2016
DOI: 10.18632/aging.100920 View full text |Buy / Rent full text
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Abstract: Recent research shows that chemotherapy agents can be more toxic to healthy brain cells than to the target cancer cells. They cause a range of side effects, including memory loss and cognitive dysfunction that can persist long after the completion of treatment. This condition is known as chemo brain. The molecular and cellular mechanisms of chemo brain remain obscure. Here, we analyzed the effects of two cytotoxic chemotherapy drugs—cyclophosphamide (CPP) and mitomycin C (MMC) - on transcriptomic and epigeneti… Show more

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“…These results may bear relevance in the context of counteracting the side effects of Mitomycin C chemotherapy. It is known that Mitomycin C leads to oxidative DNA damage and decreases global DNA methylation in a sex-specific pattern in mice; it is also known that most of the changes induced by chemotherapy in the pre-frontal cortex of female mice are similar to those occurring during the brain's ageing (80). Considering the effects of Mitomycin C on phage r1t gene expression, it could be hypothesized that chemotherapy also alters the balance between phages and Lactococci in the microbiota, with consequences on the functions regulated by the microbiota and, in particular, on the immune system.…”
Section: Discussionmentioning
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“…These results may bear relevance in the context of counteracting the side effects of Mitomycin C chemotherapy. It is known that Mitomycin C leads to oxidative DNA damage and decreases global DNA methylation in a sex-specific pattern in mice; it is also known that most of the changes induced by chemotherapy in the pre-frontal cortex of female mice are similar to those occurring during the brain's ageing (80). Considering the effects of Mitomycin C on phage r1t gene expression, it could be hypothesized that chemotherapy also alters the balance between phages and Lactococci in the microbiota, with consequences on the functions regulated by the microbiota and, in particular, on the immune system.…”
Section: Discussionmentioning
“…35 We dissected the molecular mechanisms of chemo brain by using a murine model, and we analyzed epigenetic and gene expression changes in the hippocampus and PFC tissues of mice 24 hours and 3 weeks after treatment with cytotoxic chemotherapy agents mitomycin C (MMC) and cyclophosphomade (CPP), 2 agents that have been shown to cause chemo brain; however, the mechanisms of their effects remained elusive. 31 Our data showed that MMC and CPP treatments lead to drug-, sex-, and brain region-specific and persistent changes in global gene expression profiles. Overall, gene expression responses were much more profound for MCC than CPP exposure, and they were most prominent in the PFC tissues of female animals 3 weeks after MMC treatment, affecting pathways responsible for oxidative stress and other effects.…”
Section: New Insights Into Mechanisms Of Chemo Brainmentioning
“…[26][27][28] Epigenetic changes play key roles in brain and behavior. 29,30 In a recent pioneer study in Aging (2016) 31 we have proposed a new theory of chemo brain in which the mechanisms that underlie the neurotoxic side effects of chemotherapy on the brain are epigenetically regulated and associated with altered gene expression. 31 Our analysis focused on the hippocampus and prefrontal cortex (PFC) and was based on their pivotal roles in memory, learning, and executive functions.…”
Section: New Insights Into Mechanisms Of Chemo Brainmentioning
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“…Epigenetic changes that underlie aberrant gene expression patterns have been well-documented in breast cancer literature. Recently, we analysed the molecular mechanisms of chemo brain [ 14 ] by investigating the gene expression profiles in the prefrontal cortex (PFC) and hippocampus (HPC) of mice 3 weeks after treatment with the cytotoxic chemotherapy agents mitomycin C (MMC) and cyclophosphamide (CPP) [ 14 ]. We showed that chemotherapy altered gene expression profiles in the PFC and HPC tissues; the changes were most prominent in the PFC tissues of females 3 weeks after MMC treatment.…”
Section: Introductionmentioning