| 1. |
- Konradi, C, et al.
(författare)
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Transcriptome analysis in a rat model of L-DOPA-induced dyskinesia
- 2004
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 17:2, s. 219-236
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Tidskriftsartikel (refereegranskat)abstract
- We have examined the pattern of striatal messenger RNA expression of over 8000 genes in a rat model of levodopa (L-DOPA)-induced dyskinesia and Parkinson disease (PD). 6-Hydroxydopamine (6-OHDA)-lesioned rats were treated with L-DOPA or physiological saline for 22 days and repeatedly tested for antiakinetic response to L-DOPA and the development of abnormal involuntary movements (AIMs). In a comparison of rats that developed a dyskinetic motor response to rats that did not, we found striking differences in gene expression patterns. In rats that developed dyskinesia, GABA neurons had an increased transcriptional activity, and genes involved in Ca2+ homeostasis, in Ca2+-dependent signaling, and in structural and synaptic plasticity were upregulated. The gene expression patterns implied that the dyskinetic striatum had increased transcriptional, as well as synaptic activity, and decreased capacity for energy production. Some basic maintenance chores such as ribosome protein biosynthesis were downregulated, possibly a response to expended of ATP levels. (C) 2004 Elsevier Inc. All rights reserved.
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| 2. |
- Kuter, Katarzyna Z., et al.
(författare)
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The role of glia in Parkinson's disease : Emerging concepts and therapeutic applications
- 2020
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Ingår i: Recent Advances in Parkinson's Disease. - : Elsevier. - 0079-6123 .- 1875-7855. - 9780444642608 ; 252, s. 131-168
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Bokkapitel (refereegranskat)abstract
- Originally believed to primarily affect neurons, Parkinson's disease (PD) has recently been recognized to also affect the functions and integrity of microglia and astroglia, two cell categories of fundamental importance to brain tissue homeostasis, defense, and repair. Both a loss of glial supportive-defensive functions and a toxic gain of glial functions are implicated in the neurodegenerative process. Moreover, the chronic treatment with L-DOPA may cause maladaptive glial plasticity favoring a development of therapy complications. This chapter focuses on the pathophysiology of PD from a glial point of view, presenting this rapidly growing field from the first discoveries made to the most recent developments. We report and compare histopathological and molecular findings from experimental models of PD and human studies. We moreover discuss the important role played by astrocytes in compensatory adaptations taking place during presymptomatic disease stages. We finally describe examples of potential therapeutic applications stemming from an increased understanding of the important roles of glia in PD.
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