ArticleScientific reports2015
Phosphodiesterase-4D Knock-down in the Prefrontal Cortex Alleviates Chronic Unpredictable Stress-Induced Depressive-Like Behaviors and Memory Deficits in Mice.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 48 citations in OpenAlex.
- Cilostazol as an adjunctive treatment in major depressive disorder: a pilot randomized, double-blind, and placebo-controlled clinical trial.Psychopharmacology · 2022Trial
- NDP-MSH rescues LPS-induced neuroinflammation, synaptic deficits, and depressive-like behaviors in mice: involvement of MC1R-cAMP/PKA signaling.Frontiers in pharmacology · 2026Article
- Novel, small molecules targeting the 5-HTbioRxiv : the preprint server for biology · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Effects of Qingyangshen glycosides on neuroplasticity in a mouse model of social defeat.Animal models and experimental medicine · 2025Article
- Phosphodiesterase 4 Inhibition in Neuropsychiatric Disorders Associated with Alzheimer's Disease.Cells · 2025Review
- Review
- BMAL1-Potential Player of Aberrant Stress Response in Q31L Mice Model of Affective Disorders: Pilot Results.International journal of molecular sciences · 2024Article
- Rolipram Ameliorates Memory Deficits and Depression-Like Behavior in APP/PS1/tau Triple Transgenic Mice: Involvement of Neuroinflammation and Apoptosis via cAMP Signaling.The international journal of neuropsychopharmacology · 2023Article
- Phosphodiesterase and psychiatric disorders: a two-sample Mendelian randomization study.Journal of translational medicine · 2023Article
- The Complexity and Multiplicity of the Specific cAMP Phosphodiesterase Family: PDE4, Open New Adapted Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Inhibition of phosphodiesterase-4 in the spinal dorsal horn ameliorates neuropathic pain via cAMP-cytokine-Cx43 signaling in mice.CNS neuroscience & therapeutics · 2022Article
- Effects of Chang-Kang-Fang Formula on the Microbiota-Gut-Brain Axis in Rats With Irritable Bowel Syndrome.Frontiers in pharmacology · 2022Article
- Neuroplasticity and Multilevel System of Connections Determine the Integrative Role of Nucleus Accumbens in the Brain Reward System.International journal of molecular sciences · 2021Review
- Protective Effect of Hydroxysafflor Yellow A against Chronic Mild Stress-induced Memory Impairments by Suppressing Tau Phosphorylation in Mice.Current medical science · 2021Article
- Article
- The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer's Disease: A Preclinical Study in APP/PS1 Transgenic Mice.The international journal of neuropsychopharmacology · 2020Article
- Forebrain overexpression of type 1 adenylyl cyclase promotes molecular stability and behavioral resilience to physical stress.Neurobiology of stress · 2020Article
- Dominant-Negative Attenuation of cAMP-Selective Phosphodiesterase PDE4D Action Affects Learning and Behavior.International journal of molecular sciences · 2020Article
- Inhibition of Phosphodiesterase 4 by FCPR03 Alleviates Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors and Prevents Dendritic Spine Loss in Mice Hippocampi.The international journal of neuropsychopharmacology · 2019Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphodiesterase 4 (PDE4) has four isoforms (PDE4A-D) with at least 25 splice variants. PDE4 subtype nonselective inhibitors produce potent antidepressant-like and cognition-enhancing effects via increased intracellular cyclic AMP (cAMP) signaling in the brain. Our previous data have demonstrated that long-form PDE4Ds appear to be involved in these pharmacological properties of PDE4 inhibitors in the normal animals. However, it is not clear whether long-form PDE4Ds are critical for the behaviors and related cellular signaling/neuronal plasticity/neuroendocrine alterations in the depressed animals. In the present study, animals exposed to the chronic unpredictable stress (CUS), a rodent model of depression, exhibited elevated corticosterone, depressive-like behavior, memory deficits, accompanied with decreased cAMP-PKA-CREB and cAMP-ERK1/2-CREB signaling and neuroplasticity. These alterations induced by CUS were reversed by RNA interference (RNAi)-mediated prefrontal cortex long-form PDE4Ds (especially PDE4D4 and PDE4D5) knock-down, similar to the effects of the PDE4 subtype nonselective inhibitor rolipram. Furthermore, these effects of RNAi were not enhanced by rolipram. These data indicate a predominant role of long-form PDE4Ds in the pharmacotherapies of PDE4 inhibitors for depression and concomitant memory deficits. Long-form PDE4Ds, especially PDE4D4 and PDE4D5, appear to be the promising targets for the development of antidepressants with high therapeutic indices.
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