ORALS

SESSION: OxidativeTuePM1-R1	Ozawa International Symposium (3rd Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings)
Tue. 28 Nov. 2023 / Room: Dreams 1
Session Chairs: Christian Andre Amatore; Koji Fukui; Session Monitor: TBA

14:05: [OxidativeTuePM105] OS Plenary
DUAL-CHANNEL NANOELECTROCHEMICAL SENSOR FOR MONITORING SIMULTANEOUSLY INTRACELLULAR ROS AND NADH KINETIC VARIATIONS OF THEIR CONCENTRATIONS
Christian Andre Amatore¹ ; Wei-Hua Huang² ; Yu-Ting Jiao² ; Xiao-Ke Yang² ; Yu-Ting Qi² ; ¹CNRS & PSL, French Academy of Sciences, Paris, France; ²Wuhan University, Wuhan, China;
Paper Id: 177 [Abstract]

Reactive oxygen species (ROS) and nicotinamide adenine dinucleotide (NADH) are important intracellular redox-active molecules involved in various pathological processes including inflammation, neurodegenerative diseases, cancer, etc. However, their fast dynamic changes and mutual regulatory kinetic relationship during these biological processes were hard to simultaneously investigate intracellularly at single cells level. A dual-channel nanowire electrode integrating two conductive nanowires [1], one functionalized with platinum nanoparticles [2], and the other with conductive polymer [3], was nanofabricated to allow the selective and simultaneous real-time monitoring of intracellular ROS and NADH releases by mitochondria in single living MCF-7 tumoral cells stimulated by resveratrol. The release of ROS was observed to occur a few tenths of a second before that of NADH. Beyond the importance of such an information impossible to acquire by other means, this work established the feasibility of simultaneously monitoring two intracellular species and their kinetics relationships over sub-second time scales. It is expected that this concept will benefit to a deeper understanding of mutual regulatory relationship between crucial intracellular molecular markers during physiological and pathological processes as well as for evaluating medical treatments.The authors would like to acknowledge support from joint sino-french CNRS IRP NanoBioCatEchem. CA thanks Xiamen University for his Distinguished Visiting Professor position.

References:
[1] Y.T. Jiao, H. Jiang, W.T. Wu, Y.T. Qi, M.Y. Wen, X.K. Yang, Y.R. Kang, X.W. Zhang, C. Amatore, W.H. Huang. Biosensors and Bioelectronics, 2023, 222, 114928.
[2] H. Jiang, X.W. Zhang, Q.L. Liao, W.T. Wu, Y.L. Liu, W.H. Huang. Small, 2019, 15, 1901787.
[3] H. Jiang, Y.T. Qi, W.T. Wu, M.Y. Wen, Y.L. Liu, W.H. Huang. Chem. Sci., 2020, 11, 8771.

SESSION: OxidativeTuePM2-R1	Ozawa International Symposium (3rd Intl. Symp. on Oxidative Stress for Sustainable Development of Human Beings)
Tue. 28 Nov. 2023 / Room: Dreams 1
Session Chairs: Fuhua Yang; Christian Andre Amatore; Session Monitor: TBA

16:00: [OxidativeTuePM209] OS Plenary
ALZHEIMER DISEASE: NANOELECTROCHEMISTRY REVEALS HOW SOLUBLE Aβ42 OLIGOMERS ALTER VESICULAR STORAGE AND RELEASE OF GLUTAMATE
Christian Andre Amatore¹ ; Wei-Hua Huang² ; Xiao-Ke Yang² ; Fu-Li Zhang² ; Xue-Ke Jin² ; Yu-Ting Jiao² ; Yan-Ling Liu² ; ¹CNRS & PSL, French Academy of Sciences, Paris, France; ²Wuhan University, Wuhan, China;
Paper Id: 181 [Abstract]

Glutamate (Glu) is one of the most important excitatory transmitter in the nervous system. Impairment of its vesicular release due to β-amyloid (Aβ) oligomers liberation in the brain is thought to participate in pathological processes leading to Alzheimer’s disease. However, before this work [1] it was unclear whether soluble Aβ42 oligomers affect intravesicular amounts of Glu or its release in the brain, or both.
Nanoelectrochemical measurements which will be presented used amperometric nanowire Glu biosensors to test single Glu-generating neuronal varicosities. This revealed that soluble Aβ42 oligomers first caused a dramatic increase in vesicular Glu storage and stimulation-induced release, accompanied by a high level of parallel spontaneous exocytosis. This was shown to ultimately result in the depletion of intravesicular Glu content enforcing greatly reduced Glu release.
Molecular biology tools and mouse models of Aβ amyloidosis have further established that the transient hyperexcitation observed during the primary pathological stage was mediated by an altered behavior of VGLUT1 responsible for transporting Glu into synaptic vesicles. Thereafter, an overexpression of Vps10p-tail-interactor-1a, a protein that maintains spontaneous release of neurotransmitters by selective interaction with t-SNAREs, resulted in a depletion of intravesicular Glu content, triggering advanced-stage neuronal malfunction. These findings are expected to open perspectives for remediating Aβ42-induced neuronal hyperactivity and neuronal degeneration in the context of initiation of Alzheimer disease. The authors would like to acknowledge support from joint sino-french CNRS IRP NanoBioCatEchem. CA thanks Xiamen University for his Distinguished Visiting Professor position.

References:
1. Xiao-Ke Yang, Fu-Li Zhang, Xue-Ke Jin, Yu-Ting Jiao, Xin-Wei Zhang, Yan-Ling Liu, Christian Amatore, Wei-Hua Huang. Nanoelectrochemistry reveals how soluble Aβ42 oligomers alter vesicular storage and release of glutamate. Proc. Nat. Acad. Sci. USA 120 (2023) e2219994120.