Structural and Functional Heterogeneity of Astrocytes in the Brain: Role in Neurodegeneration and Neuroinflammation

Abstract

The review covers the current concepts on structural and functional heterogeneity of brain astrocytes that serve for numerous (patho)physiological processes in the central nervous system. Astrocytes from various subpopulations demonstrate different sensitivity to the action of pathogenic factors, varied behaviors in reactive processes and within the local immune response. Key functions of astrocytes like neurogenesis, neuron-astroglia metabolic coupling, glial control of local blood flow greatly depend on the origin and characteristics of astroglial cells. Changes at the initial stages of neurodegeneration or in neurodevelopmental disorders are associated with significant alterations in astroglial structural and functional properties, thus suggesting new approaches to therapeutic strategies implementing astroglia-expressing molecules and targets for effective

Genetic Constructs for the Control of Astrocytes’ Activity

“…This diversity of molecular markers makes it challenging to identify astrocytes by detecting a single marker such as glial fibrillary acidic protein (GFAP) or s100β protein expression alone. There are several subgroups of astrocytes in rodent and primate central nervous systems, such as: radial astroglia (GLAST+(–)/GFAP(+)(–)/Pax6+/FABP7+/Nestin+/Vimentin+/Pax6+/Cx43+/Cx30 cells) originating from neuroepithelial cells that are involved in embryonic and adult neurogenesis; protoplasmic astrocytes (GFAP++/s100β+/EAAT+/AQP4+/NDRG2+/Cx43/CD38+), which are the principal glial constituents of the neurovascular unit; they stay close to neurons due to direct contacts made by their perisynaptic processes and control neuronal excitability, plasticity, metabolic status, and close to brain microvessel endothelial cells due to their end-feet contacts to adjust local microcirculation to the actual needs of neurons; fibrous astrocytes (GFAP+(–)/CD44+ cells) surrounding myelinated fibers and controlling myelinization; iv) reactive astrocytes with upregulated expression of GFAP (GFAP++/EAAT+/Nestin+/Vimentin+/PDGFR+/Musashi+/CD44+/CD38+/Lcn-2+ cells) that take part in the progression of local inflammation and gliosis [ 11 , 12 , 13 , 14 , 15 ]. …”

“…fibrous astrocytes (GFAP+(–)/CD44+ cells) surrounding myelinated fibers and controlling myelinization; iv) reactive astrocytes with upregulated expression of GFAP (GFAP++/EAAT+/Nestin+/Vimentin+/PDGFR+/Musashi+/CD44+/CD38+/Lcn-2+ cells) that take part in the progression of local inflammation and gliosis [ 11 , 12 , 13 , 14 , 15 ].…”

Novel Approaches Used to Examine and Control Neurogenesis in Parkinson′s Disease

“…The expression of light-sensitive molecules under the control of the astroglial promoter (GFAP) raises the question of what type of cells within the neurogenic niche could be affected by photostimulation. Even though there is a heterogeneity of astroglial cells, the expression of GFAP could be easily detected in the majority of mature resting and reactive astrocytes throughout the brain [180]. Higher expression of GFAP in reactive astrocytes, particularly in neurodegeneration [181], makes it possible to increase the efficacy of photostimulation in the affected brain vs. the healthy brain.…”

Relation between the Severity of the Sensorimotor Cortical Edema with Cell Swelling and the Duration of Common Carotid Artery Occlusion in Rats (Morphometric Study)

“…Функционирование, восстановление и гибель нейронов происходит в едином комплексе с астроцитами и микрососудами [13][14][15][16]. После острой ишемии дальнейшая судьба нейроглиального комплекса окончательно определяется в течение 24-48 ч. В случае неблагоприятного исхода деструкции подвергаются некробиотически измененные нейроны и связанные с ними отростки астроцитов [12].…”

“…Neuronal functioning, recovery and death occur together with astrocytes and microvessels [13][14][15][16]. After acute ischemia, the further fate of neuroglial complex is ultimately determined within 24-48 h. In case of unfavorable outcome, necrobiotic neurons and associated astrocyte processes undergo destruction [12].…”