| 1. |
- Lindquist, Catarina, et al.
(författare)
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Extrasynaptic GABA(A) channels activated by THIP are modulated by diazepam in CA1 pyramidal neurons in the rat brain hippocampal slice
- 2003
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Ingår i: Molecular and Cellular Neuroscience. - 1044-7431 .- 1095-9327. ; 24:1, s. 250-257
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Tidskriftsartikel (refereegranskat)abstract
- Single-channel currents were activated by THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) in cell-attached patches on CA1 pyramidal neurons in the rat hippocampal slice preparation. THIP activated GABA(A) channels after a delay that was concentration-dependent and decreased by 1 muM diazepam. The currents showed outward rectification. Channels activated at depolarized 40 mV relative to the chloride reversal potential had low conductance (<40 pS) but the conductance increased with time, resulting in high-conductance channels (>40 pS). The average maximal-channel conductances for 2 and 100 muM THIP were 59 and 62 pS (-Vp = 40 mV), respectively, whereas in 2 muM THIP plus 1 muM diazepam, it was 71 pS. The results show that in hippocampal neurons THIP activates channels with characteristics similar to those of channels activated by low concentrations (0.5-5 AM) of GABA. The increase in the inhibitory conductance with membrane depolarization permits gradation of the shunt pathway relative to the level of the excitatory input. (C) 2003 Elsevier Science (USA). All rights reserved.
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| 2. |
- Parmar, Malin, et al.
(författare)
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A transplantation study of expanded human embryonic forebrain precursors: evidence for selection of a specific progenitor population
- 2003
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier. - 1044-7431 .- 1095-9327. ; 23:4, s. 531-543
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Tidskriftsartikel (refereegranskat)abstract
- Neural stem and progenitor cells can be expanded under growth factor stimulation in vitro. It is likely that different mitogens and different culturing techniques selectively expand specific subclasses of cells, but this selection has not been well studied. We have expanded human cells isolated from the lateral ganglionic eminence (LGE) of a 10-week-old embryo in the presence of serum and epidermal growth factor. We provide evidence that culturing in this manner favors expansion of cells with characteristics similar to a subpopulation of LGE cells, the olfactory bulb progenitors, as revealed by their expression of Er81 in vitro. After transplantation into neonatal rats, the cells displayed similar properties to endogenous olfactory bulb progenitors when exposed to local cues present in the subventricular zone (SVZ) and rostral migratory stream (RMS). However, the human LGE cells do not migrate or undergo region-specific differentiation when placed outside the SVZ and RMS.
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| 3. |
- Trapp, T, et al.
(författare)
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Transgenic mice overexpressing XIAP in neurons show better outcome after transient cerebral ischemia
- 2003
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Ingår i: Molecular and Cellular Neuroscience. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1044-7431 .- 1095-9327. ; 23:2, s. 302-313
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Tidskriftsartikel (refereegranskat)abstract
- X-chromosome linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis protein (IAP) family and known to inhibit death of various cells under different experimental conditions. Although present in brain tissue, little is known about the physiology of the IAPs in nerve cells. Here we report on the establishment of transgenic mice with overexpression of human XIAP in brain neurons. The mice developed normally, and were more resistant to brain injury caused by transient forebrain ischemia after occlusion of the middle cerebral artery compared to control mice. The XIAP transgenic animals exhibited significantly smaller brain damage, as shown by TUNEL labelling, less reduction in brain protein synthesis, and less active caspase-3 after ischemia compared with controls. Upregulation of RhoB, which is an early indicator of neurological damage, was markedly reduced in the XIAP-overexpressing mice, which had also a better neurological outcome than control animals. This together with the increase in XIAP in normal mouse brain in regions surviving the infarct demonstrates that XIAP is an important factor promoting neuronal survival after ischemia. The results suggest that interference with the levels and the activity of XIAP in neurons may provide targets for the development of drugs limiting neuronal death after ischemia, and possibly in other brain injuries. (C) 2003 Elsevier Science (USA). All rights reserved.
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| 4. |
- Yu, L Y, et al.
