ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Phenotypic conversions of "protoplasmic" to "reactive" astrocytes in Alexander disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 81 citations in OpenAlex.
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Article
- Microglia sense astrocyte dysfunction and prevent disease progression in an Alexander disease model.Brain : a journal of neurology · 2024Article
- Article
- Large-scale gene expression changes in APP/PSEN1 and GFAP mutation models exhibit high congruence with Alzheimer's disease.PloS one · 2024Article
- Article
- Article
- High-resolution transcriptomics informs glial pathology in human temporal lobe epilepsy.Acta neuropathologica communications · 2022Article
- Synaptic hyperexcitability of cytomegalic pyramidal neurons contributes to epileptogenesis in tuberous sclerosis complex.Cell reports · 2022Article
- Heterogeneity of white matter astrocytes in the human brain.Acta neuropathologica · 2022Review
- Alexander disease: models, mechanisms, and medicine.Current opinion in neurobiology · 2022Review
- Case report: Alexander's disease with "head drop" as the main symptom and literature review.Frontiers in neurology · 2022Article
- Effects of advanced age upon astrocyte-specific responses to acute traumatic brain injury in mice.Journal of neuroinflammation · 2020Article
- Control of Astrocyte Quiescence and Activation in a Synthetic Brain Hydrogel.Advanced healthcare materials · 2020Article
- Astrocyte-Oligodendrocyte-Microglia Crosstalk in Astrocytopathies.Frontiers in cellular neuroscience · 2020Review
- Relative stabilities of wild-type and mutant glial fibrillary acidic protein in patients with Alexander disease.The Journal of biological chemistry · 2019Article
- Neuron-glia interactions in the pathophysiology of epilepsy.Nature reviews. Neuroscience · 2019Review
- Discrimination of Prion Strain Targeting in the Central Nervous System via Reactive Astrocyte Heterogeneity in CD44 Expression.Frontiers in cellular neuroscience · 2019Article
- Elevated MeCP2 in Mice Causes Neurodegeneration Involving Tau Dysregulation and Excitotoxicity: Implications for the Understanding and Treatment of MeCP2 Triplication Syndrome.Molecular neurobiology · 2018Article
- The evolving role of neuro-immune interaction in brain repair after cerebral ischemic stroke.CNS neuroscience & therapeutics · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Alexander Disease (AxD) is a primary disorder of astrocytes, caused by heterozygous mutations in GFAP, which encodes the major astrocyte intermediate filament protein, glial fibrillary acidic protein (GFAP). Astrocytes in AxD display hypertrophy, massive increases in GFAP, and the accumulation of Rosenthal fibers, cytoplasmic protein inclusions containing GFAP, and small heat shock proteins. To study the effects of GFAP mutations on astrocyte morphology and physiology, we have examined hippocampal astrocytes in three mouse models of AxD, a transgenic line (GFAP(Tg)) in which the normal human GFAP is expressed in several copies, a knock-in line (Gfap(+/R236H)) in which one of the Gfap genes bears an R236H mutation, and a mouse derived from the mating of these two lines (GFAP(Tg); Gfap(+/R236H)). We report changes in astrocyte phenotype in all lines, with the most severe in the GFAP(Tg);Gfap(+/R236H), resulting in the conversion of protoplasmic astrocytes to cells that have lost their bushy-like morphology because of a reduction of distal fine processes, and become multinucleated and hypertrophic. Astrocytes activate the mTOR cascade, acquire CD44, and lose GLT-1. The altered astrocytes display a microheterogeneity in phenotypes, even neighboring cells. Astrocytes also show diminished glutamate transporter current, are significantly depolarized, and not coupled to adjacent astrocytes. Thus, the accumulation of GFAP in the AxD mouse astrocytes initiates a conversion of normal, protoplasmic astrocytes to astrocytes that display severely "reactive" characteristics, many of which may be detrimental to neighboring neurons and oligodendrocytes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.