The Role of Astrocytes in the Central Nervous System Focused on BK Channel and Heme Oxygenase Metabolites: A Review

Abstract

Astrocytes outnumber neurons in the human brain, and they play a key role in numerous functions within the central nervous system (CNS), including glutamate, ion (i.e., Ca2+, K+) and water homeostasis, defense against oxidative/nitrosative stress, energy storage, mitochondria biogenesis, scar formation, tissue repair via angiogenesis and neurogenesis, and synapse modulation. After CNS injury, astrocytes communicate with surrounding neuronal and vascular systems, leading to the clearance of disease-specific protein aggregates, such as β-amyloid, and α-synuclein. The astrocytic big conductance K+ (BK) channel plays a role in these processes. Recently, potential therapeutic agents that target astrocytes have been tested for their potential to repair the brain. In this review, we discuss the role of the BK channel and antioxidant agents such as heme oxygenase metabolites following CNS injury. A better understanding of the cellular and molecular mechanisms of astrocytes’ functions in the healthy and diseased brains will greatly contribute to the development of therapeutic approaches following CNS injury, such as Alzheimer’s disease, Parkinson’s disease, and stroke.

The Role of a Neurovascular Signaling Pathway Involving Hypoxia-Inducible Factor and Notch in the Function of the Central Nervous System

“…AD and PD pathology is characterized by progressive Aβ, α-synuclein, and neurofibrillary tangle accumulation, as well as cytoskeletal and synapse disruption; additionally, inflammation and deficits in the expression of neurotrophic factors, transcription factors, and antioxidant enzymes have been implicated in the pathophysiology of AD and PD (Lee and Choi, 2018; Kim et al ., 2019). Altogether, these multi-faceted events underscore the complexity and therapeutic challenges associated with CNS diseases.…”

Electrospun Fiber Scaffolds for Engineering Glial Cell Behavior to Promote Neural Regeneration

“…The main glial cell types in the CNS are astrocytes, oligodendrocytes, and microglia (depicted in Figure 2 B). Astrocytes are the most prevalent glia in the CNS and serve multiple dynamic biological functions, including the modulation of synaptic connections between neurons, continuous sequestering of toxic species, and providing a physical barrier with other cells, known as the blood–brain barrier, between the CNS and all neighboring vasculature [ 42 , 43 , 44 ]. While both astrocytes and oligodendrocytes display projections from their cell bodies, those from oligodendrocytes specifically construct the myelin sheath around nearby neurons, a concentric wrapping that improves neuron repolarization and conduction speeds.…”

Glial restricted precursor cells in central nervous system disorders: Current applications and future perspectives

“…Astrocytes are able to communicate with neuronal and vascular systems after injury and this allows the use of these cells as possible therapeutic agents due to their regenerative potential (Y. Kim, Park, & Choi, 2019). Given the morphological and functional heterogeneity of astrocytes, their pathological dysfunction is associated with neurodevelopment diseases, such as Rett syndrome and fragile X syndrome, but also to aging-associated diseases such as Alzheimer's (Habib et al, 2020;Miller, Zhang, Glatzer, & Rothstein, 2017).…”