(författare)
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Regulation of sympathetic neuron and neuroblastoma cell death by XIAP and its association with proteasomes in neural cells
- 2003
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Ingår i: Molecular and Cellular Neuroscience. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1044-7431 .- 1095-9327. ; 22:3, s. 308-318
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Tidskriftsartikel (refereegranskat)abstract
- XIAP (X chromosome-linked inhibitor of apoptosis protein) has been shown to inhibit cell death in a variety of cells. XIAP binds to active caspases, but XIAP also has a carboxy-terminal RING domain that can regulate cell death via protein degradation. Here we have studied the function of full-length and RING-deleted XIAP in mouse sympathetic neurons microinjected with expression plasmids and in neuroblastoma cells stably overexpressing these proteins. Both full-length and RING-deleted XIAP-protected sympathetic neurons against death induced by nerve growth factor (NGF) withdrawal to about the same extent. However, the two proteins were differentially localized in transfected neurons, with RING-deleted XIAP present in the cytoplasm and full-length XIAP found mostly in cytoplasmic protein aggregates, as revealed by transmission electron microscopy. The occurrence of these aggregates was blocked by lactacystin, a proteasome inhibitor. In neuroblastoma cells, RING-deleted XIAP protected against death induced by staurosporine, thapsigargin, or serum withdrawal, whereas full-length XIAP was without effect. Full-length, but not RING-deleted, XIAP was degraded and ubiquitinated in the neuroblastoma cells. The results show that the presence of the RING domain differentially affected the neuroprotective ability of XIAP in sensory neurons and neuroblastoma cells. The RING domain was essentially required for the proteasomal association of XIAP and for its ubiquitination. (C) 2003 Elsevier Science (USA). All rights reserved.
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| 5. |
- Althini, Susanna, et al.
(författare)
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Blocked MAP kinase activity selectively enhances neurotrophic growth responses
- 2004
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431 .- 1095-9327. ; 25:2, s. 345-354
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Tidskriftsartikel (refereegranskat)abstract
- Bone morphogenetic proteins (BMPs) 4 and 6 as well as MEK inhibitors PD98059 and U0126 potentiate neurotrophin 3 (NT3)- and neurturin (NTN)-induced neurite outgrowth and survival of peripheral neurons from the E9 chicken embryo. Preexposure to BMP4 or PD98059 was sufficient to prime the potentiation of subsequently added NT3. Phosphorylation of Erk2, induced by NT3, was reduced by MEK inhibition but unaffected by BMP signaling. Real-time PCR showed that neither BMP stimulation nor MEK inhibition increased Trk receptor expression and that the BMP-induced genes Smad6 and Id1 were not upregulated by PD98059. In contrast, both MEK inhibition and BMP signaling suppressed transcription of the serum-response element (SRE)-driven Egr1 gene. A reporter assay using NGF-stimulated PC12 cells demonstrated that MEK/Erk/Elk-driven transcriptional activity was inhibited by Smad1/5 and by PD98059. Thus, suppression of SRE-controlled transcription represents a likely convergence point for pathways regulating neurotrophic responses.
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| 6. |
- Andrae, Johanna, et al.
(författare)
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Platelet-derived growth factor receptor-alpha in ventricular zone cells and in developing neurons.
- 2001
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431 .- 1095-9327. ; 17:6
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Tidskriftsartikel (refereegranskat)abstract
- Cells in the early neuroepithelium differentiate and give rise to all cells in the central nervous system (CNS). The ways from a multipotent CNS stem cell to specialized neurons and glia are not fully understood. Using immunohistochemistry we found that neuroepithelial cells express the platelet-derived growth factor receptor-alpha (PDGFR-alpha) in the neural plate at embryonic day 8.5 and onwards in the neural tube. The protein was polarized to ventricular endfeet. Furthermore, PDGFR-alpha expression was localized to cells undergoing early neuronal development. We also found PDGFR-alpha expression in developing granule cells in the postnatal cerebellum, in Purkinje cells in the adult cerebellum and on processes of developing dorsal root ganglion cells. Previous reports mainly describe PDGFR-alpha expression in oligodendrocyte precursors and glial cells. We believe, in line with a few previous reports, that the PDGFR-alpha in addition marks a pool of undifferentiated cells, which are able to differentiate into neurons.
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| 7. |
- Brannvall, K, et al.
(författare)
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Estrogen-receptor-dependent regulation of neural stem cell proliferation and differentiation
- 2002
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Ingår i: Molecular and Cellular Neuroscience. - Uppsala Univ, Ctr Biomed, Dept Neurosci, S-75123 Uppsala, Sweden. : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1044-7431 .- 1095-9327. ; 21:3, s. 512-520
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen has profound effects on function and plasticity of the nervous system. Receptors for estrogen (ERs) are expressed by neurons in several areas of the brain. Here we demonstrate that embryonic and adult rat neural stem cells (NSC) express ERalpha and ERbeta, 17beta-Estradiol treatment decreased the proliferation of NSC stimulated by epidermal growth factor (EGF), which was due to the upregulation of the cyclin-dependent kinase (CDK) inhibitor, p21(Cip1). The modulatory effect of 17beta-estradiol on EGF was more pronounced in adult NSC. However, 17beta-estradiol alone increased the proliferation of embryonic, but not adult, NSC. The effect of 17beta-estradiol was inhibited by the ER antagonist, ICI-182780, showing an involvement of ERs. 17beta-Estradiol also increased the ratio of neurons to glia cells in embryonic NSC, but not in adult NSC, suggesting an influence on neurogenesis during embryonic development. The data show that estrogen, via ER, affects the proliferation and differentiation of NSC cells, probably acting in conjunction with other factors governing NSC development.
