ArticleProceedings of the National Academy of Sciences of the United States of America2010
Phosphodiesterase 11A in brain is enriched in ventral hippocampus and deletion causes psychiatric disease-related phenotypes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 82 citations in OpenAlex.
- Genetic Association of Sexual Behavior, Sildenafil, and Hormonal Contraceptives With Mental Disorders.CNS neuroscience & therapeutics · 2026Article
- The Emerging Role of Phosphodiesterase Inhibitors in Fragile X Syndrome and Autism Spectrum Disorder.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- In the Brain of Phosphodiesterases: Potential Therapeutic Targets for Schizophrenia.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2025Review
- Exploring PDE5A upregulation in bipolar disorder: insights from single-nucleus RNA sequencing of human basal ganglia.Translational psychiatry · 2024Article
- First Demonstration ofJournal of medicinal chemistry · 2024Article
- Article
- The sleep quality- and myopia-linked PDE11A-Y727C variant impacts neural physiology by reducing catalytic activity and altering subcellular compartmentalization of the enzyme.bioRxiv : the preprint server for biology · 2023Article
- First Optimization of Novel, Potent, Selective PDE11A4 Inhibitors for Age-Related Cognitive Decline.Journal of medicinal chemistry · 2023Article
- Biologic that disrupts PDE11A4 homodimerization in hippocampus CA1 reverses age-related cognitive decline of social memories in mice.Neurobiology of aging · 2023Article
- Anatomical and molecular features of the amygdalohippocampal transition area and its role in social and emotional behavior processes.Neuroscience and biobehavioral reviews · 2022Review
- Conserved age-related increases in hippocampal PDE11A4 cause unexpected proteinopathies and cognitive decline of social associative memories.Aging cell · 2022Article
- Functional characteristics and research trends of PDE11A in human diseases (Review).Molecular medicine reports · 2022Article
- A genetic basis for friendship? Homophily for membrane-associated PDE11A-cAMP-CREB signaling in CA1 of hippocampus dictates mutual social preference in male and female mice.Molecular psychiatry · 2021Article
- Review
- Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders.Molecular psychiatry · 2021Review
- Exome sequencing revealed PDE11A as a novel candidate gene for early-onset Alzheimer's disease.Human molecular genetics · 2021Article
- The Role of PDE11A4 in Social Isolation-Induced Changes in Intracellular Signaling and Neuroinflammation.Frontiers in pharmacology · 2021Article
- Sociability development in mice with cell-specific deletion of the NMDA receptor NR1 subunit gene.Genes, brain, and behavior · 2020Article
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Authors and funding
21 authors at 2 institutions in 2 countries.
Funding
Abstract
Phosphodiesterase 11A (PDE11A) is the most recently identified family of phosphodiesterases (PDEs), the only known enzymes to break down cyclic nucleotides. The tissue expression profile of this dual specificity PDE is controversial, and little is understood of its biological function, particularly in the brain. We seek here to determine if PDE11A is expressed in the brain and to understand its function, using PDE11A(-/-) knockout (KO) mice. We show that PDE11A mRNA and protein are largely restricted to hippocampus CA1, subiculum, and the amygdalohippocampal area, with a two- to threefold enrichment in the ventral vs. dorsal hippocampus, equal distribution between cytosolic and membrane fractions, and increasing levels of protein expression from postnatal day 7 through adulthood. Interestingly, PDE11A KO mice show subtle psychiatric-disease-related deficits, including hyperactivity in an open field, increased sensitivity to the glutamate N-methyl-D-aspartate receptor antagonist MK-801, as well as deficits in social behaviors (social odor recognition memory and social avoidance). In addition, PDE11A KO mice show enlarged lateral ventricles and increased activity in CA1 (as per increased Arc mRNA), phenotypes associated with psychiatric disease. The increased sensitivity to MK-801 exhibited by PDE11A KO mice may be explained by the biochemical dysregulation observed around the glutamate alpha-amino-3-hydroxy-5-methyl-4-isozazolepropionic (AMPA) receptor, including decreased levels of phosphorylated-GluR1 at Ser845 and the prototypical transmembrane AMPA-receptor-associated proteins stargazin (gamma2) and gamma8. Together, our data provide convincing evidence that PDE11A expression is restricted in the brain but plays a significant role in regulating brain function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.