| 1. |
- Apostolova, Galina, et al.
(författare)
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Neurotransmitter phenotype-specific expression changes in developing sympathetic neurons
- 2007
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431 .- 1095-9327. ; 35:3, s. 397-408
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Tidskriftsartikel (refereegranskat)abstract
- During late developmental phases individual sympathetic neurons undergo a switch from noradrenergic to cholinergic neurotransmission. This phenomenon of plasticity depends on target-derived signals in vivo and is triggered by neurotrophic factors in neuronal cultures. To analyze genome-wide expression differences between the two transmitter phenotypes we employed DNA microarrays. RNA expression profiles were obtained from chick paravertebral sympathetic ganglia, treated with neurotrophin 3, glial cell line-derived neurotrophic factor or ciliary neurotrophic factor, all of which stimulate cholinergic differentiation. Results were compared with the effect of nerve growth factor, which functions as a pro-noradrenergic stimulus. The gene set common to all three comparisons defined the noradrenergic and cholinergic synexpression groups. Several functional categories, such as signal transduction, G-protein-coupled signaling, cation transport, neurogenesis and synaptic transmission, were enriched in these groups. Experiments based on the prediction that some of the identified genes play a role in the neurotransmitter switch identified bone morphogenetic protein signaling as an inhibitor of cholinergic differentiation.
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| 2. |
- Azadi, Seifollah, et al.
(författare)
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Up-regulation and increased phosphorylation of protein kinase C (PKC) delta, mu and theta in the degenerating rd1 mouse retina.
- 2006
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431. ; 31:4, s. 759-773
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Tidskriftsartikel (refereegranskat)abstract
- The rd1 mouse serves as a model for inherited photoreceptor degeneration: retinitis pigmentosa. Microarray techniques were employed to compare the transcriptomes of rd1 and congenic wild-type retinas at postnatal day 11, when degenerative processes have started but most photoreceptors are still present. Of the several genes that were differentially expressed, focus was put on those associated with the protein kinase C (PKC) signaling pathway, in particular PKCδ, μ and θ. Microarray identified these as being up-regulated in the rd1 retina, which was confirmed by QRT-PCR. Western blotting and immunostaining, using antibodies against either total or phosphorylated variants of the PKC isoforms, revealed increased expression and phosphorylation of PKCδ, μ and θ in the rd1 retina at the protein level as well. Our results suggest that these PKC isoforms are involved in rd1 degeneration.
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| 6. |
- Elmi, Muna, 1978, et al.
(författare)
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Mechanism of MASH1 induction by ASK1 and ATRA in adult neural progenitors.
- 2007
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Ingår i: Molecular and cellular neurosciences. - : Elsevier BV. - 1044-7431. ; 36:2, s. 248-59
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Tidskriftsartikel (refereegranskat)abstract
- The molecular mechanisms underlying differentiation and lineage commitment in neural stem cells are just beginning to be understood, however the molecules involved in this process and their functions remain largely unknown. Here we studied the effects and downstream signals of apoptosis signal-regulating kinase 1 (ASK1) together with all-trans retinoic acid (ATRA) on neuronal differentiation in adult hippocampus-derived progenitor (AHP) cells. Following ASK1 over-expression and ATRA treatment in AHPs, a larger number of cells differentiated into neurons and the MASH1 promoter became activated. Analyzing downstream effector molecules of ASK1 or ATRA targeting the MASH1 promoter revealed that the myocyte enhancer factor 2C (MEF2C) mediated ASK1 signalling, while activation of Sp1 was involved in ATRA signalling. Chromatin immunoprecipitation assay on the promoter revealed that ASK1 induced binding of MEF2C and Ca(2+)/calmodulin-dependent kinase II to the MASH1 promoter. Taken together, ASK1 and ATRA activate MEF2C and Sp1, respectively, and up-regulate MASH1 protein expression.
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| 7. |
- Errico, Francesco, et al.
