The Extracellular Zn2+ Concentration Surrounding Excited Neurons Is High Enough to Bind Amyloid‐β Revealed by a Nanowire Transistor. Issue 24 (16th May 2018)

• Record Type: Journal Article
• Authors: Anand, Ankur; Chi, Chih‐Hung; Banerjee, Subhasree; Chou, Ming‐Yi; Tseng, Fan‐Gang; Pan, Chien‐Yuan; Chen, Yit‐Tsong
• Is Part Of: Small. Volume 14:Issue 24(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-05-16
• Subjects: AMPA receptor -- amyloid‐β -- extracellular zinc concentration -- field‐effect transistors -- neurodegeneration; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.201704439
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: The Zn 2+ stored in the secretory vesicles of glutamatergic neurons is coreleased with glutamate upon stimulation, resulting in the elevation of extracellular Zn 2+ concentration ( C Z n 2 + e x ). This elevation of C Z n 2 + e x regulates the neurotransmission and facilitates the fibrilization of amyloid‐β (Aβ). However, the exact C Z n 2 + e x surrounding neurons under (patho)physiological conditions is not clear and the connection between C Z n 2 + e x and the Aβ fibrilization remains obscure. Here, a silicon nanowire field‐effect transistor (SiNW‐FET) with the Zn 2+ ‐sensitive fluorophore, FluoZin‐3 (FZ‐3), to quantify the C Z n 2 + e x in real time is modified. This FZ‐3/SiNW‐FET device has a dissociation constant of ≈12 × 10 −9 m against Zn 2+ . By placing a coverslip seeded with cultured embryonic cortical neurons atop an FZ‐3/SiNW‐FET, the C Z n 2 + e x elevated to ≈110 × 10 −9 m upon stimulation with α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA). Blockers against the AMPA receptor or exocytosis greatly suppress this elevation, indicating that the Zn 2+ stored in the synaptic vesicles is the major source responsible for this elevation of C Z n 2 + e x . In addition, a SiNW‐FET modified with Aβ could bind Zn 2+ with a dissociation constant of ≈633 × 10 −9 m and respond to the Zn 2+ released from AMPA‐stimulated neurons. Therefore, the C Z n 2 + e x can reach a level high enough to bind Aβ and the Zn 2+ homeostasis can be a therapeutic strategy to prevent neurodegeneration. Abstract : A novel design to monitor the extracellular Zn 2+ concentration in real‐time is presented. A silicon nanowire field‐effect transistor with a Zn 2+ chelator or amyloid‐β to detect the Zn 2+ coreleased with neurotransmitters from the vesicles of cultured cortical neurons is modified. These results support the formation of Zn 2+ ‐amyloid‐β plaque, one of the most risky factors for neurodegeneration, under pathophysiological conditions.