Evidence map›Paper›PMID 40776395›Full record

ArticleCNS neuroscience & therapeutics2025

Kapβ2 Reverses Sevoflurane-Induced Hydrogel Phase Transition of hnRNPA2/B1-SG in Hypoxic Primary Rat Hippocampal Neurons.

Miao Zhang, Xinyi Wang, Feiyu Jia, Chenyi Yang, Zixuan Wang, Huihui Liao, Lin Zhang, Xi Xin, Haiyun Wang

Abstract read
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Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Miao ZhangThe Third Central Clinical College of Tianjin Medical University, Tianjin, China.ORCID 0009-0003-2510-2150
Xinyi WangNankai University Affinity the Third Central Hospital, Tianjin, China.
Feiyu JiaThe Third Central Clinical College of Tianjin Medical University, Tianjin, China.ORCID 0009-0002-6336-6977
Chenyi YangNankai University Affinity the Third Central Hospital, Tianjin, China.ORCID 0000-0002-7299-3668
Zixuan WangThe Third Central Clinical College of Tianjin Medical University, Tianjin, China.
Huihui LiaoThe Third Central Clinical College of Tianjin Medical University, Tianjin, China.
Lin ZhangThe Third Central Clinical College of Tianjin Medical University, Tianjin, China.
Xi XinNankai University Affinity the Third Central Hospital, Tianjin, China.
Haiyun WangThe Third Central Clinical College of Tianjin Medical University, Tianjin, China.ORCID 0000-0002-0084-2342

Funding

the National Natural Science Foundation of China 82071220the National Natural Science Foundation of China 82371205Tianjin Health Research Project TJWJ2023QN042Tianjin Health Research Project TJWJ2023XK019Tianjin key Medical Discipline (Specialty) Construction Project TJYXZDXK-072C
6 · The paper itself

Abstract

aimsSevoflurane can aggravate the progression of neurodegeneration, although the underlying mechanisms remain incompletely understood. Our previous study identified a link between heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) and sevoflurane-induced neurocognitive impairments. The abnormal hydrogel phase transition of stress granules (SGs) assembled via liquid-liquid phase separation (LLPS) by hnRNPA2/B1 is a crucial element in neurodegeneration. Karyopherin-β2 (Kapβ2) is known to specifically recognize hnRNPA2/B1 and reverses the hydrogel transition of SGs. This study aimed to elucidate the mechanistic role of hnRNPA2/B1-SG phase transition in sevoflurane-induced hippocampal neuronal dysfunction under hypoxic conditions, and to determine whether Kapβ2 can mitigate these effects.

methodsUsing a hypoxic primary rat hippocampal neuron model and Kapβ2 overexpression, we investigated the effects of sevoflurane on hnRNPA2/B1 expression and subcellular distribution, phase separation dynamics, and the liquid-to-solid transition of hnRNPA2/B1-associated SGs. We also assessed neuronal function and cognitive protein expression. Experimental approaches included Western blotting, RT-qPCR, immunofluorescence staining, and fluorescence recovery after photobleaching (FRAP).

resultsIn hypoxic hippocampal neurons, sevoflurane altered the nuclear-to-cytoplasmic distribution of hnRNPA2/B1, promoted abnormal LLPS, and facilitated the formation of irreversible solid-phase hnRNPA2/B1-containing SGs. These changes were associated with neuronal dysfunction and reduced expression of cognition-related proteins. Kapβ2 overexpression disrupted these aggregates, restored the dynamic reversibility of hnRNPA2/B1 LLPS, reversed the sevoflurane-induced hydrogel phase transition of hnRNPA2/B1-SGs, and enhanced the expression of cognition-related proteins.

conclusionThe hydrogel phase transition of hnRNPA2/B1-SG is a key pathological mechanism of sevoflurane-induced hippocampal neuronal injury. Kapβ2 may serve as a potential therapeutic target to counteract sevoflurane-related neurotoxicity.

Indexed as

Anesthetics, InhalationHeterogeneous-Nuclear Ribonucleoprotein Group A-BHippocampusNeuronsSevofluraneStress GranulesAnimalsCell HypoxiaCells, CulturedHydrogelsPhase TransitionRatsRats, Sprague-DawleyAnesthetics, InhalationHeterogeneous-Nuclear Ribonucleoprotein Group A-BhnRNP A2HydrogelsSevofluranehnRNPA2/B1hydrogel phase transitionhypoxic hippocampal neuronsKapβ2neurodegenerative disorderssevofluranestress granules

Identifiers

PMID40776395
PMCPMC12331528

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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.