ArticleNeuroscience2016
PDE11A regulates social behaviors and is a key mechanism by which social experience sculpts the brain.
Article in Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Under or Absent Reporting of Light Stimuli in Testing of Anxiety-Like Behaviors in Rodents: The Need for Standardization.Frontiers in molecular neuroscience · 2022Pooled it
- 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
- 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
- Identification of Neurotransmission and Synaptic Biological Processes Disrupted in Autism Spectrum Disorder Using Interaction Networks and Community Detection Analysis.Biomedicines · 2023Article
- Conserved age-related increases in hippocampal PDE11A4 cause unexpected proteinopathies and cognitive decline of social associative memories.Aging cell · 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
- Genome-wide study of copy number variation implicates multiple novel loci for schizophrenia risk in Han Chinese family trios.iScience · 2021Article
- Gene-based mediation analysis in epigenetic studies.Briefings in bioinformatics · 2021Article
- Relaxin-3 Innervation From the Nucleus Incertus to the Parahippocampal Cortex of the Rat.Frontiers in neuroanatomy · 2021Article
- The Role of PDE11A4 in Social Isolation-Induced Changes in Intracellular Signaling and Neuroinflammation.Frontiers in pharmacology · 2021Article
- Therapeutic Potential of Phosphodiesterase Inhibitors against Neurodegeneration: The Perspective of the Medicinal Chemist.ACS chemical neuroscience · 2020Review
- Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.Nature reviews. Drug discovery · 2019Review
- Loss of Function of Phosphodiesterase 11A4 Shows that Recent and Remote Long-Term Memories Can Be Uncoupled.Current biology : CB · 2019Article
- Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn.Scientific reports · 2018Article
- Identification of new PDE9A isoforms and how their expression and subcellular compartmentalization in the brain change across the life span.Neurobiology of aging · 2018Article
- Cyclic nucleotide signaling changes associated with normal aging and age-related diseases of the brain.Cellular signalling · 2018Review
- PDE11A negatively regulates lithium responsivity.Molecular psychiatry · 2017Article
- A Role for Phosphodiesterase 11A (PDE11A) in the Formation of Social Memories and the Stabilization of Mood.Advances in neurobiology · 2017Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Despite the fact that appropriate social behaviors are vital to thriving in one's environment, little is understood of the molecular mechanisms controlling social behaviors or how social experience sculpts these signaling pathways. Here, we determine if Phosphodiesterase 11A (PDE11A), an enzyme that is enriched in the ventral hippocampal formation (VHIPP) and that breaks down cAMP and cGMP, regulates social behaviors. PDE11 wild-type (WT), heterozygous (HT), and knockout (KO) mice were tested in various social approach assays and gene expression differences were measured by RNA sequencing. The effect of social isolation on PDE11A4 compartmentalization and subsequent social interactions and social memory was also assessed. Deletion of PDE11A triggered age- and sex-dependent deficits in social approach in specific social contexts but not others. Mice appear to detect altered social behaviors of PDE11A KO mice, because C57BL/6J mice prefer to spend time with a sex-matched PDE11A WT vs. its KO littermate; whereas, a PDE11A KO prefers to spend time with a novel PDE11A KO vs. its WT littermate. Not only is PDE11A required for intact social interactions, we found that 1month of social isolation vs. group housing decreased PDE11A4 protein expression specifically within the membrane fraction of VHIPP. This isolation-induced decrease in PDE11A4 expression appears functional because social isolation impairs subsequent social approach behavior and social memory in a PDE11A genotype-dependent manner. Pathway analyses following RNA sequencing suggests PDE11A is a key regulator of the oxytocin pathway and membrane signaling, consistent with its pivotal role in regulating social behavior.
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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.