Science Advances
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2024
·Vol. 10
·期 49
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IF 11.7
Chaoyue Gu,Fanzhen Kong,Sen Liang,Xiang Zhao,Bingjie Kong,Tianhe Jiang,Jianan Yu,Qi Li,Yuqing Lin,Shuo Bai,Yuanhua Shao
Chloride ion, a pivotal cerebral anion involved in neuronal inhibition, is implicated in various neurodegenerative diseases. Conventional direct faradaic detection based on electron transfers at solid electrode/solution interfaces has been proven ineffective due to the electrochemically inactive nature of Cl−. Here, we present an approach involving molecularly tailored liquid/liquid interfacial ultramicro iontronics (L/L-UIs) supported at ultramicropipettes filled with organic gel containing lipophilic bis-thioureas ionophores, which represents the first application of amperometric methodology based on electrochemical facilitated ion transfers reactions at a soft L/L ultramicrointerface to achieve in vivo sensing of electrochemically inactive ions, and dynamically tracking cerebral Cl− in vivo. Furthermore, evidence of dynamic neuronal Cl− regulation via KCC2 modulated through GABAB receptors was provided, further substantiating GABAB receptor–mediated Cl−-related neuronal inhibition. The proposed L/L-UIs have notable potential for in situ tracking of other crucial electrochemically inactive ions or ionized biomolecules in vivo, thereby facilitating the study of brain diseases and the diagnosis and treatment of related disorders.
研究领域:
神经科学
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生物医学工程
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分析化学
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DOI
PubMed
高影响因子
Nature Nanotechnology
·
2023
·
IF 38.3
Zuo Yanming,Ye Jingjia,Cai Wanxiong,Guo Binjie,Chen Xiangfeng,Lin Lingmin,Jin Shuang,Zheng Hanyu,Fang Ao,Qian Xingran,Abdelrahman Zeinab,Wang Zhiping,Zhang Zhipeng,Chen Zuobin,Yu Bin,Gu Xiaosong,Wang Xuhua
Despite considerable unmet medical needs, effective pharmacological treatments that promote functional recovery after spinal cord injury remain limited. Although multiple pathological events are implicated in spinal cord injuries, the development of a microinvasive pharmacological approach that simultaneously targets the different mechanisms involved in spinal cord injury remains a formidable challenge. Here we report the development of a microinvasive nanodrug delivery system that consists of amphiphilic copolymers responsive to reactive oxygen species and an encapsulated neurotransmitter-conjugated KCC2 agonist. Upon intravenous administration, the nanodrugs enter the injured spinal cord due to a disruption in the blood–spinal cord barrier and disassembly due to damage-triggered reactive oxygen species. The nanodrugs exhibit dual functions in the injured spinal cord: scavenging accumulated reactive oxygen species in the lesion, thereby protecting spared tissues, and facilitating the integration of spared circuits into the host spinal cord through targeted modulation of inhibitory neurons. This microinvasive treatment leads to notable functional recovery in rats with contusive spinal cord injury.
研究领域:
神经科学
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药理学
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纳米技术
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DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2023
·
IF 4.7
Yihan Yu,Dandan Tian,Sanghyok Ri,Tongchol Kim,Kwangjin Ju,Jiongming Zhang,Shuangshuang Teng,Weixia Zhang,Wei Shi,Guangxu Liu
Although accumulating data demonstrated that gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter , plays an important regulatory role in immunity of vertebrates, its immunomodulatory function and mechanisms of action remain poorly understood in invertebrates such as bivalve mollusks . In this study, the effect of GABA on phagocytic activity of hemocytes was evaluated in a commercial bivalve species, Tegillarca granosa . Furthermore, the potential regulatory mechanism underpinning was investigated by assessing potential downstream targets. Data obtained demonstrated that in vitro GABA incubation significantly constrained the phagocytic activity of hemocytes. In addition, the GABA-induced suppression of phagocytosis was markedly relieved by blocking of GABA A and GABA B receptors using corresponding antagonists. Hemocytes incubated with lipopolysaccharides (LPS) and GABA had significant higher K + -Cl - cotransporter 2 (KCC2) content compared to the control. In addition, GABA treatment led to an elevation in intracellular Cl − , which was shown to be leveled down to normal by blocking the ionotropic GABA A receptor. Treatment with GABA A receptor antagonist also rescued the suppression of GABA A receptor-associated protein ( GABARAP ), KCC , TNF receptor associated factor 6 ( TRAF6 ), inhibitor of nuclear factor kappa-B kinase subunit alpha ( IKKα ), and nuclear factor kappa B subunit 1 ( NFκB ) caused by GABA incubation. Furthermore, incubation of hemocytes with GABA resulted in a decrease in cAMP content, an increase in intracellular Ca 2+ , and downregulation of cAMP-dependent protein kinase ( PKA ), calmodulin kinase II ( CAMK2 ), calmodulin ( CaM ), calcineurin ( CaN ), TRAF6 , IKKα , and NFκB . All these above-mentioned changes were found to be evidently relieved by blocking the metabotropic G-protein-coupled GABA B receptor. Our results suggest GABA may play an inhibitory role on phagocytosis through binding to both GABA A and GABA B receptors, and subsequently regulating corresponding downstream pathways in bivalve invertebrates.
研究领域:
免疫学
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分子生物学
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海洋生物学
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无脊椎动物生理学
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DOI
PubMed
高影响因子
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