Label-Free Electrochemical Biosensor for Monitoring of Chloride Ion in an Animal Model of Alzhemier’s Disease

The potential damage of Alzheimer’s disease (AD) in brain function has attracted extensive attention. As the most common anion, Cl^- has been indicated to play significant roles in brain diseases, particularly in the pathological process of AD. In this work, a label-free selective and accurate electrochemical biosensor was first developed for real-time monitoring of Cl^- levels in a mouse brain model of AD and rat brain upon global cerebral ischemia. Silver nanoparticles (AgNPs) were designed and synthesized as selective recognition element for Cl^-, while 5′-MB-GGCGCGATTTT-SH-3′ (SH-DNA-MB, MB = methylene blue) was selected as an inner reference molecule for a built-in correction to avoid the effects from the complicated brain. The electrochemical biosensor showed high accuracy and remarkable selectivity for determination of Cl^- over other anions, metal ions, amino acids, and other biomolecules. Furthermore, three-dimensional nanostructures composed of single-walled carbon nanotubes (SWNTs) and Au nanoleaves were assembled on the carbon fiber microelectrode (CFME) surface to enhance the response signal. Finally, the developed biosensor with high analytical performance, as well as the unique characteristic of CFME itself including inertness in live brain and good biocompatibility, was successfully applied to in vivo determination of Cl^- levels in three brain regions: striatum, hippocampus, and cortex of live mouse and rat brains. The comparison of average levels of Cl^- in normal striatum, hippocampus, and cortex of normal mouse brains and those in the mouse model brains of AD was reported. In addition, the results in rat brains followed by cerebral ischemia demonstrated that the concentrations of Cl^- decreased by 19.8 ± 0.5% (n = 5) in the striatum and 27.2 ± 0.3% (n = 5) in hippocampus after cerebral ischemia for 30 min, but that negligible change in Cl^- concentration was observed in cortex.