Neurochemical Measurements in Animal Models of Neurodegeneration and Neurotoxicity
Abstract
This dissertation is a compilation of work in which selected analytical methods, including fast-scan cyclic voltammetry at carbon-fiber microelectrodes (FSCV), were used to determine neurotransmitter release and uptake properties in animals that model neurodegenerative disease and neurotoxicity. Alterations in the release and uptake of dopamine (DA), a central nervous system neurotransmitter that plays an important role in motor function and cognition, could contribute to, as well as be a consequence of, abnormal syndromes associated with neurodegeneration and neurotoxicity. First, we describe the application of FSCV to measure DA release and uptake in animals that model post chemotherapy cognitive impairment (PCCI). PCCI is a complication of chemotherapy treatment that is characterized by a general decline in cognition affecting visual and verbal memory, attention, complex problem solving skills, and motor function. It is estimated that one third of patients who undergo chemotherapy treatment will experience cognitive impairment. To investigate how chemotherapy treatment affects these systems, FSCV at carbon-fiber microelectrodes was used to measure dopamine release and uptake in coronal brain slices of the striatum. Here, we report on two PCCI studies with rats treated with carboplatin or a cocktail containing cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), both of which are composed of clinically relevant chemotherapeutic compounds. Measurements were taken from…
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