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- Ajayi, Abiodun, et al.
(författare)
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Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model
- 2012
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Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Spinocerebellar ataxia type 7 (SCA7) is one of nine inherited neurodegenerative disorders caused by polyglutamine (polyQ) expansions. Common mechanisms of disease pathogenesis suggested for polyQ disorders include aggregation of the polyQ protein and induction of oxidative stress. However, the exact mechanism(s) of toxicity is still unclear. Results: In this study we show that expression of polyQ expanded ATXN7 in a novel stable inducible cell model first results in a concomitant increase in ROS levels and aggregation of the disease protein and later cellular toxicity. The increase in ROS could be completely prevented by inhibition of NADPH oxidase (NOX) complexes suggesting that ATXN7 directly or indirectly causes oxidative stress by increasing superoxide anion production from these complexes. Moreover, we could observe that induction of mutant ATXN7 leads to a decrease in the levels of catalase, a key enzyme in detoxifying hydrogen peroxide produced from dismutation of superoxide anions. This could also contribute to the generation of oxidative stress. Most importantly, we found that treatment with a general anti-oxidant or inhibitors of NOX complexes reduced both the aggregation and toxicity of mutant ATXN7. In contrast, ATXN7 aggregation was aggravated by treatments promoting oxidative stress. Conclusion: Our results demonstrates that oxidative stress contributes to ATXN7 aggregation as well as toxicity and show that anti-oxidants or NOX inhibition can ameliorate mutant ATXN7 toxicity.
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- Norberg, Joakim, et al.
(författare)
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Effects of attention manipulations on motivated attention to feared and nonfeared negative distracters in spider fear
- 2013
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Ingår i: BMC Neuroscience. - : Springer Science+Business Media B.V.. - 1471-2202. ; 14:139
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWhen people view emotional and neutral pictures, the emotional pictures capture more attention than do neutral pictures. In support, studies with event-related potentials have shown that the early posterior negativity (EPN) and the late positive potential (LPP) to emotional versus neutral pictures are enhanced when pictures are attended. However, this motivated attention decreases when voluntary attention is directed away from the pictures. Most previous studies included only generally emotional pictures of either negative or positive valence. Because people with spider fear report intense fear of spiders, we examined whether directing attention away from emotional pictures at fixation decreases motivated attention less strongly for spiders than for generally negative distracters.ResultsWe recorded event-related potentials from 128 channels to study whether manipulations of attention (i.e., spatial attention and perceptual load) decrease the EPN and the LPP to emotional distracters less strongly for spiders than for fear-irrelevant negative pictures in people with spider fear. Results confirmed that the EPN and the LPP to spiders (vs. neutral pictures) were particularly enhanced in participants with spider fear compared to participants without spider fear. When attention was directed away from the pictures, the EPN and the LPP to spiders (vs. neutral pictures) decreased similarly in fearful and nonfearful participants. Further, in fearful participants, the decrease in the EPN and the LPP was similar for spiders and for fear-irrelevant negative pictures.ConclusionsOur findings suggest that for people with spider fear, directing attention away from emotional pictures at fixation decreases motivated attention to these distracters similarly for spiders as for fear-irrelevant negative pictures. These findings imply that attention to spiders in spider fear does not exceed the level of attention expected from the spider pictures’ high arousal and negative valence (i.e., their intrinsic motivated attention).
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- Nordström, Henrik, et al.
(författare)
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Emotional event-related potentials are larger to figures than scenes but are similarly reduced by inattention
- 2012
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Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 13, s. 49-
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Tidskriftsartikel (refereegranskat)abstract
- Background: In research on event-related potentials (ERP) to emotional pictures, greater attention to emotional than neutral stimuli (i.e., motivated attention) is commonly indexed by two difference waves between emotional and neutral stimuli: the early posterior negativity (EPN) and the late positive potential (LPP). Evidence suggests that if attention is directed away from the pictures, then the emotional effects on EPN and LPP are eliminated. However, a few studies have found residual, emotional effects on EPN and LPP. In these studies, pictures were shown at fixation, and picture composition was that of simple figures rather than that of complex scenes. Because figures elicit larger LPP than do scenes, figures might capture and hold attention more strongly than do scenes. Here, we showed negative and neutral pictures of figures and scenes and tested first, whether emotional effects are larger to figures than scenes for both EPN and LPP, and second, whether emotional effects on EPN and LPP are reduced less for unattended figures than scenes.Results: Emotional effects on EPN and LPP were larger for figures than scenes. When pictures were unattended, emotional effects on EPN increased for scenes but tended to decrease for figures, whereas emotional effects on LPP decreased similarly for figures and scenes.Conclusions: Emotional effects on EPN and LPP were larger for figures than scenes, but these effects did not resist manipulations of attention more strongly for figures than scenes. These findings imply that the emotional content captures attention more strongly for figures than scenes, but that the emotional content does not hold attention more strongly for figures than scenes.
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- Nässel, Dick, et al.
(författare)
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A large population of diverse neurons in the Drosophila central nervous system expresses short neuropeptide F, suggesting multiple distributed peptide functions
- 2008
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Ingår i: BMC Neuroscience. - : Biomed Central. - 1471-2202. ; 9:1, s. 90-125
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Tidskriftsartikel (refereegranskat)abstract
- Background Insect neuropeptides are distributed in stereotypic sets of neurons that commonly constitute a small fraction of the total number of neurons. However, some neuropeptide genes are expressed in larger numbers of neurons of diverse types suggesting that they are involved in a greater diversity of functions. One of these widely expressed genes, snpf, encodes the precursor of short neuropeptide F (sNPF). To unravel possible functional diversity we have mapped the distribution of transcript of the snpf gene and its peptide products in the central nervous system (CNS) of Drosophila in relation to other neuronal markers. Results There are several hundreds of neurons in the larval CNS and several thousands in the adult Drosophila brain expressing snpf transcript and sNPF peptide. Most of these neurons are intrinsic interneurons of the mushroom bodies. Additionally, sNPF is expressed in numerous small interneurons of the CNS, olfactory receptor neurons (ORNs) of the antennae, and in a small set of possibly neurosecretory cells innervating the corpora cardiaca and aorta. A sNPF-Gal4 line confirms most of the expression pattern. None of the sNPF immunoreactive neurons co-express a marker for the transcription factor DIMMED, suggesting that the majority are not neurosecretory cells or large interneurons involved in episodic bulk transmission. Instead a portion of the sNPF producing neurons co-express markers for classical neurotransmitters such as acetylcholine, GABA and glutamate, suggesting that sNPF is a co-transmitter or local neuromodulator in ORNs and many interneurons. Interestingly, sNPF is coexpressed both with presumed excitatory and inhibitory neurotransmitters. A few sNPF expressing neurons in the brain colocalize the peptide corazonin and a pair of dorsal neurons in the first abdominal neuromere coexpresses sNPF and insulin-like peptide 7 (ILP7). Conclusion It is likely that sNPF has multiple functions as neurohormone as well as local neuromodulator/co-transmitter in various CNS circuits, including olfactory circuits both at the level of the first synapse and at the mushroom body output level. Some of the sNPF immunoreactive axons terminate in close proximity to neurosecretory cells producing ILPs and adipokinetic hormone, indicating that sNPF also might regulate hormone production or release.
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