Reactive Astrocytes in Neurodegenerative Diseases

Li, Kunyu; Li, Jiatong; Zheng, Jialin; Qin, Song

doi:10.14336/ad.2018.0720

Cited by 293 publications

(259 citation statements)

References 117 publications

Supporting

Mentioning

248

Contrasting

Unclassified

Order By: Relevance

“…Numerous studies are providing increasing evidence that neuronal degeneration in a number of neurodegenerative diseases is not only driven by cell-autonomous mechanisms of neuronal death, but is also promoted by non-cell autonomous processes underlying communication between neuronal and glial cells, including astrocytes [Li et al, 2019;Liddelow and Barres, 2017;Siracusa et al, 2019;Yamanaka and Komine, 2018].…”

Section: Discussionmentioning

confidence: 99%

“…Reactive astrocytes mediate a variety of mechanisms, including release of cytokines and chemokines that can participate in complex neuroinflammatory processes, intercellular communication with microglia involved in immune responses, and modulation of immune cell activation at damaged sites. Reactive astrocytes are thought to contribute to either neuroprotective or neuroinflammatory responses depending on the local microenvironment, although evidence exists that astrogliosis is often a complex process characterized by a combination of both inflammatory and protective effects depending on the stage of the damage or injury process [Li et al, 2019;Liddelow and Barres, 2017;Yamanaka and Komine, 2018].…”

Section: Introductionmentioning

confidence: 99%

“…Astrocyte reactivation is a common event in virtually all neurological diseases [Li et al, 2019;Liddelow and Barres, 2017;Siracusa et al, 2019;Yamanaka and Komine, 2018]. For instance, hallmarks of astrocyte activation feature prominently in post-mortem tissues from amyotrophic lateral sclerosis (ALS) patients, as well as in the spinal cord and cranial motor nuclei in ALS transgenic mouse models [Anneser et al, 2004;Baron et al, 2005;Evans et al, 2014;Ferraiuolo et al, 2007;Poloni et al, 2000;Schiffer et al, 1996].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Characterization of human iPSC-derived astrocytes with potential for disease modeling and drug discovery

Soubannier

Maussion

Chaineau

et al. 2019

Preprint

View full text Add to dashboard Cite

ABSTRACTAstrocytes play a number of key functions in health and disease. Reactivation of astrocytes occurs in most, if not all, neurological diseases. Most current information on the mechanisms underlying astrogliosis derives from studies using rodent experimental systems, mainly because the ability to study human astrocytes under healthy and pathological conditions has been hampered by the difficulty in obtaining primary human astrocytes. Here we describe robust and reliable derivation of astrocytes from human induced pluripotent stem cells (iPSCs). Phenotypically characterized human iPSC-derived astrocytes exhibit typical traits of physiological astrocytes, including spontaneous and induced calcium transients. Moreover, human iPSC-derived astrocytes respond to stimulation with a pro-inflammatory combination of tumor necrosis factor alpha, interleukin 1-alpha, and complement component C1q by undergoing changes in gene expression patterns suggesting acquisition of a reactive astrocyte phenotype. Together, these findings provide evidence suggesting that human iPSC-derived astrocytes are a suitable experimental model system to study astrocyte function and reactivation in healthy and pathological conditions of the human nervous system.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of human iPSC-derived astrocytes with potential for disease modeling and drug discovery

Soubannier

Maussion

Chaineau

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…If so, brains of Arl seizure mice would maintain a high level of GFAP intensity and hypertrophied astrocytes with additional long processes. We chose to examine these characteristics, because GFAP is a commonly accepted astrocyte marker that increases expression under reactive conditions, and morphological changes in these cells are characteristic in the development of reactivity [47][48][49][50]. Figure 4e shows that Arl mice with a known history of seizures were found to display heightened intensity of GFAP and additional processes of GFAP positive astrocytes when compared to controls.…”

Section: Arl Mice Exhibit a High Incidence Of Spontaneous Seizurementioning

confidence: 99%

Diverged morphology changes of astrocytic and neuronal primary cilia under reactive insults

et al. 2020

View full text Add to dashboard Cite

Primary cilia are centriole-derived sensory organelles that are present in most mammalian cells, including astrocytes and neurons. Evidence is emerging that astrocyte and neuronal primary cilia demonstrate a dichotomy in the mature mouse brain. However, it is unknown how astrocytic and neuronal primary cilia change their morphology and ciliary proteins when exposed to reactive insults including epilepsy and traumatic brain injury. We used a double transgenic mouse strain (Arl13b-mCherry; Centrin2-GFP), in which we found spontaneous seizures, and a cortical injury model to examine the morphological changes of astrocytic and neuronal primary cilia under reactive conditions. Transgenic overexpression of Arl13b drastically increases the length of astrocytic and neuronal primary cilia in the hippocampus, as well as the cilia lengths of cultured astrocytes and neurons. Spontaneous seizures shorten Arl13b-positive astrocytic cilia and AC3-positive neuronal cilia in the hippocampus. In a cortical injury model, Arl13b is not detectable in primary cilia, but Arl13b protein relocates to the cell body and has robust expression in the proximity of injured tissues. In contrast, the number of AC3-positive cilia near injured tissues remains unchanged, but their lengths become shorter. These results on astrocytic cilia implicate Arl13b in regulating astrocyte proliferation and tissue regeneration, while the shortening of AC3-positive cilia suggests adaptive changes of neuronal primary cilia under excitotoxicity.

