ArticleNeurobiology of aging2015
Inhibition of phosphodiesterase 2 reverses impaired cognition and neuronal remodeling caused by chronic stress.
Article in Neurobiology of aging, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Validity of chronic restraint stress for modeling anhedonic-like behavior in rodents: a systematic review and meta-analysis.The Journal of international medical research · 2022Pooled it
- The Potential Anti Stress-like Properties of Escitalopram on Improvement of Spatial Memory in Rats Subjected to Predictable and Unpredictable Chronic Mild Stress.Advanced biomedical research · 2026Article
- Transcriptomic Insights into Late-Life Depression and the Role of Environmental Drinking Water Composition: A Study on 18-Month-Old Mice.International journal of molecular sciences · 2025Article
- Effects of Different Ways of Music Stimulation on Exploring, Playing and Aggressive Behavior.Animals : an open access journal from MDPI · 2025Article
- Effects of Qingyangshen glycosides on neuroplasticity in a mouse model of social defeat.Animal models and experimental medicine · 2025Article
- Chronic ethanol administration exacerbates memory loss by altering N6-methyladenosine-mediated epigenetic signaling.Frontiers in immunology · 2025Article
- Histone 3 Trimethylation Patterns are Associated with Resilience or Stress Susceptibility in a Rat Model of Major Depression Disorder.Molecular neurobiology · 2024Article
- Early growth response 1 (EGR1) is downregulated in peripheral blood from patients with major psychiatric disorders.Trends in psychiatry and psychotherapy · 2024Article
- Characterization of 2 Novel Phosphodiesterase 2 Inhibitors Hcyb1 and PF-05180999 on Depression- and Anxiety-Like Behavior.The international journal of neuropsychopharmacology · 2023Article
- Cognitive and Emotional Symptoms Induced by Chronic Stress Are Regulated by EGR1 in a Subpopulation of Hippocampal Pyramidal Neurons.International journal of molecular sciences · 2023Article
- Baicalein-corrected gut microbiota may underlie the amelioration of memory and cognitive deficits in APP/PS1 mice.Frontiers in pharmacology · 2023Article
- Inhibition of Phosphodiesterase 2 Ameliorates Post-Traumatic Stress-Induced Alcohol Intake Disorder by Regulating cAMP/cGMP Signaling.The international journal of neuropsychopharmacology · 2022Article
- Meridianins Inhibit GSK3β In Vivo and Improve Behavioral Alterations Induced by Chronic Stress.Marine drugs · 2022Article
- MicroRNAs as novel peripheral markers for suicidality in patients with major depressive disorder.Frontiers in psychiatry · 2022Article
- Acute gene expression changes in the mouse hippocampus following a combined Gulf War toxicant exposure.Life sciences · 2021Article
- TheJournal of neurogenetics · 2021Article
- Design, Synthesis, and Evaluation of Dihydropyranopyrazole Derivatives as Novel PDE2 Inhibitors for the Treatment of Alzheimer's Disease.Molecules (Basel, Switzerland) · 2021Article
- DL-3-n-butylphthalide ameliorates diabetes-associated cognitive decline by enhancing PI3K/Akt signaling and suppressing oxidative stress.Acta pharmacologica Sinica · 2021Article
- Article
- Phosphodiesterase-4D Knockdown in the Prefrontal Cortex Alleviates Memory Deficits and Synaptic Failure in Mouse Model of Alzheimer's Disease.Frontiers in aging neuroscience · 2021Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Chronic stress and neuronal vulnerability have recently been recognized as factors contributing to cognitive disorders. One way to modify neuronal vulnerability is through mediation of phosphodiesterase 2 (PDE2), an enzyme that exerts its action on cognitive processes via the control of intracellular second messengers, cGMP and, to a lesser extent, cAMP. This study explored the effects of a PDE2 inhibitor, Bay 60-7550, on stress-induced learning and memory dysfunction in terms of its ramification on behavioral, morphologic, and molecular changes. Bay 60-7550 reversed stress-induced cognitive impairment in the Morris water maze, novel object recognition, and location tasks (object recognition test and/or object location test), effects prevented by treatment with 7-NI, a selective inhibitor of neuronal nitric oxide synthase; MK801, a glutamate receptor (NMDAR) inhibitor; myr-AIP, a CaMKII inhibitor; and KT5823, a protein kinase G inhibitor. Bay 60-7550 also ameliorated stress-induced structural remodeling in the CA1 of the hippocampus, leading to increases in dendritic branching, length, and spine density. However, the neuroplasticity initiated by Bay 60-7550 was not seen in the presence of 7-NI, MK801, myr-AIP, or KT5823. PDE2 inhibition reduced stress-induced extracellular-regulated protein kinase activation and attenuated stress-induced decreases in transcription factors (e.g., Elk-1, TORC1, and CREB phosphorylation) and plasticity-related proteins (e.g., Egr-1 and brain-derived neurotrophic factor). Pretreatment with inhibitors of NMDA, CaMKII, neuronal nitric oxide synthase, and protein kinase G (or protein kinase A) blocked the effects of Bay 60-7550 on cGMP or cAMP signaling. These findings indicate that the effect of PDE2 inhibition on stress-induced memory impairment is potentially mediated via modulation of neuroplasticity-related NMDAR-CaMKII-cGMP/cAMP signaling.
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Registered trials
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