(författare)
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The GTP-binding protein Rhes modulates dopamine signalling in striatal medium spiny neurons
- 2008
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431. ; 37:2, s. 335-345
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Tidskriftsartikel (refereegranskat)abstract
- Rhes is a small GTP-binding protein prominently localized in the striatum. Previous findings obtained in cell culture systems demonstrated an involvement of Rhes in cAMP/PKA signalling pathway, at a level proximal to the activation of heterotrimeric G-protein complex. However, its role in the striatum has been, so far, only supposed. Here we studied the involvement of Rhes in dopaminergic signalling, by employing mice with a null mutation in the Rhes gene. We demonstrated that the absence of Rhes modulates cAMP/PKA signalling in both striatopallidal and striatonigral projection neurons by increasing Golf. protein levels and, in turn, influencing motor responses challenged by dopaminergic agonist/antagonist. Interestingly, we also show that Rhes is required for a correct dopamine-mediated GTP binding, a function mainly associated to stimulation of dopamine D2 receptors. Altogether, our results indicate that Rhes is an important modulator of dopaminergic transmission in the striatum.
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| 9. |
- Holm, Pontus, et al.
(författare)
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Loss- and gain-of-function analyses reveal targets of Pax6 in the developing mouse telencephalon.
- 2007
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431 .- 1095-9327. ; 34:1, s. 99-119
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Forskningsöversikt (refereegranskat)abstract
- Appropriate neurogenesis and patterning of the forebrain requires the transcription factor Pax6, yet it is largely unknown how Pax6 exerts its effects at the molecular level. To characterize Pax6-mediated regulation of gene expression during murine forebrain neurogenesis, we performed microarray analysis with tissue from the dorsal Pax6-dependent telencephalon and the ventral Pax6-negative telencephalon at the onset of neurogenesis (E12) and at mid-neurogenesis (E15) in wild-type and Pax6-deficient mutant littermates. In the Pax6-deficient cortex the expression levels of various transcription factors involved in neurogenesis (like Satb2, Nfia, AP-2 gamma, NeuroD6, Ngn2, Tbr2, Bhlhb5) and the retinoic acid signalling molecule Rlbp1 were reduced. Regulation by Pax6 could be confirmed upon electroporation of a Pax6- and a dominant-negative Pax6-containing vector into embryonic cortex. Taken together, our data reveal novel insights into the molecular pathways regulated by Pax6 during cortical neurogenesis. Most intriguingly, this analysis revealed time- and region-specific differences in Pax6-mediated transcription, explaining the specific function of Pax6 at early and later stages of neurogenesis. (c) 2006 Elsevier Inc. All rights reserved.
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| 10. |
- Ishii, Yoko, et al.
(författare)
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Characterization of neuroprogenitor cells expressing the PDGF beta-receptor within the subventricular zone of postnatal mice.
- 2008
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Ingår i: Molecular and cellular neurosciences. - : Elsevier BV. - 1095-9327 .- 1044-7431. ; 37:3, s. 507-18
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Tidskriftsartikel (refereegranskat)abstract
- We report a considerable number of cells in the ventricular and the subventricular zones (SVZ) of newborn mice to stain positive for the PDGF beta-receptor (PDGFRB). Many of them also stained for nestin and/or GFAP but less frequently for the neuroblast marker doublecortin and for the mitotic marker Ki-67. The SVZ of mice with nestin-Cre conditional deletion of PDGFRB expressed the receptor only on blood vessels and was devoid of any morphological abnormality. PDGFRB(-/-) neurospheres showed a higher rate of apoptosis without any significant decrease in proliferation. They demonstrated reduced capacities of migration and neuronal differentiation in response to not only PDGF-BB but also bFGF. Furthermore, the PDGFR kinase inhibitor STI571 blocked the effects of bFGF in control neurosphere cultures. bFGF increased the activity of the PDGFRB promoter as well as the expression and phosphorylation of PDGFRB. These results suggest the presence of the signaling convergence between PDGF and FGF. PDGFRB is needed for survival, and the effects of bFGF in migration and neural differentiation of the cells may be potentiated by induction of PDGFRB.
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