ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2021
α2δ-1-Dependent NMDA Receptor Activity in the Hypothalamus Is an Effector of Genetic-Environment Interactions That Drive Persistent Hypertension.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Astrocyte-Neuron Crosstalk in Hypertension: Mechanisms and Therapeutic Significance.Reviews in cardiovascular medicine · 2026Review
- Molecular Partners of Voltage-Gated Calcium Channel β and αThe Journal of membrane biology · 2026Review
- Chloride homeostasis dysfunction drives hyperactivation of corticotropin-releasing factor-expressing neurons in the amygdala in stress-induced hypertension.The Journal of clinical investigation · 2026Article
- α2δ-1-NMDAR1 complex in the hypothalamic paraventricular nucleus mediates anxiety-induced sympathetic hyperactivity.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026Article
- From peripheral initiation to central integration: a narrative review of the antihypertensive mechanisms of acupuncture in regulating autonomic nervous system homeostasis.Frontiers in neuroscience · 2026Review
- RCAN1-Mediated Calcineurin Impairment Drives Sympathetic Outflow in Hypertension.Circulation research · 2025Article
- Regulation of L-Lactate in Glutamate Excitotoxicity Under Cerebral Ischemia: Pathophysiology and Preventive Strategy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- α2δ-1-Linked NMDA and AMPA Receptors in Neuropathic Pain and Gabapentinoid Action.Journal of neurochemistry · 2025Review
- The impact of long-term isolation on anxiety, depressive-like and social behavior in aging Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) male rats.Scientific reports · 2024Article
- Effect of Short-Term Restraint Stress on the Expression of Genes Associated with the Response to Oxidative Stress in the Hypothalamus of Hypertensive ISIAH and Normotensive WAG Rats.Antioxidants (Basel, Switzerland) · 2024Article
- Quercetin alleviates chronic unpredictable mild stress-induced depression-like behavior by inhibiting NMDAR1 with α2δ-1 in rats.CNS neuroscience & therapeutics · 2024Article
- DNA demethylation in the hypothalamus promotes transcription of Agtr1a and Slc12a2 and hypertension development.The Journal of biological chemistry · 2024Article
- A neural perspective on the treatment of hypertension: the neurological network excitation and inhibition (E/I) imbalance in hypertension.Frontiers in cardiovascular medicine · 2024Review
- Article
- α2δ-1 as a New Target for Immunosuppressant-Induced Hypertension.Circulation research · 2023Article
- Brain α2δ-1-Bound NMDA Receptors Drive Calcineurin Inhibitor-Induced Hypertension.Circulation research · 2023Article
- mGluR5 from Primary Sensory Neurons Promotes Opioid-Induced Hyperalgesia and Tolerance by Interacting with and Potentiating Synaptic NMDA Receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Corticotropin-releasing hormone neurons in the central nucleus of amygdala are required for chronic stress-induced hypertension.Cardiovascular research · 2023Article
- The α2δ-1-NMDA receptor complex and its potential as a therapeutic target for ischemic stroke.Frontiers in neurology · 2023Review
- α2δ-1 protein drives opioid-induced conditioned reward and synaptic NMDA receptor hyperactivity in the nucleus accumbens.Journal of neurochemistry · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The interplay between genetic and environmental factors is critically involved in hypertension development. The paraventricular nucleus (PVN) of the hypothalamus regulates sympathetic output during stress responses and chronic hypertension. In this study, we determined mechanisms of synaptic plasticity in the PVN in chronic stress-induced persistent hypertension in male borderline hypertensive rats (BHR), the first offspring of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. In Wistar-Kyoto rats, chronic unpredictable mild stress (CUMS) increased arterial blood pressure (ABP) and heart rate, which quickly returned to baseline after CUMS ended. In contrast, in BHR, CUMS caused persistent elevation in ABP, which lasted at least 2 weeks after CUMS ended. CUMS also increased the mRNA level of α2δ-1 and synaptic protein levels of GluN1, α2δ-1, and α2δ-1-GluN1 complexes in the PVN in BHR. Furthermore, CUMS significantly increased the frequency of miniature EPSCs and the amplitude of NMDAR currents in spinally projecting PVN neurons in BHR; these increases were normalized by blocking NMDARs with AP5, inhibiting α2δ-1 with gabapentin, or disrupting the α2δ-1-NMDAR interaction with α2δ-1Tat peptide. Microinjection of AP5 or α2δ-1Tat peptide into the PVN normalized elevated ABP and renal sympathetic nerve activity in stressed BHR. In addition, systemically administered gabapentin or memantine attenuated higher ABP induced by CUMS in BHR. Our findings indicate that chronic stress-induced persistent hypertension is mediated by augmented sympathetic outflow via α2δ-1-bound NMDARs in the PVN. This new information provides a cellular and molecular basis for how the genetic-environment interactions cause persistent hypertension.
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Registered trials
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.