ArticleThe international journal of neuropsychopharmacology2023
Rolipram Ameliorates Memory Deficits and Depression-Like Behavior in APP/PS1/tau Triple Transgenic Mice: Involvement of Neuroinflammation and Apoptosis via cAMP Signaling.
Article in The international journal of neuropsychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Meta-Analysis and Topological Perturbation in Interactomic Network for Antiopioid Addiction Drug Repurposing.Journal of chemical information and modeling · 2025Pooled it
- Molecular and neural circuit mechanisms of parvalbumin (PV) neurons in depression: Insights and advances.iScience · 2026Review
- Repurposing apremilast for alzheimer's disease: multitarget modulation of cAMP‑PI3K/Akt-GSK‑3β and NF‑κB signaling.Metabolic brain disease · 2026Review
- Emerging Molecular Targets and Recent Advancements for the Management of Depression.Molecular neurobiology · 2026Review
- PDE4A knockdown rescues alcohol-induced cognitive impairment and synaptic dysfunction via the cAMP/PKA/CREB pathway.The international journal of neuropsychopharmacology · 2026Article
- Elucidating the Neurobiological Underpinnings of Mild Behavioral Impairment in Tauopathies: Clinical and Molecular Insights.International journal of molecular sciences · 2026Review
- Smart Drug-Delivery Approaches for Enhanced Management of Comorbid Conditions in Alzheimer's Disease.Life (Basel, Switzerland) · 2026Review
- Inhibition of PDE4 Alleviates Endoplasmic Reticulum Stress and Neuronal Damage via Activation of Nrf2/HO-1 in Parkinson's Disease.Molecular neurobiology · 2025Article
- Cognitive improvement effects of PF-04957325, a phosphodiesterase-8 inhibitor, in mouse models of Alzheimer's disease via modulating neuroinflammation.The international journal of neuropsychopharmacology · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Inhibition of PDE4B ameliorates cognitive defects in the model of alcoholic dementia in 3xTg-AD mice via PDE4B/cAMP/PKA signaling.The international journal of neuropsychopharmacology · 2025Article
- Promoting proteostasis by cAMP/PKA and cGMP/PKG.Trends in molecular medicine · 2025Review
- Connecting dots: Preclinical foundations to clinical realities of PDE4 inhibitors in Alzheimer's disease.Inflammopharmacology · 2025Review
- Phosphodiesterase 4 Inhibition in Neuropsychiatric Disorders Associated with Alzheimer's Disease.Cells · 2025Review
- Conventional and Emerging Drug Targeting Sites in Alzheimer's Disease and the Role of Translational Informatics in its Diagnosis and Management.Current neuropharmacology · 2025Review
- New progress on the role and mechanism of tau protein in Alzheimer's disease and depression.Frontiers in neurology · 2025Review
- Pharmacological characterization and preclinical evaluation of 11h: a novel, brain-penetrant PDE4 inhibitor for neurological disorders.Frontiers in pharmacology · 2025Article
- Protective effect of PDE4B subtype-specific inhibition in an App knock-in mouse model for Alzheimer's disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Phosphodiesterase 8 (PDE8): Distribution and Cellular Expression and Association with Alzheimer's Disease.Neurochemical research · 2024Article
- Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlzheimer disease (AD) and depression often cooccur, and inhibition of phosphodiesterase-4 (PDE4) has been shown to ameliorate neurodegenerative illness. Therefore, we explored whether PDE4 inhibitor rolipram might also improve the symptoms of comorbid AD and depression.
methodsAPP/PS1/tau mice (10 months old) were treated with or without daily i.p. injections of rolipram for 10 days. The animal groups were compared in behavioral tests related to learning, memory, anxiety, and depression. Neurochemical measures were conducted to explore the underlying mechanism of rolipram.
resultsRolipram attenuated cognitive decline as well as anxiety- and depression-like behaviors. These benefits were attributed at least partly to the downregulation of amyloid-β, Amyloid precursor protein (APP), and Presenilin 1 (PS1); lower tau phosphorylation; greater neuronal survival; and normalized glial cell function following rolipram treatment. In addition, rolipram upregulated B-cell lymphoma-2 (Bcl-2) and downregulated Bcl-2-associated X protein (Bax) to reduce apoptosis; it also downregulated interleukin-1β, interleukin-6, and tumor necrosis factor-α to restrain neuroinflammation. Furthermore, rolipram increased cAMP, PKA, 26S proteasome, EPAC2, and phosphorylation of ERK1/2 while decreasing EPAC1.
conclusionsRolipram may mitigate cognitive deficits and depression-like behavior by reducing amyloid-β pathology, tau phosphorylation, neuroinflammation, and apoptosis. These effects may be mediated by stimulating cAMP/PKA/26S and cAMP/exchange protein directly activated by cAMP (EPAC)/ERK signaling pathways. This study suggests that PDE4 inhibitor rolipram can be an effective target for treatment of comorbid AD and depression.
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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.