Elucidating the Cognitive Deficits following Doxorubicin treatment
Type of Degreethesis
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Chemotherapeutic drugs are effective in the treatment of various types of tumors; however, the optimal clinical effectiveness is limited due to secondary effects including cognitive impairment, also known as “chemobrain”, which refers to a phenomenon in which cancer survivors exhibit cognitive impairment following chemotherapy. The present study investigated the effects of doxorubicin on cognitive impairment through its effects on α-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-glutamate receptor expression and function. To achieve this aim, long-term potentiation (LTP), a cellular model of memory and the function as well as expression of AMPA receptors were assessed. Results indicate that doxorubicin treated animals showed impaired LTP and AMPA receptor channel function. In addition, AMPAR subunit GluR1, brain-derived neurotrophic factor (BDNF), and α-stargazin expression were significantly decreased, whereas GluR2 subunit expression significantly increased in doxorubicin treated animals compared to controls. Therefore, we conclude that doxorubicin induces cognitive impairment by modulating glutamatergic system.
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