show abstract

“…TRPA1 receptors on astrocytes were also suggested to play a role in long-term potentiation in the mouse hippocampus [9]. Since reactive astrocytes can contribute to the progression of neuroinflammation in neurodegenerative diseases [13,14], several workgroups, including ours, had started to investigate the role of TRPA1 in animal models of neurodegenerative diseases. Our previous study aimed at examining the role of TRPA1 in the cuprizone-induced demyelination model in mice.…”

mentioning

confidence: 99%

Investigation of Cuprizone-Induced Demyelination in mGFAP-Driven Conditional Transient Receptor Potential Ankyrin 1 (TRPA1) Receptor Knockout Mice

Kriszta

Nemes

Szepes

et al. 2019

Cells

View full text Add to dashboard Cite

Transient receptor potential ankyrin 1 (TRPA1) receptors are non-selective cation channels responsive to a variety of exogenous irritants and endogenous stimuli including products of oxidative stress. It is mainly expressed by primary sensory neurons; however, expression of TRPA1 by astrocytes and oligodendrocytes has recently been detected in the mouse brain. Genetic deletion of TRPA1 was shown to attenuate cuprizone-induced oligodendrocyte apoptosis and myelin loss in mice.In the present study we aimed at investigating mGFAP-Cre conditional TRPA1 knockout mice in the cuprizone model. These animals were generated by crossbreeding GFAP-Cre +/− and floxed TRPA1 (TRPA1 Fl/Fl ) mice. Cuprizone was administered for 6 weeks and demyelination was followed by magnetic resonance imaging (MRI). At the end of the treatment, demyelination and glial activation was also investigated by histological methods. The results of the MRI showed that demyelination was milder at weeks 3 and 4 in both homozygous (GFAP-Cre +/− TRPA1 Fl/Fl ) and heterozygous (GFAP-Cre +/− TRPA1 Fl/− ) conditional knockout animals compared to Cre −/− control mice. However, by week 6 of the treatment the difference was not detectable by either MRI or histological methods. In conclusion, TRPA1 receptors on astrocytes may transiently contribute to the demyelination induced by cuprizone, however, expression and function of TRPA1 receptors by other cells in the brain (oligodendrocytes, microglia, neurons) warrant further investigation.Cells 2020, 9, 81 2 of 13 and oxidized lipid molecules [1][2][3]. Apart from being a nocisensor for exogenous irritant compounds, it has been suggested to work as a sensor for oxidative stress [4]. Originally described to be localized on a subgroup of nociceptive primary afferent neurons [5,6], it was later revealed that TRPA1 is also expressed at lower levels by various non-neuronal cells including keratinocytes, endothelial cells and cells of the gastrointestinal mucosa [1-3,7]. More importantly, several studies have supported the presence of TRPA1 receptors in the brain on astrocytes [8][9][10], as well as oligodendrocytes [11]. A recent cell-specific transcriptome analysis of the mouse cortex revealed low level expression of TRPA1 on neurons, astrocytes, oligodendrocytes and microglia, as well [12].In astrocytes, TRPA1 receptors were implicated in both physiological and pathophysiological processes. Astrocyte TRPA1 receptors were shown to regulate resting Ca 2+ levels and modulate GABA-ergic inhibitory transmission by reducing GABA transport [8]. TRPA1 receptors on astrocytes were also suggested to play a role in long-term potentiation in the mouse hippocampus [9]. Since reactive astrocytes can contribute to the progression of neuroinflammation in neurodegenerative diseases [13,14], several workgroups, including ours, had started to investigate the role of TRPA1 in animal models of neurodegenerative diseases. Our previous study aimed at examining the role of TRPA1 in the cuprizone-induced demyelination model in mice. Cuprizone...

show abstract

Reactive Astrocytes in Neurodegenerative Diseases

Cited by 293 publications

References 117 publications

Characterization of human iPSC-derived astrocytes with potential for disease modeling and drug discovery

Characterization of human iPSC-derived astrocytes with potential for disease modeling and drug discovery

Diverged morphology changes of astrocytic and neuronal primary cilia under reactive insults

Investigation of Cuprizone-Induced Demyelination in mGFAP-Driven Conditional Transient Receptor Potential Ankyrin 1 (TRPA1) Receptor Knockout Mice

Contact Info

Product

Resources

About