in the cochlear nucleus were labeled, with DiI. The results demonstrate that (1) brainstem slices survive for up to 5 weeks in culture, and that (2) co-cultures of embryonic sensory neurons and brainstern show a high degree of neuronal survival, and that (3) survival and axonal outgrowth from the implanted embryonic neurons are dependant on the presence of the brainstern slice rather than on exogenous NGF and that (4) implanted embryonic neurons send axons toward neurons in the cochlear nucleus. (c) 2007 Published by Elsevier B.V.

  • 18.
    Voss, Logan J.
    et al.
    Waikato Dist Health Board, New Zealand .
    Gauffin, Emelie
    Linköping University, Faculty of Health Sciences.
    Ringqvist, Alexandra
    Linköping University, Faculty of Health Sciences.
    Sleigh, James W.
    University of Auckland, New Zealand .
    Investigation into the role of gap junction modulation of intracortical connectivity in mouse neocortical brain slices2014In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1553, p. 24-30Article in journal (Refereed)
    Abstract [en]

    General anesthetics are hypothesized to cause unconsciousness by interrupting communication pathways within the cerebral cortex. A correlate of this has been demonstrated in mouse neocortical slices, where anesthetics disrupt the spread of population field potential activity resulting in a "decoupling" of activity recorded across spatial locations within the slice. In this study we investigated whether this decoupling can be explained by gap junction blockade, with a particular focus on the connexin36 (Cx36) subtype. Baseline, coupled seizure-like event (SLE) activity was recorded from two extracellular electrodes in slices perfused with no-magnesium artificial cerebrospinal fluid (aCSF). The connexin36 gap junction blocker mefloquine (25 mu M) failed to decouple SLE activity in wild-type mice (median(range) decoupling rate of 0.70(0.03-3.00)%, not significantly different from controls). Slices from Cx36 knock-out mice exhibited coupled SLE activity under baseline conditions and readily decoupled when exposed to the general anesthetic etomidate. The general gap junction blocker carbenoxolone (CBX, 100 mu M) strongly decoupled SLE activity compared to controls in wild-type mice (2.7(0.1-42.5) % compared to 0.03(0.0-0.5)%, p=0.0001). Taken together, the results show that Cx36 gap junction blockade does not cause decoupling of intracortical population activity, but the involvement of other gap junction subtypes cannot be ruled out.

  • 19.
    Voss, Logan J.
    et al.
    Waikato Dist Health Board, New Zealand .
    Hansson Baas, Cecilia
    Linköping University, Faculty of Health Sciences.
    Hansson, Linnea
    Linköping University, Faculty of Health Sciences.
    Li, Duan
    Yanshan University, Peoples R China .
    Sleigh, James W.
    University of Auckland, New Zealand .
    Investigation into the effect of the general anaesthetic etomidate on local neuronal synchrony in the mouse neocortical slice2013In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1526, p. 65-70Article in journal (Refereed)
    Abstract [en]

    How general anaesthetic drugs cause unconsciousness is a topic of ongoing clinical and scientific interest. It is becoming increasingly apparent that they disrupt cortical information processing, but the effects appear to depend on the spatial scale under investigation. In this study we investigated whether the intravenous anaesthetic etomidate synchronises neuronal activity on a sub-millimetre scale in mouse neocortical slices. In slices generating no-magnesium seizure-like event (SLE) field activity, we analysed the morphology of field potential activity recorded with 50 mu m extracellular electrodes. The analysis was based on the understanding that the amplitude and sheerness of field potential oscillations correlates with the synchrony of the underlying neural activity. When recorded from the region of the slice initiating SLE activity, etomidate consistently increased both population event amplitude (median(range) 85(24-350) to 101(30-427) mu V) and slope 16.6(1.5-106.2) to 20.2(1.7-111.1) mu V/ms (p=0.016 and p=0.0013, respectively). The results are consistent with an increase in neuronal synchrony within the receptive field of the recording electrode, estimated to be a circle diameter of 300 mu m. In conclusion, the neocortical slice preparation supports in vivo data showing that general anaesthetics increase neuronal synchrony on a local scale and provides an ideal model for investigating underlying mechanisms.

  • 20.
    Zhengquan, Yu
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Li, Wei
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Hillman, Jan
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Brunk, Ulf
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Human neuroblastoma (SH-SY5Y) cells are highly sensitive to the lysosomotropic aldehyde 3-aminopropanal2004In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1016, no 2, p. 163-169Article in journal (Refereed)
    Abstract [en]

    3-Aminopropanal (3-AP), a degradation product of polyamines such as spermine, spermidine and putrescine, is a lysosomotropic small aldehyde that causes apoptosis or necrosis of most cells in culture, apparently by inducing moderate or extensive lysosomal rupture, respectively, and secondary mitochondrial changes. Here, using the human neuroblastoma SH-SY5Y cell line, we found simultaneous occurrence of apoptotic and necrotic cell death when cultures were exposed to 3-AP in concentrations that usually are either nontoxic, or only cause apoptosis. At 30 mM, but not at 10 mM, the lysosomotropic base and proton acceptor NH3 completely blocked the toxic effect of 3-AP, proving that 3-AP is lysosomotropic and suggesting that the lysosomal membrane proton pump of neuroblastoma cells is highly effective, creating a lower than normal lysosomal pH and, thus, extensive intralysosomal accumulation of lysosomotropic drugs. A wave of internal oxidative stress, secondary to changes in mitochondrial membrane potential, followed and gave rise to further lysosomal rupture. The preincubation of cells for 24 h with a chain-breaking free radical-scavenger, α-tocopherol, before exposure to 3-AP, significantly delayed both the wave of oxidative stress and the secondary lysosomal rupture, while it did not interfere with the early 3-AP-mediated phase of lysosomal break. Obviously, the reported oxidative stress and apoptosis/necrosis are consequences of lysosomal rupture with ensuing release of lysosomal enzymes resulting in direct/indirect effects on mitochondrial permeability, membrane potential, and electron transport. The induced oxidative stress seems to act as an amplifying loop causing further lysosomal break that can be partially prevented by α-tocopherol. Perhaps secondary brain damage during a critical post injury period can be prevented by the use of drugs that temporarily raise lysosomal pH, inactivate intralysosomal 3-AP, or stabilize lysosomal membranes against oxidative stress.

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