[HTML][HTML] Normal and abnormal functions of adenosine receptors in the central nervous system revealed by genetic knockout studies
CJ Wei, W Li, JF Chen - Biochimica et biophysica acta (BBA) …, 2011 - Elsevier
CJ Wei, W Li, JF Chen
Biochimica et biophysica acta (BBA)-biomembranes, 2011•ElsevierEndogenous adenosine is a widely distributed upstream regulator of a broad spectrum of
neurotransmitters, receptors, and signaling pathways that converge to contribute to the
expression of an array of important brain functions. Over the past decade, the generation
and characterization of genetic knockout models for all four G-protein coupled adenosine
receptors, the A1 and A2A receptors in particular, has confirmed and extended the
neuromodulatory and integrated role of adenosine receptors in the control of a broad …
neurotransmitters, receptors, and signaling pathways that converge to contribute to the
expression of an array of important brain functions. Over the past decade, the generation
and characterization of genetic knockout models for all four G-protein coupled adenosine
receptors, the A1 and A2A receptors in particular, has confirmed and extended the
neuromodulatory and integrated role of adenosine receptors in the control of a broad …
Endogenous adenosine is a widely distributed upstream regulator of a broad spectrum of neurotransmitters, receptors, and signaling pathways that converge to contribute to the expression of an array of important brain functions. Over the past decade, the generation and characterization of genetic knockout models for all four G-protein coupled adenosine receptors, the A1 and A2A receptors in particular, has confirmed and extended the neuromodulatory and integrated role of adenosine receptors in the control of a broad spectrum of normal and abnormal brain functions. After a brief introduction of the available adenosine receptor knockout models, this review focuses on findings from the genetic knockout approach, placing particular emphasis on the most recent findings. This review is organized into two sections to separately address (i) the role of adenosine receptors in normal brain processes including neuroplasticity, sleep–wake cycle, motor function, cognition, and emotion-related behaviors; and (ii) their role in the response to various pathologic insults to brain such as ischemic stroke, neurodegeneration, or brain dysfunction/disorders. We largely limit our overview to the prominent adenosine receptor subtypes in brain–the A1 and A2A receptors–for which numerous genetic knockout studies on brain function are available. A1 and A2A receptor knockouts have provided significant new insights into adenosine's control of complex physiologic (e.g., cognition) and pathologic (e.g., neuroinflammation) phenomena. These findings extend and strengthen the support for A1 and A2A receptors in brain as therapeutic targets in several neurologic and psychiatric diseases. However, they also emphasize the importance of considering the disease context-dependent effect when developing adenosine receptor-based therapeutic strategies. This article is part of a Special Issue entitled: Adenosine Receptors.
Elsevier
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