ArticleMolecular psychiatry2021
Increased surface P2X4 receptor regulates anxiety and memory in P2X4 internalization-defective knock-in mice.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Medial Olivocochlear Efferent Modulation of Cochlear Micromechanics Requires P2X4 Receptor in Outer Hair Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Plasma Proteomic Profiling of a Group of Anxious Dogs by LC-MS/MS: A Case-Control Study.Proteomics. Clinical applications · 2025Article
- Role of HDAC5 Epigenetics in Chronic Craniofacial Neuropathic Pain.International journal of molecular sciences · 2024Review
- Elucidating the mechanisms underlying astrocyte-microglia crosstalk in hippocampal neuroinflammation induced by acute diquat exposure.Environmental science and pollution research international · 2024Article
- The neurobiological mechanisms and therapeutic prospect of extracellular ATP in depression.CNS neuroscience & therapeutics · 2024Review
- Different localization of P2X4 and P2X7 receptors in native mouse lung - lack of evidence for a direct P2X4-P2X7 receptor interaction.Frontiers in immunology · 2024Article
- Microglial P2X4 receptors are essential for spinal neurons hyperexcitability and tactile allodynia in male and female neuropathic mice.iScience · 2023Article
- Increased Synaptic ATP Release and CD73-Mediated Formation of Extracellular Adenosine in the Control of Behavioral and Electrophysiological Modifications Caused by Chronic Stress.ACS chemical neuroscience · 2023Article
- Increased ATP Release and Higher Impact of Adenosine AMolecular neurobiology · 2023Article
- Article
- Structure-Activity Relationship and Neuroprotective Activity of 1,5-Dihydro-2Journal of medicinal chemistry · 2022Article
- The Purinergic System as a Target for the Development of Treatments for Bipolar Disorder.CNS drugs · 2022Review
- Increased surface P2X4 receptors by mutant SOD1 proteins contribute to ALS pathogenesis in SOD1-G93A mice.Cellular and molecular life sciences : CMLS · 2022Article
- The P2X4 Receptor: Cellular and Molecular Characteristics of a Promising Neuroinflammatory Target.International journal of molecular sciences · 2022Review
- The Role of Microglial Purinergic Receptors in Pain Signaling.Molecules (Basel, Switzerland) · 2022Review
- Microglial Activation Modulated by P2X4R in Ischemia and Repercussions in Alzheimer's Disease.Frontiers in physiology · 2022Review
- P2X7 Receptors and TMEM16 Channels Are Functionally Coupled with Implications for Macropore Formation and Current Facilitation.International journal of molecular sciences · 2021Article
- Contribution of P2X4 receptor in pain associated with rheumatoid arthritis: a review.Purinergic signalling · 2021Review
- Resveratrol-enhanced SIRT1-mediated osteogenesis in porous endplates attenuates low back pain and anxiety behaviors.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Update of P2X receptor properties and their pharmacology: IUPHAR Review 30.British journal of pharmacology · 2021Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ATP signaling and surface P2X4 receptors are upregulated selectively in neurons and/or glia in various CNS disorders including anxiety, chronic pain, epilepsy, ischemia, and neurodegenerative diseases. However, the cell-specific functions of P2X4 in pathological contexts remain elusive. To elucidate P2X4 functions, we created a conditional transgenic knock-in P2X4 mouse line (Floxed P2X4mCherryIN) allowing the Cre activity-dependent genetic swapping of the internalization motif of P2X4 by the fluorescent mCherry protein to prevent constitutive endocytosis of P2X4. By combining molecular, cellular, electrophysiological, and behavioral approaches, we characterized two distinct knock-in mouse lines expressing noninternalized P2X4mCherryIN either exclusively in excitatory forebrain neurons or in all cells natively expressing P2X4. The genetic substitution of wild-type P2X4 by noninternalized P2X4mCherryIN in both knock-in mouse models did not alter the sparse distribution and subcellular localization of P2X4 but increased the number of P2X4 receptors at the surface of the targeted cells mimicking the pathological increased surface P2X4 state. Increased surface P2X4 density in the hippocampus of knock-in mice altered LTP and LTD plasticity phenomena at CA1 synapses without affecting basal excitatory transmission. Moreover, these cellular events translated into anxiolytic effects and deficits in spatial memory. Our results show that increased surface density of neuronal P2X4 contributes to synaptic deficits and alterations in anxiety and memory functions consistent with the implication of P2X4 in neuropsychiatric and neurodegenerative disorders. Furthermore, these conditional P2X4mCherryIN knock-in mice will allow exploring the cell-specific roles of P2X4 in various physiological and pathological contexts.
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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.