Harpagide, a natural product, promotes synaptic vesicle release as measured by nanoelectrode amperometry

Tang, Yun; Yang, Xiaoke; Zhang, Xinwei; Wu, Wentao; Zhang, Fuli; Jiang, Hong; Liu, Yanling; Amatore, Christian; Huang, Wei‐Hua

doi:10.1039/c9sc05538j

Cited by 42 publications

(23 citation statements)

References 59 publications

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“…Because overactivated microglia cells are known to cause inflammatory response which is a key player in PD, and harpagide is suggested to possess anti‐inflammatory effects to reduce the overproduction of neuronal peroxides in agreement with our observations. [ 23 ] Therefore, we want to further investigate the neuroprotective effect of hapagide under vivo‐like (DA neurons‐microglia co‐culture) environment. The coimmunostain by TH (DA neuronal marker, green), CD11b/c (microglial marker, especially for the activated microglia, red) and Hoechst (cell nucleus marker) in Figure S2 indicated the successful culture of DAergic neurons and microglia in co‐cultured system.…”

Section: Resultsmentioning

confidence: 99%

“…[ 18‐21 ] It has been shown that harpagide can facilitate axon regeneration of injured DAergic neurons, and maintain neurotransmitter dopamine (DA) release by reducing ROS level in injured neurons. [ 22‐23 ] However, in real pathological process, the initial factor of PD neuronal injury is nerve inflammation caused by microglial activation and the consequent neuron loss. It remains unknown whether harpagide protects neurons from inflammation‐mediated injury by inhibiting microglial activation.…”

Section: Background and Originality Contentmentioning

confidence: 99%

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Harpagide Inhibits Microglial Activation and Protects Dopaminergic Neurons as Revealed by Nanoelectrode Amperometry^†

et al. 2021

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Parkinson's disease (PD) is one of the most common neurogenerative diseases (NDDs), characterized as less neurotransmitter release and loss of dopaminergic (DAergic) neurons with microglial inflammatory response as a key player. Natural product harpagide with anti-inflammatory function is a potential therapeutic drug of PD, but its role towards microglial activation and inflammation-mediated neuronal injury remained unsure. In this work, taking advantage of nanoelectrode amperometry with high temporal-spatial resolution, we used nanowire electrodes (NWEs) to monitor intracellular reactive oxygen species (ROS) level and carbon fiber nanoelectrodes (CFNEs) to detect synaptic dopamine exocytosis, to explore the effect of harpagide in modulating microglial inflammatory reaction and protecting DAergic neurons in neuron-microglia co-culture system. The results indicate that harpagide inhibits microglia from activation induced by LPS/IFN-γ and generation of ROS, therefore reduces inflammation-mediated neural injury and maintains dopamine exocytosis function. These conclusions establish that harpagide possesses promising avenues for preventive or therapeutic interventions against PD and other NDDs.

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Section: Resultsmentioning

confidence: 99%

Section: Background and Originality Contentmentioning

confidence: 99%

Harpagide Inhibits Microglial Activation and Protects Dopaminergic Neurons as Revealed by Nanoelectrode Amperometry^†

et al. 2021

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“…Furthermore, the postsynaptic potential was successfully monitored with a glass nanopipette electrode, which again indicated that SCG-SMC synapses built in a microchip functioned effectively. This unique approach offers a platform to understand the true nature of neuronal exocytosis and the effect of drugs or chemicals, for example, harpagide, on it (Tang et al, 2020 ).…”

Section: Single-cell Amperometry For Monitoring Neurotransmitter Relementioning

confidence: 99%

Recent Progress in Quantitatively Monitoring Vesicular Neurotransmitter Release and Storage With Micro/Nanoelectrodes

Liu

Wang

et al. 2021

Front. Chem.

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Exocytosis is one of the essential steps for chemical signal transmission between neurons. In this process, vesicles dock and fuse with the plasma membrane and release the stored neurotransmitters through fusion pores into the extracellular space, and all of these steps are governed with various molecules, such as proteins, ions, and even lipids. Quantitatively monitoring vesicular neurotransmitter release in exocytosis and initial neurotransmitter storage in individual vesicles is significant for the study of chemical signal transmission of the central nervous system (CNS) and neurological diseases. Electrochemistry with micro/nanoelectrodes exhibits great spatial–temporal resolution and high sensitivity. It can be used to examine the exocytotic kinetics from the aspect of neurotransmitters and quantify the neurotransmitter storage in individual vesicles. In this review, we first introduce the recent advances of single-cell amperometry (SCA) and the nanoscale interface between two immiscible electrolyte solutions (nanoITIES), which can monitor the quantity and release the kinetics of electrochemically and non-electrochemically active neurotransmitters, respectively. Then, the development and application of the vesicle impact electrochemical cytometry (VIEC) and intracellular vesicle impact electrochemical cytometry (IVIEC) and their combination with other advanced techniques can further explain the mechanism of neurotransmitter storage in vesicles before exocytosis. It has been proved that these electrochemical techniques have great potential in the field of neuroscience.

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“…Tang et al used carbon fiber nanoelectrodes (CFNEs) to monitor exocytotic events occurring inside single dopaminergic synapses. 4 They showed that the natural product, harpagide, managed to enhance synaptic DA release and restore DA release at normal levels from injured neurons in a Parkinson’s disease model by inhibiting ROS-induced phosphorylation and aggregation of α-synuclein.…”

Section: Electrochemical Analysis Of Single Cells and Organellesmentioning

confidence: 99%

Chemical Analysis of Single Cells and Organelles

Nguyen

Rabasco

et al. 2020

Anal. Chem.

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Harpagide, a natural product, promotes synaptic vesicle release as measured by nanoelectrode amperometry

Abstract: Nanoelectrode amperometry was used to monitor DA release inside single DAergic synapses, and demonstrated that harpagide effectively enhances synaptic DA release by reducing intracellular ROS generation and inhibiting α-Syn phosphorylation.

Cited by 42 publications

References 59 publications

Harpagide Inhibits Microglial Activation and Protects Dopaminergic Neurons as Revealed by Nanoelectrode Amperometry^†

Harpagide Inhibits Microglial Activation and Protects Dopaminergic Neurons as Revealed by Nanoelectrode Amperometry^†

Recent Progress in Quantitatively Monitoring Vesicular Neurotransmitter Release and Storage With Micro/Nanoelectrodes

Chemical Analysis of Single Cells and Organelles

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Harpagide, a natural product, promotes synaptic vesicle release as measured by nanoelectrode amperometry

Abstract: Nanoelectrode amperometry was used to monitor DA release inside single DAergic synapses, and demonstrated that harpagide effectively enhances synaptic DA release by reducing intracellular ROS generation and inhibiting α-Syn phosphorylation.

Cited by 42 publications

References 59 publications

Harpagide Inhibits Microglial Activation and Protects Dopaminergic Neurons as Revealed by Nanoelectrode Amperometry†

Harpagide Inhibits Microglial Activation and Protects Dopaminergic Neurons as Revealed by Nanoelectrode Amperometry†

Recent Progress in Quantitatively Monitoring Vesicular Neurotransmitter Release and Storage With Micro/Nanoelectrodes

Chemical Analysis of Single Cells and Organelles

Contact Info

Product

Resources

About

Harpagide Inhibits Microglial Activation and Protects Dopaminergic Neurons as Revealed by Nanoelectrode Amperometry^†

Harpagide Inhibits Microglial Activation and Protects Dopaminergic Neurons as Revealed by Nanoelectrode Amperometry^†