title: Phosphodiesterases in the central nervous system: implications in mood and cognitive disorders.
abstract: Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes that are involved in the regulation of the intracellular second messengers cyclic AMP (cAMP) and cyclic GMP (cGMP) by controlling their rates of hydrolysis. There are 11 different PDE families and each family typically has multiple isoforms and splice variants. The PDEs differ in their structures, distribution, modes of regulation, and sensitivity to inhibitors. Since PDEs have been shown to play distinct roles in processes of emotion and related learning and memory processes, selective PDE inhibitors, by preventing the breakdown of cAMP and/or cGMP, modulate mood and related cognitive activity. This review discusses the current state and future development in the burgeoning field of PDEs in the central nervous system. It is becoming increasingly clear that PDE inhibitors have therapeutic potential for the treatment of neuropsychiatric disorders involving disturbances of mood, emotion, and cognition.
authors.affiliation: Departments of Behavioral Medicine & Psychiatry, Neurobiology & Anatomy, and Physiology & Pharmacology and the WVU Center for Neuroscience, West Virginia University Health Sciences Center, WVU HSC/School of Medicine, Morgantown, 9104, WV 26506, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Han-Ting
authors.initials: HT
authors.lastname: Zhang
authors.forename: James M
authors.initials: JM
authors.lastname: O'Donnell
mesh_terms: D001921:Brain / Q000201:enzymology; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D019964:Mood Disorders / Q000188:drug therapy / Q000209:etiology*; D009473:Neuronal Plasticity; D009569:Nitric Oxide / Q000502:physiology; D009712:Nucleotides, Cyclic / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D010727:Phosphoric Diester Hydrolases / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D009712:Nucleotides, Cyclic; D010726:Phosphodiesterase Inhibitors; D009569:Nitric Oxide; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D010727:Phosphoric Diester Hydrolases