Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies

Abstract

Astrocytes, as the most abundant glial cells in the central nervous system, are tightly integrated into neural networks and participate in numerous aspects of brain physiology and pathology. They are the main homeostatic cells in the central nervous system, and the loss of astrocyte physiological functions and/or gain of pro-inflammatory functions, due to their reactivation or cellular senescence, can have profound impacts on the surrounding microenvironment with pathological outcomes. Although the importance of astrocytes is generally recognized, and both senescence and reactive astrogliosis have been extensively reviewed independently, there are only a few comparative overviews of these complex processes. In this review, we summarize the latest data regarding astrocyte reactivation and senescence, and outline similarities and differences between these phenotypes from morphological, functional, and molecular points of view. A special focus has been given to neurodegenerative diseases, where these phenotypic alternations of astrocytes are significantly implicated. We also summarize current perspectives regarding new advances in model systems based on astrocytes as well as data pointing to these glial cells as potential therapeutic targets.

Effects of High-Fat and High-Fat High-Sugar Diets in the Anxiety, Learning and Memory, and in the Hippocampus Neurogenesis and Neuroinflammation of Aged Rats

“…However, we can also consider that although under astrocytosis, they could start to defeat and shrink. To verify this, we believe that astrocytes may experience a mechanism of cell death, such as apoptosis, pyroptosis, or even senescence, as reported in other studies [ 63 , 64 ]. At the same time, gliogenesis may also occur because stem cells that become neurons can also become astrocytes, especially during aging [ 20 ].…”

The Role of SOX Transcription Factors in Ageing and Age-Related Diseases

“…[55]. Recent findings indicate that senescent astrocytes and the accompanying senescence-associated secretory phenotype are correlated with different neurodegenerative disorders [180]. Accordingly, the elimination or reversal of cell senescence by genetic manipulations or pharmacological approaches may exert beneficial effects on neurodegenerative brains [181][182][183].…”

The relationships between neuroglial and neuronal changes in Alzheimer’s disease, and the related controversies II: gliotherapies and multimodal therapy

“… 47 , 48 Although senescence has been demonstrated in some neurons, the majority of senescent cells in brain are of neuroglial linages. 47 , 48 Senescent astrocytes, 49 - 53 oligodendrocytes 54 and microglial cells 55 have been observed and studied. These cells are characterized by growth arrest (in tissue or in culture after isolation), increased expression of senescence-associated genes p53 and p21WAF1 and increased senescence-associated β-galactosidase (SA-β-Gal) activity, 50 , 56 , 57 as well as a characteristic development of a multicomponent senescence-associated secretory phenotype (SASP).…”

“…These cells are characterized by growth arrest (in tissue or in culture after isolation), increased expression of senescence-associated genes p53 and p21WAF1 and increased senescence-associated β-galactosidase (SA-β-Gal) activity, 50 , 56 , 57 as well as a characteristic development of a multicomponent senescence-associated secretory phenotype (SASP). 49 - 53 , 58 The SASP consists of a myriad of cytokines, chemokines (CXCLs), growth factors, and proteases that initiate neuroinflammation or, in the contrary, growth responses in nearby cells. In young healthy tissues, the SASP is typically transient and tends to contribute to the preservation or restoration of tissue homeostasis.…”