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PDE9A
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High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A (EC 3.1.4.35) ==Publications== {{medline-entry |title=Identification of new [[PDE9A]] isoforms and how their expression and subcellular compartmentalization in the brain change across the life span. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29505961 |abstract=3',5'-Cyclic nucleotide phosphodiesterases (PDEs) degrade 3',5' cyclic adenonosine monophosphate (cAMP) and 3',5' cyclic guanosine monophosphate (cGMP), with [[PDE9A]] having the highest affinity for cGMP. We show [[PDE9A]]6 and 3 novel PDE9 isoforms (PDE9X-100, PDE9X-120, and PDE9X-175) are reliably detected in the brain and lung of mice, whereas [[PDE9A]]2 and other isoforms are found elsewhere. [[PDE9A]] localizes to the membrane in all organs except the bladder, where it is cytosolic. Brain additionally shows PDE9 in the nuclear fraction. [[PDE9A]] mRNA expression/localization dramatically changes across neurodevelopment in a manner that is strikingly consistent between mice and humans (i.e., decreased expression in the hippocampus and cortex and inverted-U in the cerebellum). Study of the 4 PDE9 isoforms in the mouse brain from postnatal day 7 through 24 months similarly identifies dramatic effects of age on expression and subcellular compartmentalization that are isoform specific and brain region specific. Finally, [[PDE9A]] mRNA is elevated in the aged human hippocampus with dementia when there is a history of traumatic brain injury. Thus, brain PDE9 is localized to preferentially regulate nuclear- and membrane-proximal pools of cGMP, and its function likely changes across the life span. |mesh-terms=* 3',5'-Cyclic-AMP Phosphodiesterases * Aging * Animals * Brain * Cell Compartmentation * Cyclic GMP * Gene Expression * Humans * Mice, Inbred C57BL * Mice, Knockout * Protein Isoforms * RNA, Messenger * Subcellular Fractions |keywords=* Aging * Allen institute for Brain Science * Cerebellum * Development * GAPDH * Hippocampus * Phosphodiesterase * Ponceau * Prefrontal cortex * Striatum * cGMP |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871571 }} {{medline-entry |title=Select 3',5'-cyclic nucleotide phosphodiesterases exhibit altered expression in the aged rodent brain. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24184653 |abstract=3',5'-cyclic nucleotide phosphodiesterases (PDEs) are the only known enzymes to compartmentalize cAMP and cGMP, yet little is known about how PDEs are dynamically regulated across the lifespan. We mapped mRNA expression of all 21 PDE isoforms in the adult rat and mouse central nervous system (CNS) using quantitative polymerase chain reaction (qPCR) and in situ hybridization to assess conservation across species. We also compared PDE mRNA and protein in the brains of old (26 months) versus young (5 months) Sprague-Dawley rats, with select experiments replicated in old (9 months) versus young (2 months) BALB/cJ mice. We show that each PDE isoform exhibits a unique expression pattern across the brain that is highly conserved between rats, mice, and humans. [[PDE1B]], [[PDE1C]], [[PDE2A]], [[PDE4A]], [[PDE4D]], [[PDE5A]], [[PDE7A]], [[PDE8A]], [[PDE8B]], [[PDE10A]], and [[PDE11A]] showed an age-related increase or decrease in mRNA expression in at least 1 of the 4 brain regions examined (hippocampus, cortex, striatum, and cerebellum). In contrast, mRNA expression of [[PDE1A]], [[PDE3A]], [[PDE3B]], [[PDE4B]], [[PDE7A]], [[PDE7B]], and [[PDE9A]] did not change with age. Age-related increases in [[PDE11A]]4, [[PDE8A]]3, [[PDE8A]]4/5, and [[PDE1C]]1 protein expression were confirmed in hippocampus of old versus young rodents, as were age-related increases in [[PDE8A]]3 protein expression in the striatum. Age-related changes in PDE expression appear to have functional consequences as, relative to young rats, the hippocampi of old rats demonstrated strikingly decreased phosphorylation of GluR1, CaMKIIα, and CaMKIIβ, decreased expression of the transmembrane AMPA regulatory proteins γ2 (a.k.a. stargazin) and γ8, and increased trimethylation of H3K27. Interestingly, expression of [[PDE11A]]4, [[PDE8A]]4/5, [[PDE8A]]3, and [[PDE1C]]1 correlate with these functional endpoints in young but not old rats, suggesting that aging is not only associated with a change in PDE expression but also a change in PDE compartmentalization. |mesh-terms=* 3',5'-Cyclic-AMP Phosphodiesterases * Aging * Animals * Brain * Cerebellum * Cerebral Cortex * Corpus Striatum * Gene Expression Regulation, Enzymologic * Hippocampus * Male * Mice * Mice, Inbred BALB C * Protein Isoforms * RNA, Messenger * Rats * Rats, Sprague-Dawley |keywords=* Alzheimer's disease * Model * Neuron * PDE11 * PDE8 * Tissue distribution |full-text-url=https://sci-hub.do/10.1016/j.cellsig.2013.10.007 }}
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