Age-Related Intraneuronal Elevation of αII-Spectrin Breakdown Product SBDP120 in Rodent Forebrain Accelerates in 3×Tg-AD Mice

Spectrins line the intracellular surface of plasmalemma and play a critical role in supporting cytoskeletal stability and flexibility. Spectrins can be proteolytically degraded by calpains and caspases, yielding breakdown products (SBDPs) of various molecular sizes, with SBDP120 being largely derived from caspase-3 cleavage. SBDPs are putative biomarkers for traumatic brain injury. The levels of SBDPs also elevate in the brain during aging and perhaps in Alzheimer’s disease (AD), although the cellular basis for this change is currently unclear. Here we examined age-related SBDP120 alteration in forebrain neurons in rats and in the triple transgenic model of AD (3×Tg-AD) relative to non-transgenic controls. SBDP120 immunoreactivity (IR) was found in cortical neuronal somata in aged rats, and was prominent in the proximal dendrites of the olfactory bulb mitral cells. Western blot and densitometric analyses in wild-type mice revealed an age-related elevation of intraneuronal SBDP120 in the forebrain which was more robust in their 3×Tg-AD counterparts. The intraneuronal SBDP120 occurrence was not spatiotemporally correlated with transgenic amyloid precursor protein (APP) expression, β-amyloid plaque development, or phosphorylated tau expression over various forebrain regions or lamina. No microscopically detectable in situ activated caspase-3 was found in the nuclei of SBDP120-containing neurons. The present study demonstrates the age-dependent intraneuronal presence of an αII-spectrin cleavage fragment in mammalian forebrain which is exacerbated in a transgenic model of AD. This novel neuronal alteration indicates that impairments in membrane protein metabolism, possibly due to neuronal calcium mishandling and/or enhancement of calcium sensitive proteolysis, occur during aging and in transgenic AD mice

Numerical simulation of the limiting current for the CE mechanism at a microdisc electrode

The finite difference method in conjunction with a conformal mapping technique is used to simulate the diffusion limiting current for three different CE mechanisms at a microdisc electrode. Working surfaces are presented for the variation of the limiting current with a normalised homogeneous kinetic parameter and equilibrium constant. Empirical equations are given to describe the current when the homogeneous equilibrium position lies heavily in favour of the electroinactive species. © 2007 Elsevier B.V. All rights reserved

Measuring the size distribution of microelectrodes in an array

Microdisc arrays are considered for which the constituent disc electrodes are nonuniform in size. A method is described for using linear sweep voltammetry to calibrate the array to find the mean and standard deviation of the microdisc radii. Numerical simulation is used to model linear sweep voltammetry at arrays of single-sized microdiscs and of nonuniformly sized microdiscs. © 2007 Elsevier B.V. All rights reserved

Influence of electrode roughness on cyclic voltammetry

Electrodes with rough surfaces are of great practical importance from both applied and fundamental points of view. The diffusion domain approach is used to model cyclic voltammetry at such electrodes. Electrode roughness only has a significant effect on the shape of cyclic voltammograms and peak currents at relatively high values of electrode roughness. To verify the theory two experimental systems were used: TMPD in acetonitrile and Ru(NH3) 6Cl3 in aqueous solution. In both cases cyclic voltammograms on the flat and roughened glassy carbon electrodes were in agreement with theory. Even significant surface roughness produced by deliberate polishing or scratching is not sufficient to be distinguished in cyclic voltammetry experiments conducted under the usual conditions. © 2008 American Chemical Society

Linear sweep voltammetry at the tubular electrode: Theory of EC2 mechanisms

Concentration profiles are obtained via numerical solution for the species involved in an EC2 mechanism in a tubular flow cell. Voltammetric waves are simulated and the variation of the half-wave potential as a function of the kinetic parameters is explored. Criteria are presented for the analysis of expected current/voltage curves

Theory of diffusion to an "annular microband" electrode

The finite difference method is used to perform 2D numerical simulation of chronoamperometry and voltammetry at a hypothesised "annular microband" (AMB) electrode. The diffusional properties of this electrode system are inferred from the results of simulations and are found to be highly efficient. Comparison is drawn with infinite limiting cases of the geometry, which are shown not to support mass-transport limited steady-state diffusion, whereas the AMB supports such a steady state. Lastly, the optimisation of the geometry is discussed in the context of the experimental application of voltammetry as a means to investigate rapid electrochemical kinetics. © 2008 Elsevier B.V. All rights reserved

