Frontiers in Cellular Neuroscience (Feb 2015)
Metabolic dysfunction in the brain: implications of astrocyte activation
Abstract
Astrocytes are the most abundant cells in the central nervous system (CNS). They participate in different processes such as maintaining the blood–brain barrier and ion homeostasis, uptake and turnover of neurotransmitters, and formation of synapses. In addition, astrocytes also respond to brain insults to prevent the damage. For instance, astrocyte activation plays a central role in the cellular response to brain insults like trauma, infections, stroke, tumorigenesis, and neurodegeneration. However, chronic astrocyte activation can also interfere with normal brain function. Neurodegenerative diseases like Alzheimer’s, Parkinson and amyotrophic lateral sclerosis are characterized by an inflammatory response that is considered the main cause of damage in these CNS disorders. This response is mediated by activated glial cells, which overexpress cytokines like TNF-a, IL-1β, IL-6, and other different pro-inflammatory factors. These pro-inflammatory signalling cascades can cause neurotoxicity and cell-death by reducing the astrocyte capacity of releasing neurotrophic factors, therefore decreasing their repair capability. Astrocyte activation is a dynamic process and its regulation is critical for maintaining an optimal neurological function that avoids the deleterious effects in neuronal survival. However, cellular and functional changes during astrocyte activation can be regulated in a context-specific manner by inter- and intracellular signalling molecules, for example increases in ammonium, glutamate, reactive oxygen species, and nitric oxide favoured astrocyte activation. In this review, we will discuss the state of the art of the metabolic changes that can lead to astrocyte activation and the possible therapeutic approaches to regulate these metabolic changes in astrocytes and their impact in neurons.
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