Astrocyte Reactivity and Reactive Astrogliosis: Costs and Benefits

Pekny, Milos; Pekna, Marcela

doi:10.1152/physrev.00041.2013

Cited by 739 publications

(641 citation statements)

References 281 publications

(336 reference statements)

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“…pathological aSyn species has been reported to induce a glial response in vivo (20,36), we investigated the state of the astrocytes by probing for glial fibrillary acidic protein (GFAP). An increase in GFAP levels could only be detected in cells exposed to WT -Cu 2+ and H50Q -Cu 2+ , likely because of the development of reactive astrocytes, as GFAP staining revealed a phenotype compatible with reactive astrocytes (37) (Fig. 4F).…”

Section: Resultsmentioning

confidence: 99%

Environmental and genetic factors support the dissociation between α-synuclein aggregation and toxicity

Villar‐Piqué

Fonseca

Sant’Anna

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Synucleinopathies are a group of progressive disorders characterized by the abnormal aggregation and accumulation of α-synuclein (aSyn), an abundant neuronal protein that can adopt different conformations and biological properties. Recently, aSyn pathology was shown to spread between neurons in a prion-like manner. Proteins like aSyn that exhibit self-propagating capacity appear to be able to adopt different stable conformational states, known as protein strains, which can be modulated both by environmental and by protein-intrinsic factors. Here, we analyzed these factors and found that the unique combination of the neurodegeneration-related metal copper and the pathological H50Q aSyn mutation induces a significant alteration in the aggregation properties of aSyn. We compared the aggregation of WT and H50Q aSyn with and without copper, and assessed the effects of the resultant protein species when applied to primary neuronal cultures. The presence of copper induces the formation of structurally different and less-damaging aSyn aggregates. Interestingly, these aggregates exhibit a stronger capacity to induce aSyn inclusion formation in recipient cells, which demonstrates that the structural features of aSyn species determine their effect in neuronal cells and supports a lack of correlation between toxicity and inclusion formation. In total, our study provides strong support in favor of the hypothesis that protein aggregation is not a primary cause of cytotoxicity.α-synuclein | copper | H50Q mutation | inclusions | protein aggregation

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Section: Resultsmentioning

confidence: 99%

Environmental and genetic factors support the dissociation between α-synuclein aggregation and toxicity

Villar‐Piqué

Fonseca

Sant’Anna

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…The energy requirement of the brain varies considerably between different cell types, as well as between the control and activated states. Glucose metabolism in the brain is partly controlled by astrocytes through their proximity to blood vessels and neurons, thereby controlling blood flow and regulating the blood brain barrier (43). Therefore, astrocytes are optimal for glucose uptake from the blood.…”

Section: Wnt Signaling Stimulates Glucose Utilization In Neuronsmentioning

confidence: 99%

Activation of Wnt Signaling in Cortical Neurons Enhances Glucose Utilization through Glycolysis

Cisternas

Salazar

Silva-Álvarez

et al. 2016

Journal of Biological Chemistry

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Edited by Jeffrey E. PessinThe Wnt signaling pathway is critical for a number of functions in the central nervous system, including regulation of the synaptic cleft structure and neuroprotection against injury. Deregulation of Wnt signaling has been associated with several brain pathologies, including Alzheimer's disease. In recent years, it has been suggested that the Wnt pathway might act as a central integrator of metabolic signals from peripheral organs to the brain, which would represent a new role for Wnt signaling in cell metabolism. Energy metabolism is critical for normal neuronal function, which mainly depends on glucose utilization. Brain energy metabolism is important in almost all neurological disorders, to which a decrease in the capacity of the brain to utilize glucose has been linked. However, little is known about the relationship between Wnt signaling and neuronal glucose metabolism in the cellular context. In the present study, we found that acute treatment with the Wnt3a ligand induced a large increase in glucose uptake, without changes in the expression or localization of glucose transporter type 3. In addition, we observed that Wnt3a treatment increased the activation of the metabolic sensor Akt. Moreover, we observed an increase in the activity of hexokinase and in the glycolytic rate, and both processes were dependent on activation of the Akt pathway. Furthermore, we did not observe changes in the activity of glucose-6-phosphate dehydrogenase or in the pentose phosphate pathway. The effect of Wnt3a was independent of both the transcription of Wnt target genes and synaptic effects of Wnt3a. Together, our results suggest that Wnt signaling stimulates glucose utilization in cortical neurons through glycolysis to satisfy the high energy demand of these cells.

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“…They modulate the myelinating capacity of the oligodendrocytes 4 , the synaptic cross-talk amongst neurons 5 , the homeostasis of the CNS extracellular medium 6 , the initiation of the inflammatory and immune responses 7 and the building up of barriers between normal and damaged tissues 8 . Astrocytes can behave like phagocytic cells 9 , they sense the partial pressure of O 2 within the CNS 10 and they can transform into neurons when the brain is in need of rebuilding damaged functional neural networks contributing to nervous tissue repair 11 .…”

Section: Astrocytes In Physiologymentioning

confidence: 99%

Are astrocytes executive cells within the central nervous system?

Sica

Caccuri

Quarracino

et al. 2016

Arq. Neuro-Psiquiatr.

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Experimental evidence suggests that astrocytes play a crucial role in the physiology of the central nervous system (CNS) by modulating synaptic activity and plasticity. Based on what is currently known we postulate that astrocytes are fundamental, along with neurons, for the information processing that takes place within the CNS. On the other hand, experimental findings and human observations signal that some of the primary degenerative diseases of the CNS, like frontotemporal dementia, Parkinson’s disease, Alzheimer’s dementia, Huntington’s dementia, primary cerebellar ataxias and amyotrophic lateral sclerosis, all of which affect the human species exclusively, may be due to astroglial dysfunction. This hypothesis is supported by observations that demonstrated that the killing of neurons by non-neural cells plays a major role in the pathogenesis of those diseases, at both their onset and their progression. Furthermore, recent findings suggest that astrocytes might be involved in the pathogenesis of some psychiatric disorders as well.

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Astrocyte Reactivity and Reactive Astrogliosis: Costs and Benefits

Cited by 739 publications

References 281 publications

Environmental and genetic factors support the dissociation between α-synuclein aggregation and toxicity

Environmental and genetic factors support the dissociation between α-synuclein aggregation and toxicity

Activation of Wnt Signaling in Cortical Neurons Enhances Glucose Utilization through Glycolysis

Are astrocytes executive cells within the central nervous system?

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