ArticleFrontiers in neuroanatomy2020
Mapping Phosphodiesterase 4D (PDE4D) in Macaque Dorsolateral Prefrontal Cortex: Postsynaptic Compartmentalization in Layer III Pyramidal Cell Circuits.
Article in Frontiers in neuroanatomy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Decoding and reconstructing disease relations between dry eye and depression: a multimodal investigation comprising meta-analysis, genetic pathways and Mendelian randomization.Journal of advanced research · 2025Pooled it
- Dorsolateral Prefrontal Cortex Circuitry at the Intersection of Cognition and Disease.Biological psychiatry · 2026Review
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- Dysregulated calcium signaling in the aged macaque entorhinal cortex associated with tau hyperphosphorylation.Frontiers in aging neuroscience · 2025Article
- Dysregulated calcium signaling in the aged primate association cortices: vulnerability to Alzheimer's disease neuropathology.Frontiers in aging neuroscience · 2025Review
- Genomic variations associated with risk and protection against vincristine-induced peripheral neuropathy in pediatric cancer patients.NPJ genomic medicine · 2024Article
- Identification of important gene signatures in schizophrenia through feature fusion and genetic algorithm.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- Nanoscale imaging of pT217-tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early-stage neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Phosphodiesterase 4D activity in acrodysostosis-associated neural pathology: too much or too little?Brain communications · 2024Review
- Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer's disease.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Interrogating the Etiology of Sporadic Alzheimer's Disease Using Aging Rhesus Macaques: Cellular, Molecular, and Cortical Circuitry Perspectives.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- Ablation of specific long PDE4D isoforms increases neurite elongation and conveys protection against amyloid-β pathology.Cellular and molecular life sciences : CMLS · 2023Article
- Unusual Molecular Regulation of Dorsolateral Prefrontal Cortex Layer III Synapses Increases Vulnerability to Genetic and Environmental Insults in Schizophrenia.Biological psychiatry · 2022Review
- The Variation of Transcriptomic Perturbations is Associated with the Development and Progression of Various Diseases.Disease markers · 2022Article
- Studies of aging nonhuman primates illuminate the etiology of early-stage Alzheimer's-like neuropathology: An evolutionary perspective.American journal of primatology · 2021Review
- The genie in the bottle-magnified calcium signaling in dorsolateral prefrontal cortex.Molecular psychiatry · 2021Review
- Age-related calcium dysregulation linked with tau pathology and impaired cognition in non-human primates.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates.Frontiers in aging neuroscience · 2021Article
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7 authors at 2 institutions in 1 country.
Funding
Abstract
cAMP signaling has powerful, negative effects on cognitive functions of the primate dorsolateral prefrontal cortex (dlPFC), opening potassium channels to reduce firing and impair working memory, and increasing tau phosphorylation in aging neurons. This contrasts with cAMP actions in classic circuits, where it enhances plasticity and transmitter release. PDE4 isozymes regulate cAMP actions, and thus have been a focus of research and drug discovery. Previous work has focused on the localization of PDE4A and PDE4B in dlPFC, but PDE4D is also of great interest, as it is the predominant PDE4 isoform in primate association cortex, and PDE4D expression decreases with aging in human dlPFC. Here we used laser-capture microdissection transcriptomics and found that PDE4D message is enriched in pyramidal cells compared to GABAergic PV-interneurons in layer III of the human dlPFC. A parallel study in rhesus macaques using high-spatial resolution immunoelectron microscopy revealed the ultrastructural locations of PDE4D in primate dlPFC with clarity not possible in human post-mortem tissue. PDE4D was especially prominent in dendrites associated with microtubules, mitochondria, and likely smooth endoplasmic reticulum (SER). There was substantial postsynaptic labeling in dendritic spines, associated with the SER spine-apparatus near glutamatergic-like axospinous synapses, but sparse labeling in axon terminals. We also observed dense PDE4D labeling perisynaptically in astroglial leaflets ensheathing glutamatergic connections. These data suggest that PDE4D is strategically positioned to regulate cAMP signaling in dlPFC glutamatergic synapses and circuits, especially in postsynaptic compartments where it is localized to influence cAMP actions on intracellular trafficking, mitochondrial physiology, and internal calcium release.
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