ArticleFrontiers in aging neuroscience2018
Inhibition of Phosphodiesterase-4 Reverses Aβ-Induced Memory Impairment by Regulation of HPA Axis Related cAMP Signaling.
Article in Frontiers in aging neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 52 citations in OpenAlex.
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- Elucidating the Neurobiological Underpinnings of Mild Behavioral Impairment in Tauopathies: Clinical and Molecular Insights.International journal of molecular sciences · 2026Review
- Alcohol drinking is attenuated by PDE4 inhibition but partial microglia depletion is not sufficient to block stress-induced escalation of alcohol intake in female mice.Alcohol (Fayetteville, N.Y.) · 2025Article
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- Maternal upbringing and selective breeding for voluntary exercise behavior modify patterns of DNA methylation and expression of genes in the mouse brain.Genes, brain, and behavior · 2023Article
- 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
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- Drug Discovery and Development Targeting Dementia.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Involvement of brain-derived neurotrophic factor signaling in the pathogenesis of stress-related brain diseases.Frontiers in molecular neuroscience · 2023Review
- Mechanisms Involved in Microglial-Interceded Alzheimer's Disease and Nanocarrier-Based Treatment Approaches.Journal of personalized medicine · 2021Review
- Roflumilast and tadalafil improve learning and memory deficits in intracerebroventricular Aβ1-42 rat model of Alzheimer's disease through modulations of hippocampal cAMP/cGMP/BDNF signaling pathway.Pharmacological reports : PR · 2021Article
- METTL3-dependent RNA mMolecular neurodegeneration · 2021Article
- Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders.Molecular psychiatry · 2021Review
- Beta amyloid-induced time-dependent learning and memory impairment: involvement of HPA axis dysfunction.Metabolic brain disease · 2020Article
- Cilomilast Ameliorates Renal Tubulointerstitial Fibrosis by Inhibiting the TGF-β1-Smad2/3 Signaling Pathway.Frontiers in medicine · 2020Article
- Neurogenic effect of exercise via the thioredoxin-1/ extracellular regulated kinase/β-catenin signaling pathway mediated by β2-adrenergic receptors in chronically stressed dentate gyrus.Journal of exercise nutrition & biochemistry · 2019Article
- Pharmacological Targeting of Microglial Activation: New Therapeutic Approach.Frontiers in cellular neuroscience · 2019Review
- Modified Huang-Lian-Jie-Du Decoction Ameliorates AOxidative medicine and cellular longevity · 2019Article
- Phosphodiesterase-2 Inhibitor Bay 60-7550 Ameliorates Aβ-Induced Cognitive and Memory Impairment via Regulation of the HPA Axis.Frontiers in cellular neuroscience · 2019Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Beta amyloid peptides (Aβ) are found to be associated with dysfunction of hypothalamic-pituitary-adrenal axis (HPA axis) that leads to memory and cognitive deficits in patients with Alzheimer's disease (AD). Phosphodiesterase 4 (PDE4) inhibitors increase the intracellular cAMP activities, which may ameliorate cognitive deficits associated with AD. However, it remains unclear whether PDE4-mediated reversal of cognitive impairment in mouse model of AD is related to HPA axis and downstream cAMP-dependent pathway. The present study investigated the effects of PDE4 inhibitor rolipram on Aβ1-42-induced cognitive dysfunction and its underlying mechanisms. The step-down passive avoidance (PA) and Morris water-maze (MWM) tests were conducted 1 week (1 W), 2 months (2 M), and 6 months (6 M) after intracerebroventricular microjection (i.c.v.) of Aβ1-42. The results suggested that memory impairment emerged as early as 1 W, peaked at 2 M, and lasted until 6 M after injection. Chronic treatment with rolipram (0.1, 0.5, 1.0 mg/kg/d, i.p.) for 2 weeks (i.e., treatment started at 1.5 months after Aβ1-42 microinjection) dose-dependently improved memory performance in both MWM and PA tests. Moreover, rolipram reversed the Aβ-induced increases in serum corticosterone (CORT), corticotropin-releasing factor, and glucocorticoid receptors (CRF-R and GR) levels, whereas it decreases in brain-derived neurotropic factor (BDNF) and the ratio of pCREB to CREB expression. These effects of rolipram were prevented by pre-treatment with PKA inhibitor H89. The findings indicated that the protective effects of rolipram against Aβ1-42-induced memory deficits might involve HPA axis and cAMP-CREB-BDNF signaling.
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