Translational potential of astrocytes in brain disorders

Abstract

Fundamentally, all brain disorders can be broadly defined as the homeostatic failure of this organ. As the brain is composed of many different cells types, including but not limited to neurons and glia, it is only logical that all the cell types/constituents could play a role in health and disease. Yet, for a long time the sole conceptualization of brain pathology was focused on the well-being of neurons. Here, we challenge this neuron-centric view and present neuroglia as a key element in neuropathology, a process that has a toll on astrocytes, which undergo complex morpho-functional changes that can in turn affect the course of the disorder. Such changes can be grossly identified as reactivity, atrophy with loss of function and pathological remodeling. We outline the pathogenic potential of astrocytes in variety of disorders, ranging from neurotrauma, infection, toxic damage, stroke, epilepsy, neurodevelopmental, neurodegenerative and psychiatric disorders, Alexander disease to neoplastic changes seen in gliomas. We hope that in near future we would witness glial-based translational medicine with generation of deliverables for the containment and cure of disorders. We point out that such as a task will require a holistic and multi-disciplinary approach that will take in consideration the concerted operation of all the cell types in the brain.

Calcineurin proteolysis in astrocytes: Implications for impaired synaptic function

“…Astrocytes may also be an important source for CN dysregulation [10], which is notable given the increasing attention astrocytes have received for their contributions to neurologic dysfunction during aging, injury, and disease [64–67]. Overexpression of ΔCN in astrocytes leads to the production and release of a variety of immune factors ( e.g.…”

Astroglia in Sepsis Associated Encephalopathy

“…Astrocytes are key players in neuropathology; contemporary views regard astroglial changes as an obligatory component of neurological diseases [64][65][66][67][68][69]. Pathological changes in astrocytes are multifaceted and are disease and disease-stage specific.…”

“…Pathological changes in astrocytes are multifaceted and are disease and disease-stage specific. Conceptually, astrogliopathology is sub-classified into (i) reactive astrogliosis and (ii) astrocytopathies represented by astodegeneration with astroglial atrophy and loss of function and astroglial pathological remodelling [65,66,70].…”

Inflammatory Activation of Microglia and Astrocytes in Manganese Neurotoxicity

“…Mn causes metabolic changes in astrocytic glucose metabolism by inhibition of the astrocyte-specific enzyme, glutamine synthetase (GS), thereby contributing to downregulation of glutamate transporters and compromising glutamate uptake (Suarez-Fernandez et al 1999; Verkhratski and Butt 2013; Yin et al 2007; Verkhratsky et al 2016). These oxidative changes are consistent with the combined effects of Mn and inflammatory stimuli on mitochondrial function in astrocytes, which promotes greater production of ROS and deprecations in metabolic support of neurons, in addition to the damaging effects of inflammatory gene expression (Barhoumi et al 2004).…”