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- Bonde, Sara
(författare)
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Death, survival, and morphological development of hippocampal granule cells born in an inflammatory environment
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The brain continues to form new neurons throughout life. This process of adult neurogenesis has been thoroughly documented in several species including birds, rodents and humans. Adult neurogenesis is not a global process, but is confined to two subcompartments of the brain; the subventricular zone lining the lateral ventricles, and the subgranular zone (SGZ) in the hippocampal formation. A variety of stimuli such as voluntary exercise, epileptic seizure activity and inflammation can affect the basal level of neurogenesis. In the course of pathological conditions such as Alzheimer’s disease, multiple sclerosis, epilepsy and stroke, an inflammatory response is initiated in the brain. Prolonged epileptic seizure activity, status epilepticus (SE), strongly imposes on the integrity of the delicate brain structure and cell communication. SE not only induces inflammation, but also neuronal death and a transient increase of basal adult neurogenesis in the hippocampal formation. What role inflammation plays in a disease such as epilepsy, and how it affects the neurons born in the aftermath of seizure activity, is largely unknown. The specific aim of the four studies included in this thesis was to investigate the effect inflammation has on the amount of basal and seizure-induced neurogenesis, and if the morphological development or functional characteristics of new neurons is affected when the neuron is born into an inflammatory environment. In brief, the purpose was to investigate the quantity and quality of the neurogenic outcome in inflammation. To comprehend the interplay between neurogenesis and inflammation would provide a valuable insight into disease progression, and could ultimately be part of the treatment or even a cure for pathological conditions involving seizure activity and inflammation.
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| 2. |
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| 3. |
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| 4. |
- Ekdahl Clementson, Christine, et al.
(författare)
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Inflammation is detrimental for neurogenesis in adult brain.
- 2003
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 100:23, s. 13632-13637
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Tidskriftsartikel (refereegranskat)abstract
- New hippocampal neurons are continuously generated in the adult brain. Here, we demonstrate that lipopolysaccharide-induced inflammation, which gives rise to microglia activation in the area where the new neurons are born, strongly impairs basal hippocampal neurogenesis in rats. The increased neurogenesis triggered by a brain insult is also attenuated if it is associated with microglia activation caused by tissue damage or lipopolysaccharide infusion. The impaired neurogenesis in inflammation is restored by systemic administration of minocycline, which inhibits microglia activation. Our data raise the possibility that suppression of hippocampal neurogenesis by activated microglia contributes to cognitive dysfunction in aging, dementia, epilepsy, and other conditions leading to brain inflammation.
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| 6. |
- Jakubs, Katherine, et al.
(författare)
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Environment Matters: Synaptic Properties of Neurons Born in the Epileptic Adult Brain Develop to Reduce Excitability.
- 2006
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273. ; 52:6, s. 1047-1059
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Tidskriftsartikel (refereegranskat)abstract
- Neural progenitors in the adult dentate gyrus continuously produce new functional granule cells. Here we used whole-cell patch-clamp recordings to explore whether a pathological environment influences synaptic properties of new granule cells labeled with a GFP-retroviral vector. Rats were exposed to a physiological stimulus, i.e., running, or a brain insult, i.e., status epilepticus, which gave rise to neuronal death, inflammation, and chronic seizures. Granule cells formed after these stimuli exhibited similar intrinsic membrane properties. However, the new neurons born into the pathological environment differed with respect to synaptic drive and short-term plasticity of both excitatory and inhibitory afferents. The new granule cells formed in the epileptic brain exhibited functional connectivity consistent with reduced excitability. We demonstrate a high degree of plasticity in synaptic inputs to adult-born new neurons, which could act to mitigate pathological brain function.
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| 7. |
- Jakubs, Katherine, et al.
(författare)
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Inflammation regulates functional integration of neurons born in adult brain.
- 2008
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Ingår i: The Journal of Neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 28:47, s. 12477-12488
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation influences several steps of adult neurogenesis, but whether it regulates the functional integration of the new neurons is unknown. Here, we explored, using confocal microscopy and whole-cell patch-clamp recordings, whether a chronic inflammatory environment affects the morphological and electrophysiological properties of new dentate gyrus granule cells, labeled with a retroviral vector encoding green fluorescent protein. Rats were exposed to intrahippocampal injection of lipopolysaccharide, which gave rise to long-lasting microglia activation. Inflammation caused no changes in intrinsic membrane properties, location, dendritic arborization, or spine density and morphology of the new cells. Excitatory synaptic drive increased to the same extent in new and mature cells in the inflammatory environment, suggesting increased network activity in hippocampal neural circuitries of lipopolysaccharide-treated animals. In contrast, inhibitory synaptic drive was more enhanced by inflammation in the new cells. Also, larger clusters of the postsynaptic GABA(A) receptor scaffolding protein gephyrin were found on dendrites of new cells born in the inflammatory environment. We demonstrate for the first time that inflammation influences the functional integration of adult-born hippocampal neurons. Our data indicate a high degree of synaptic plasticity of the new neurons in the inflammatory environment, which enables them to respond to the increase in excitatory input with a compensatory upregulation of activity and efficacy at their afferent inhibitory synapses.
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| 8. |
- Van Meerbergen, Sara, 1981-
(författare)
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Nederländska bilderböcker blir svenska : En multimodal översättningsanalys
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis considers the translation of Dutch and Flemish picture books into Swedish from 1995 to 2006. The main aim of the thesis is to study what meaning the notion translation takes on where picture books are concerned and how the translation practice for picture books is influenced by international co-productions. The thesis includes a bibliographical study and a larger case study of the Dutch picture book artist Dick Bruna and his internationally renowned picture books about the rabbit Miffy in Swedish translation.Working within the theoretical frame of descriptive translation studies (DTS), I describe and analyse picture book translation as a phenomenon and a practice that occurs at a certain moment in time in a certain sociocultural context. Using the model of Toury (1995), I study translation norms governing the selection and translation of Dutch and Flemish picture books and of Bruna’s picture books about Miffy in particular. Toury’s model is largely designed for the analysis of written texts. As picture book texts combine both verbal and visual modes of expression, I use multimodal analysis combining the social semiotic visual grammar of Kress & van Leeuwen (2006) with systemic functional linguistics (SFL) as a tool to analyse the translation of picture book texts. By combining DTS and SFL, I study translation as a cultural and social semiotic practice.The analyses in the thesis indicate that picture book translation can be characterised as an international, target culture-oriented and multimodal translation practice. The multimodal translation analysis shows that, while translated picture books have the same images as their source text due to co-production, images can be combined with different social meanings, as for instance images of children and interaction with the reader, expressed in the written text. Images can also assume different meaning potentials and also referential interplay and plausible reading paths between words and images can change.
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