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.
| Long, Jeffrey M; Lee, Garrick D; Kelley-Bell, Bennett et al. (2011) Preserved learning and memory following 5-fluorouracil and cyclophosphamide treatment in rats. Pharmacol Biochem Behav 100:205-11 |
| Qiu, Guang; Wan, Ruiqian; Hu, Jingping et al. (2011) Adiponectin protects rat hippocampal neurons against excitotoxicity. Age (Dordr) 33:155-65 |
| Pistell, Paul J; Nelson, Chris M; Miller, Marshall G et al. (2009) Striatal lesions interfere with acquisition of a complex maze task in rats. Behav Brain Res 197:138-43 |
| Mouton, Peter R; Chachich, Mark E; Quigley, Christopher et al. (2009) Caloric restriction attenuates amyloid deposition in middle-aged dtg APP/PS1 mice. Neurosci Lett 464:184-7 |
| Ahmet, Ismayil; Spangler, Edward; Shukitt-Hale, Barbara et al. (2009) Blueberry-enriched diet protects rat heart from ischemic damage. PLoS One 4:e5954 |
| Stranahan, Alexis M; Lee, Kim; Pistell, Paul J et al. (2008) Accelerated cognitive aging in diabetic rats is prevented by lowering corticosterone levels. Neurobiol Learn Mem 90:479-83 |
| Shukitt-Hale, Barbara; Lau, Francis C; Carey, Amanda N et al. (2008) Blueberry polyphenols attenuate kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus. Nutr Neurosci 11:172-82 |
