| dc.description.abstract | Hydrogen peroxide is a membrane-permeable reactive oxygen species (ROS) and a neuromodulator. Here, we enhanced the electrochemical detection of hydrogen peroxide by modifying a carbon-fiber microelectrode by dip-coating in slurry consisting of graphene, a conductive material with a honeycomb structure, and electrochemically depositing Nafion, a fluoropolymer. Morphological characterization of the modified electrode by scanning electron microscopy (SEM) revealed a fine coating of Nafion/graphene at the electrode surface and elemental mapping by energy dispersive X-ray spectroscopy indicated the presence of oxide groups, characteristic of graphene. Flow injection analysis of hydrogen peroxide using this modified electrode revealed a 5.3-fold increase in the oxidation signal compared the unmodified electrode. Moreover, the electrode kinetics were similar to those observed with bare carbon-fiber microelectrodes. These results suggest that this electrode may be useful for detection of transient hydrogen peroxide concentrations in biological systems. Post-chemotherapy cognitive impairment (PCCI), also known as ‘chemo brain’, is a decline in cognitive function experienced by patients who have undergone chemotherapy treatment. Recent studies have shown that up to 30% - 70% of patients who receive chemotherapy treatment suffer from a general decline in complex problem solving, memory, learning, and motor function. Previous studies in our group have revealed that dopamine release and uptake, evoked in the striatum by electrical stimulation and measured with fast-scan cyclic voltammetry at carbon-fiber microelectrodes (FSCV), is are impaired as a result of chemotherapy treatment. Although the reasons underlying this decrease in release are not clear, it is possible that terminals may be damaged by ROS. Hydrogen peroxide is an important ROS that has the potential to not only cause cellular damage, but also is a participant in the regulation of dopamine (DA) release. It is also known to be an inter- and intra-cellular signaling molecule. In the striatum H2O2 is generated from glutamatergic AMPA receptor activation in medium spiny neurons. H2O2 can inhibit DA neuron firing via activation of ATP sensitive K+ (KATP) channels. Furthermore an imbalance of H2O2 generation and metabolism can cause neurodegeneration. To investigate the role of hydrogen peroxide in chemo brain, we measured sub-second changes in hydrogen peroxide levels with FSCV in striatal brain slices from rats received receiving chemotherapy and Saline treated rats. We utilized two common chemotherapeutic agents, Carboplatin and 5-fluorouracil (5FU). We found that, upon treatment of slices with mercaptosuccinate, an inhibitor of glutathione peroxidase, the frequency of occurrence and the magnitude of transient increases in hydrogen peroxide levels were greater in carboplatin-treated rats compared to Saline control rats. | |
