Principles of Astrogliopathology

Abstract

The role of astrocytes in the nervous system pathology was early on embraced by neuroscientists at end of the nineteenth and the beginning of the twentieth century, only to be pushed aside by neurone-centric dogmas during most of the twentieth century. However, the last decade of the twentieth century and the twenty-first century have brought the astroglial "renaissance", which has put astroglial cells as key players in pathophysiology of most if not all disorders of the nervous system and has regarded astroglia as a fertile ground for therapeutic intervention.Astrocytic contribution to neuropathology can be primary, whereby cell-autonomous changes, such as mutations in gene encoding for glial fibrillary acidic protein, can drive the pathologic progression, in this example, Alexander disease. They can also be secondary, when astrocytes respond to a variety of insults to the nervous tissue. Regardless of their origin, being cell-autonomous or not, changes in astroglia that occur in pathology, that is, astrogliopathology, can be contemporary and arbitrary classified into four forms: (i) reactive astrogliosis, (ii) astrocytic atrophy with loss of function, (iii) pathological remodelling of astrocytes and (iv) astrodegeneration morphologically manifested as clasmatodendrosis. Inevitably, as with any other classification, this classification of astrogliopathology awaits its revision that shall be rooted in new discoveries and concepts.

Keywords: Astrocyte; Astrocytic atrophy; Neuropathology; Pathological remodelling; Reactive astrogliosis.

Fig. 1

Classification of astrocytic pathological changes. AD Alzheimer’s disease, ALS amyotrophic lateral sclerosis, FTD fronto-temporal dementia, HD Huntington’s disease

Fig. 2

Classification of reactive astrogliosis; see text for explanation. (Modified from Verkhratsky and Butt (2013) and Sofroniew (2009))

Fig. 3

Instigators of reactive astrogliosis. Numerous agents, including damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPS, pathogens), the former originating from various cells in the nervous tissue or from blood. All these agents can activate various astrocytic receptors which launch astrogliotic programmes. Abbreviations: TNF-α tumour necrosis factor α, INF-γ interferon γ, TGF-β transforming growth factor β, FGF fibroblast growth factor, IFG insulin growth factor, NO nitric oxide, ROS reactive oxygen species, LPS lipopolysaccharide

Fig. 4

Age-dependent remodelling of astroglial profiles in different brain areas. Confocal images showing glial fibrillary acidic protein (GFAP) (A to F), s100β (G to L) and glutamine synthetase (GS) (M to R) immunolabelled astrocytes in the dentate gyrus and CA1 hippocampal areas as well as in the entorhinal cortex of mice at 3 and 24 months. (Reproduced, with permission from Verkhratsky et al. (2020a))

Fig. 5

Reconstructions of hippocampal protoplasmic astrocytes from young, adult and old mice. (Reproduced, with permission from Verkhratsky et al. (2020a))