Astrocytes: Role and Functions in Brain Pathologies

Abstract

Astrocytes are a population of cells with distinctive morphological and functional characteristics that differ within specific areas of the brain. Postnatally, astrocyte progenitors migrate to reach their brain area and related properties. They have a regulatory role of brain functions that are implicated in neurogenesis and synaptogenesis, controlling blood–brain barrier permeability and maintaining extracellular homeostasis. Mature astrocytes also express some genes enriched in cell progenitors, suggesting they can retain proliferative potential. Considering heterogeneity of cell population, it is not surprising that their disorders are related to a wide range of different neuro-pathologies. Brain diseases are characterized by the active inflammatory state of the astrocytes, which is usually described as up-regulation of glial fibrillary acidic protein (GFAP). In particular, the loss of astrocytes function as a result of cellular senescence could have implications for the neurodegenerative disorders, such as Alzheimer disease and Huntington disease, and for the aging brain. Astrocytes can also drive the induction and the progression of the inflammatory state due to their Ca2+ signals and that it is strongly related to the disease severity/state. Moreover, they contribute to the altered neuronal activity in several frontal cortex pathologies such as ischemic stroke and epilepsy. There, we describe the current knowledge pertaining to astrocytes’ role in brain pathologies and discuss the possibilities to target them as approach toward pharmacological therapies for neuro-pathologies.

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

“…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].…”

“…Astrocytes play a number of important roles in the healthy nervous system by supporting neuronal activity in several ways, including regulation of synaptic transmission, release of neurotrophic factors, promotion of neuronal metabolic functions, and cross-talk with other glial cells, to name only a few [reviewed by Zhou et al, 2019;Zuchero and Barres, 2015]. Astrocytes are also important players in the injured or diseased nervous system, when they can acquire 'reactive' phenotypes, characterized by morphological and gene expression changes during a process often termed astrogliosis [reviewed by Liddelow and Barres, 2017;Siracusa et al, 2019;Valori et al, 2019]. 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.…”

“…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].…”

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

“…The glial fibrillary acidic protein (GFAP) is a generally accepted marker of astrocytes. Brain diseases are characterized by the active inflammatory state of astrocytes, which is usually manifested as up-regulation of GFAP [28].…”

The interrupted effect of autophagic flux and lysosomal function induced by graphene oxide in p62-dependent apoptosis of F98 cells

“…Exposure to silver NPs or zinc oxide NPs can induce oxidative stress and apoptosis of astrocytes [22,23]. In addition, toxic effects on astrocytes are related to many neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, ischemic stroke and epilepsy [24,25]. Considering the crucial role of astrocytes and the great potential application of GO in the CNS, studying the effect and specific mechanism of GO on astrocytes is urgently required.…”