Evidence mapPaperPMID 41219589Full record

ArticleClinical autonomic research : official journal of the Clinical Autonomic Research Society2026

α2δ-1-NMDAR1 complex in the hypothalamic paraventricular nucleus mediates anxiety-induced sympathetic hyperactivity.

Shaoru Zhang, Jia Tian, Bing Han, Hongyun Zhao, Moqing Zhou, Maria Jobran, Na Liu, Lin Yang, Wenyuan Wang, Cong Liu and 2 more

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Article in Clinical autonomic research : official journal of the Clinical Autonomic Research Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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5 · Who and what money

Authors and funding

12 authors.

Shaoru Zhang *Department of Neurology, Hebei Hospital, Xuanwu Hospital of Capital Medical University, Shijiazhuang, Hebei, China.
Jia Tian *Department of Neurology, Hebei Hospital, Xuanwu Hospital of Capital Medical University, Shijiazhuang, Hebei, China.
Bing HanDepartment of Neurology, Hebei Hospital, Xuanwu Hospital of Capital Medical University, Shijiazhuang, Hebei, China.
Hongyun ZhaoDepartment of Neurology, Hebei Hospital, Xuanwu Hospital of Capital Medical University, Shijiazhuang, Hebei, China.
Moqing ZhouDepartment of Neurology, Hebei Hospital, Xuanwu Hospital of Capital Medical University, Shijiazhuang, Hebei, China.
Maria JobranDepartment of Neurology, Hebei Hospital, Xuanwu Hospital of Capital Medical University, Shijiazhuang, Hebei, China.
Na LiuDepartment of Neurology, Hebei Hospital, Xuanwu Hospital of Capital Medical University, Shijiazhuang, Hebei, China.
Lin YangDepartment of Neurology, Hebei Hospital, Xuanwu Hospital of Capital Medical University, Shijiazhuang, Hebei, China.
Wenyuan WangDepartment of Neurology, Hebei Hospital, Xuanwu Hospital of Capital Medical University, Shijiazhuang, Hebei, China.
Cong LiuDepartment of Neurology, Hebei Hospital, Xuanwu Hospital of Capital Medical University, Shijiazhuang, Hebei, China.
Ming HuDepartment of Neurology, Hebei Hospital, Xuanwu Hospital of Capital Medical University, Shijiazhuang, Hebei, China. 58003730@hebmu.edu.cn.
Yanyong WangDepartment of Neurology, Hebei Hospital, Xuanwu Hospital of Capital Medical University, Shijiazhuang, Hebei, China. 57600267@hebmu.edu.cn.

Funding

Central Leading Local Science and Technology Development Fund Project (Basic research of free exploration) 236Z7733G
6 · The paper itself

Abstract

purposeTo explore changes in sympathetic nerve activity in anxiety, clarify mechanisms underlying increased sympathetic discharge, and evaluate an electrocardiogram (ECG)-derived high-frequency signal, termed skin sympathetic nerve activity (SKNA), as a potential noninvasive correlate of sympathetic outflow.

methodsMale Sprague-Dawley rats (n = 120) were divided into control and chronic unpredictable mild stress (CUMS) groups (n = 60 each). Anxiety-like behavior was assessed using the open field test and elevated plus maze. Stellate ganglion nerve activity (SGNA) and SKNA were recorded. The relationship between SGNA and SKNA was assessed in both time and frequency domains. The NMDAR1 inhibitor AP-5, Tat-fused α2δ-1 C-terminal peptide, or control peptide were microinjected into the hypothalamic paraventricular nucleus (PVN). PVN expression of GluN1 and α2δ-1 was analyzed via qPCR, western blotting, and co-immunoprecipitation. Plasma norepinephrine (NE) and corticosterone (CORT) levels were measured by ELISA.

resultsCUMS rats showed significant anxiety-like behaviors (reduced center time and open arm entries, p < 0.001), along with elevated SGNA and SKNA (p < 0.001). SGNA and SKNA were significantly correlated in the time domain (r = 0.538, p < 0.001) and showed strong concordance in their power spectral density (PSD) profiles, though not linear coherence. PVN GluN1 and α2δ-1 mRNA and protein levels were upregulated, with enhanced interaction. AP-5 and the Tat-fused α2δ-1 peptide normalized SGNA/SKNA in CUMS rats. No further reduction was seen when both were applied sequentially. Control peptide had no effect.

conclusionAnxiety increases sympathetic activity via upregulation of the PVN α2δ-1-NMDAR1 complex. SKNA is an ECG-derived high-frequency signal that correlates with SGNA under anesthesia and shows potential as a noninvasive index for sympathetic function in anxiety research.

Indexed as

AnxietyParaventricular Hypothalamic NucleusReceptors, N-Methyl-D-AspartateSympathetic Nervous SystemAnimalsMaleRatsRats, Sprague-DawleyStress, PsychologicalReceptors, N-Methyl-D-AspartateAnxietyECG-derived sympathetic index (SKNA)Paraventricular nucleusSympathetic nerve activityα2δ-1–NMDAR1 complex

Identifiers

PMID41219589

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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 Socratic graph.