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Chemotherapy Agents and the Inhibition of Neuronal Birthing in the Brain - The Cause of Chemo Brain

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Final rept. 1 Apr 2003-14 Oct 2006

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Patients undergoing chemotherapy can experience a decline in cognitive abilities. While well described from a clinical perspective, little is known of the neurological substrate for this difficulty, commonly known as chemo brain. We hypothesize that the cognitive difficulties experienced by patients undergoing chemotherapy are the result of impaired neurogenesis, especially in the hippocampus. We further hypothesize that agents that do not cross the blood-brain barrier will not show reduced rates of neurogenesis, in contrast to agents that readily cross into the central nervous system CNS. Our objective is to compare the effect of drugs that enter the CNS Cytoxan and 5-FU with agents that do not Adriamycin and Taxol with respect to their ability to impair the birthing of new neurons in the hippocampus of adult mice. By testing whether chemotherapeutic agents that enter the CNS can reduce neurogenesis, we hope to develop an animal model of chemo brain that will allow further studies. Furthermore, if we can show that inhibition of neurogenesis is a correlate of behavioral decline after chemotherapy, we will have provided evidence that modification of chemotherapeutic regimens specifically, using strategies to prevent CNS entry of drugs would be of great importance in improving the quality of life in cancer patients.

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  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

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