Voltammetry at nanoparticle and microparticle modified electrodes: Theory and experiment

Electrodes modified with random arrays of nanoparticles and/or microparticles find significant application in electroanalysis. Theory is developed for the diffusional current at nanoparticle-modified electrodes via the diffusion domain approach which is used to model the electrode surface as a randomly distributed assembly of spherical particles. Experiments are reported for the electrocatalytic reduction of protons at a palladium particle modified electrode and shown to behave as predicted theoretically. © 2007 American Chemical Society

Cathodic reduction of bisulfite and sulfur dioxide in aqueous solutions on copper electrodes: an electrochemical ESR study.

The electrochemical reduction of aqueous solutions of sulfite under acidic conditions on copper electrodes is reported, and a mechanism is proposed. Cyclic voltammetry at a copper disk suggests the operation of two reduction processes, the dominant process depending on solution pH. At very low pH (0-2), sulfur dioxide is reduced in a two-electron, two-proton reaction, but at higher pH (2-5), bisulfite is the electroactive species, being reduced by a single electron to ultimately yield the SO2*- radical anion. Simultaneous electrochemical electron spin resonance (ESR) measurements using a tubular flow cell support this proposal, and suggest that the radical anion is in equilibrium with dithionite, which is found to decay at low pH. Digisim modeling of the system is shown to be consistent with this mechanism over the experimental pH range

Chemical instability promotes apparent electrochemical irreversibility: Studies on the electrode kinetics of the one electron reduction of the 2,6-diphenylpyrylium cation in acetonitrile solution

Concentration profiles are obtained via numerical solution for the species involved in EC and EC2 mechanisms in a tubular flow cell. Voltammetric waves are simulated and the effect of the kinetic parameters on the waveshape is studied by considering the mass transport corrected Tafel slope. It is demonstrated that, when coupled to a follow up homogeneous step with sufficiently fast kinetics, a fast electron transfer may appear electrochemically irreversible in terms of its Tafel gradient. The electrochemical reduction of 2,6-diphenylpyrylium fluoroborate in acetonitrile solution is studied at a gold flow cell. Simulation of the recorded data permits us to infer a value of 1-2.5 × 10-3 cm s-1 for the standard electrochemical rate constant for the 2,6-diphenylpyrylium cation/radical couple. © 2006 Elsevier B.V. All rights reserved

Fabricating random arrays of boron doped diamond nano-disc electrodes: Towards achieving maximum Faradaic current with minimum capacitive charging

We report the first construction of a random array of boron doped diamond (BDD) nano-disc electrodes (RAN BDD), formed by a simple three-step method. First molybdenum(IV) dioxide nanoparticles are electrodeposited onto a BDD substrate. Second the electrode surface is covered in an insulating polymer film by the electropolymerization of a 4-nitrophenyldiazonium salt. Third the molybdenum dioxide nanoparticles are dissolved from the BDD surface (removing the polymer layer directly above them only) using dilute hydrochloric acid to expose nano-discs of BDD, ca. 20 ± 10 nm in diameter surrounded by a polymer insulating the remainder of the BDD. This method produces up to 650 ± 25 million BDD nano-disc electrodes per cm2. Various RAN BDD electrodes were produced using this method with a similar distribution of nano-disc size and number density, confirming that this is a reliable and reproducible method of manufacturing such nanoelectrode arrays. At modest scan rates the RAN BDD array was found to produce peak currents approaching that of the Randles-Ševčík limit for the equivalent geometric electrode area despite the fact that most of the surface was insulated by the polymer as shown by voltammetry and atomic force microscopy. The experimental results are compared with simulations of both ordered and random arrays of nano-disc electrodes, the results of which demonstrate that the maximum current obtainable at such arrays is that predicted by the Randles-Ševčík equation. The array of BDD nano-discs shows a significantly reduced capacitive background current compared to the bare BDD electrode, suggesting that such devices may offer improved signal resolution in electroanalytical measurements. © 2008 Elsevier B.V. All rights reserved