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| 8. |
- Korhonen, Laura, 1974-, et al.
(författare)
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Regulation of X-chromosome-linked inhibitor of apoptosis protein in kainic acid-induced neuronal death in the rat hippocampus
- 2001
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Ingår i: Molecular and Cellular Neuroscience. - Uppsala Univ, Ctr Biomed, Dept Neurosci, S-75123 Uppsala, Sweden. Univ Palermo, Fac Med, Inst Human Physiol, I-95125 Palermo, Italy. : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1044-7431 .- 1095-9327. ; 17:2, s. 364-372
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Tidskriftsartikel (refereegranskat)abstract
- XIAP (X-chromosome-linked inhibitor of apoptosis protein) is an antiapoptotic protein which inhibits the activity of caspases and suppresses cell death. However, little is known about the presence and function of XIAP in the nervous system. Here we report that XIAP mRNA is expressed in developing and adult rat brain. Using a specific antibody, we observed XIAP-immunoreactive cells in different brain regions, among others, in the hippocampus and cerebral cortex. Kainic acid, which induces delayed cell death of specific neurons, increased the levels of XIAP in the CA3 region of hippocampus. XIAP was, however, largely absent in cells undergoing cell death, as shown by TUNEL labeling and staining for active caspase-3. In cultured hippocampal neurons, XIAP was initially upregulated by kainic acid and then degraded in a process blocked by the caspase-3 inhibitor DEVD. Similarly, recombinant XIAP is cleaved by active caspase-3 in vitro. The results show that there is biphasic regulation of XIAP in the hippocampus following kainic acid and that XIAP becomes a target for caspase-3 activated during cell death in the hippocampus. The degradation of XIAP by kainic acid contributes to neuronal cell death observed in vulnerable neurons of the hippocampus after caspase activation.
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| 9. |
- Norlin, Marianne E., et al.
(författare)
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Spatially restricted expression of regulators of G-protein signaling in primary olfactory neurons.
- 2001
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431 .- 1095-9327. ; 17:5, s. 872-82
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Tidskriftsartikel (refereegranskat)abstract
- The intracellular signal transduction machinery of heterotrimeric G-protein coupled odorant and putative pheromone receptors converts odorous information into a cellular response. We have investigated for the presence of 18 members of the family termed "regulators of G-protein signaling" (RGS) in primary olfactory sensory neurons of the main as well as the accessory (vomeronasal) system of the mouse. Unexpectedly, expression of a few RGS members show spatial restrictions correlating with the patterns described for G-protein coupled receptors in these two types of olfactory neurons. RGS3 was selectively coexpressed with the Galphai2 G-protein subunit in a subpopulation of vomeronasal neurons. The mutually exclusive spatial extents of RGS9 and RGSZ1 expression in main olfactory neurons corresponded precisely to that of certain odorant receptor zones. This renders these RGS members the first described intracellular signal transduction components with a potential role in the spatially organized sensory coding in the main olfactory system.
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| 10. |
- Norlin, Marianne, et al.
(författare)
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Evidence for gradients of gene expression correlating with zonal topography of the olfactory sensory map
- 2001
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Ingår i: Molecular and Cellular Neuroscience. - : Academic Press. - 1044-7431 .- 1095-9327. ; 18:3, s. 283-295
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Tidskriftsartikel (refereegranskat)abstract
- Signals regulating diversification of olfactory sensory neurons to express odorant receptors and other genes necessary for correct assembly of the olfactory sensory map persist in the olfactory epithelium of adult mouse. We have screened for genes with an expression pattern correlating with the topography odorant receptor-expression zones. The Msx1 homeobox gene and a semaphorin receptor (Neuropilin-2) showed graded expression patterns in the olfactory epithelium. The gradients of Msx1 and Neuropilin-2 expression in basal cells and neurons, respectively, correlated with expression of a retinoic acid-synthesizing enzyme (RALDH2) in lamina propria. A BMP-type I receptor (Alk6) showed a reverse gradient of expression in the supporting cells of the epithelium. Considering known functions of identified genes in cell specification and axon guidance this suggests that zonal division of the olfactory sensory map is maintained, during continuous neurogenesis, as a consequence of topographic counter gradients of positional information.
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