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作者

Zhang, C. Lueptow, L.M. Zhang, H.-T. O’Donnell, J.M. Xu, Y.

作者单位

Department of Behavioral Medicine and Psychiatry, West Virginia University Health Sciences Center, f Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14214, United States Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Medical Center Drive, Morgantown, WV 26506, United States Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States a Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14214, United States Institute of Pharmacology, Taishan Medical University, Taian, 271016, China

刊名

Advances in Neurobiology

年份

2017

卷号

Vol.17

页码

307-347

ISSN

2190-5215

关键词

Anxiety Depression HPA axis Memory and cognition Pain PDE2 Stress

摘要

Cyclic nucleotide PDEs are a super-family of enzymes responsible for regulating intracellular levels of the second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate . Through their catalysis, PDEs are able to exert tight regulation over these important intracellular signaling cascades. Previously, PDEs have been implicated in learning and memory, as well as in mood disorders, such as anxiety and depression. PDE2 is of special interest due to its high level of expressi...更多

Cyclic nucleotide PDEs are a super-family of enzymes responsible for regulating intracellular levels of the second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate . Through their catalysis, PDEs are able to exert tight regulation over these important intracellular signaling cascades. Previously, PDEs have been implicated in learning and memory, as well as in mood disorders, such as anxiety and depression. PDE2 is of special interest due to its high level of expression in the forebrain, specifically in the isocortex, entorhinal cortex, striatum, hippocampus, amygdala, and medial habenula. Many of these brain regions are considered participants of the limbic system, which is known as the emotional regulatory center of the brain, and is important for modulating emotion and long-term memory. Therefore, PDE2s coincidental expression in these areas suggests an important role for PDE2 in these behaviors, and researchers are continuing to uncover the complex connections. It was shown that PDE2 inhibitors have pro-cognitive effects in tests of memory, including the object recognition test. PDE2 inhibitors are also protective against cognitive deficits in various models of cognitive impairment. Additionally, PDE2 inhibitors are protective against many different forms of stress-induced anxiety-like and depression-like behaviors. Currently, there is a great need for novel therapeutics for the treatment of mood and cognitive disorders, especially anxiety and depression, and other neurodegenerative diseases, such as Alzheimer’s disease, and PDE2 is emerging as a viable target for future drug development for many of these diseases.收起

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