ArticleNeurobiology of learning and memory2018
A negative allosteric modulator of PDE4D enhances learning after traumatic brain injury.
Article in Neurobiology of learning and memory, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- The effects of the PDE4 inhibitor roflumilast on cognitive performance after a cerebrovascular accident: a double-blind randomized placebo-controlled trial with an open label extension (ROSTMEMA).Journal of psychopharmacology (Oxford, England) · 2026Trial
- Astroglial TNFR2 signaling regulates hippocampal synaptic function and plasticity in a sex dependent manner.Brain, behavior, and immunity · 2025Article
- Targeted protein degradation of PDE4 shortforms by a novel proteolysis targeting chimera.The FEBS journal · 2025Article
- Review
- Targeting phosphodiesterase 4 as a potential therapy for Parkinson's disease: a review.Molecular biology reports · 2024Review
- Phosphodiesterase-4 Inhibition in Parkinson's Disease: Molecular Insights and Therapeutic Potential.Cellular and molecular neurobiology · 2023Review
- 3D printing of injury-preconditioned secretome/collagen/heparan sulfate scaffolds for neurological recovery after traumatic brain injury in rats.Stem cell research & therapy · 2022Article
- Novel Synthetic and Natural Therapies for Traumatic Brain Injury.Current neuropharmacology · 2021Review
- Dominant-Negative Attenuation of cAMP-Selective Phosphodiesterase PDE4D Action Affects Learning and Behavior.International journal of molecular sciences · 2020Article
- A Mechanistic Rationale for PDE-4 Inhibitors to Treat Residual Cognitive Deficits in Acquired Brain Injury.Current neuropharmacology · 2020Review
- Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.Nature reviews. Drug discovery · 2019Review
- Article
- Article
- Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases.Frontiers in pharmacology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Traumatic brain injury (TBI) significantly decreases cyclic AMP (cAMP) signaling which produces long-term synaptic plasticity deficits and chronic learning and memory impairments. Phosphodiesterase 4 (PDE4) is a major family of cAMP hydrolyzing enzymes in the brain and of the four PDE4 subtypes, PDE4D in particular has been found to be involved in memory formation. Although most PDE4 inhibitors target all PDE4 subtypes, PDE4D can be targeted with a selective, negative allosteric modulator, D159687. In this study, we hypothesized that treating animals with D159687 could reverse the cognitive deficits caused by TBI. To test this hypothesis, adult male Sprague Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. After 3 months of recovery, animals were treated with D159687 (0.3 mg/kg, intraperitoneally) at 30 min prior to cue and contextual fear conditioning, acquisition in the water maze or during a spatial working memory task. Treatment with D159687 had no significant effect on these behavioral tasks in non-injured, sham animals, but did reverse the learning and memory deficits in chronic TBI animals. Assessment of hippocampal slices at 3 months post-TBI revealed that D159687 reversed both the depression in basal synaptic transmission in area CA1 as well as the late-phase of long-term potentiation. These results demonstrate that a negative allosteric modulator of PDE4D may be a potential therapeutic to improve chronic cognitive dysfunction following TBI.
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Registered trials
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