Abstract
Astrocytes are major glial cells that play critical roles in brain homeostasis. Abnormalities in astrocytic functions can lead to brain disorders. Astrocytes also respond to injury and disease through gliosis and immune activation, which can be both protective and detrimental. Thus, it is essential to elucidate the function of astrocytes in order to understand the physiology of the brain to develop therapeutic strategies against brain diseases. Cyclic adenosine monophosphate (cAMP) is a major second messenger that triggers various downstream cellular machinery in a wide variety of cells. The functions of astrocytes have also been suggested as being regulated by cAMP. Here, we summarize the possible roles of cAMP signaling in regulating the functions of astrocytes. Specifically, we introduce the ways in which cAMP pathways are involved in astrocyte functions, including (1) energy supply, (2) maintenance of the extracellular environment, (3) immune response, and (4) a potential role as a provider of trophic factors, and we discuss how these cAMP-regulated processes can affect brain functions in health and disease.
Highlights
Astrocytes are a major class of glial cells that play a critical role in maintaining the homeostasis of the central nervous system (CNS)
The Cyclic adenosine monophosphate (cAMP) analogue Dibutyryl-cAMP and the adenylyl cyclase (AC) activator forskolin have been shown to trigger glycogenolysis in cultured astrocytes, and inhibitors of protein kinase A (PKA) and soluble AC (sAC) have been shown to completely block astrocytic glycogenolysis induced by isoproterenol or extracellular K+ increases [39,57]. These findings suggest that cAMP can act as the dominant triggering signal for glycogenolysis
Administration of selective β1-adrenergic antagonists before or after ischemic stroke has been shown to attenuate edema development in rats, while selective β2 antagonists have no effect [125]. This phenomenon may be caused by cAMP regulation of NKCC1, as β1-receptor activation by isoproterenol activates glycogenesis, the Na+/K+ ATPase, and NKCC1 to accelerate regulatory volume increase of astrocytes induced by hypertonic stimulation [126]
Summary
Astrocytes are a major class of glial cells that play a critical role in maintaining the homeostasis of the central nervous system (CNS). Astrocytes are in an ideal position to store and supply energy, maintain the extracellular environment after neuronal activity, supply trophic factors, and engage the immune response by interacting with microglia and peripheral immune cells [1]. These functions are important for maintaining proper neuronal activity, preventing oxidative stress, and enabling basic brain functions such as learning and memory [2,3,4,5]. We will introduce the role of astrocytic cAMP in (1) energy supply, (2) maintenance of the extracellular environment, (3) immune response, and (4) a potential role as a provider of trophic factors, and we will discuss how these cAMP-regulated processes can affect the healthy and diseased CNS
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