Behavioral Neuroscience

National Institute On Aging

Investigators

Linked publications & trials

Abstract

Projects initiated earlier under BNS and published as full-length papers during the reporting period include studies in mouse models examining the influence of cytokine activation on brainstem catecholamine systems relevant to Parkinsons disease (Mouton et al., 2010). Another investigation targeting mechanisms of neurodegeneration used an in vitro assay to document that adiponectin receptor mediated signaling confers protection against cytotoxicity induced by kainic acid treatment in cultured hippocampal neurons (Qiu et al., 2011). A final series of experiments, just accepted for publication, extended earlier work in BNS exploring the cognitive effects of chemotherapy treatment in a rat model. By comparison with corresponding studies in humans, this approach allowed assessment of chemotherapy effects on learning and memory per se, independent of the influence of cancer itself or comorbid factors such as depression. In this investigation we documented the long term learning and memory effects of a chemotherapy cocktail used widely in the treatment of breast cancer in women, consisting of 5-fluorouracil (5FU) and cyclophosphamide (CYP). Cognitive function was assessed across an extensive test battery administered 2 months following repeated drug treatment, well after acute toxicity had substantially resolved, at a point comparable to when some patients report the development of chemofog symptoms. Against a background of substantial weight loss and mortality in our rat model, however, neither low or high doses of the CYP/5FU cocktail affected any of the cognitive measures examined, including retrograde fear memory, and new learning and memory for spatial information (Long et al., in press). These findings add to a growing literature suggesting that learning and memory processes mediated by the hippocampus can be relatively resistant to chemotherapy. No further studies in this area are currently planned in LEG.