TY - JOUR
T1 - Infusion of etoposide in the CA1 disrupts hippocampal immediate early gene expression and hippocampus-dependent learning
AU - Boutros, Sydney Weber
AU - Kessler, Kat
AU - Unni, Vivek K.
AU - Raber, Jacob
N1 - Funding Information:
This work was partially supported by a Tartar Trust Fellowship, an OHSU SOM Pilot Fund, an NSF Graduate Research Fellowship award, NASA NSCOR G-00066-4, R21 CA223461, R21 AG065914, NS102227, F31 AG067629, Knight CVP-003, and the development accounts of Drs. Unni and Raber.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Tight regulation of immediate early gene (IEG) expression is important for synaptic plasticity, learning, and memory. Recent work has suggested that DNA double strand breaks (DSBs) may have an adaptive role in post-mitotic cells to induce IEG expression. Physiological activity in cultured neurons as well as behavioral training leads to increased DSBs and subsequent IEG expression. Additionally, infusion of etoposide—a common cancer treatment that induces DSBs—impairs trace fear memory. Here, we assessed the effects of hippocampal infusion of 60 ng of etoposide on IEG expression, learning, and memory in 3–4 month-old C57Bl/6J mice. Etoposide altered expression of the immediate early genes cFos and Arc in the hippocampus and impaired hippocampus-dependent contextual fear memory. These data add to the growing evidence that DSBs play an important role in IEG expression, learning, and memory, opening avenues for developing novel treatment strategies for memory-related disorders.
AB - Tight regulation of immediate early gene (IEG) expression is important for synaptic plasticity, learning, and memory. Recent work has suggested that DNA double strand breaks (DSBs) may have an adaptive role in post-mitotic cells to induce IEG expression. Physiological activity in cultured neurons as well as behavioral training leads to increased DSBs and subsequent IEG expression. Additionally, infusion of etoposide—a common cancer treatment that induces DSBs—impairs trace fear memory. Here, we assessed the effects of hippocampal infusion of 60 ng of etoposide on IEG expression, learning, and memory in 3–4 month-old C57Bl/6J mice. Etoposide altered expression of the immediate early genes cFos and Arc in the hippocampus and impaired hippocampus-dependent contextual fear memory. These data add to the growing evidence that DSBs play an important role in IEG expression, learning, and memory, opening avenues for developing novel treatment strategies for memory-related disorders.
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U2 - 10.1038/s41598-022-17052-y
DO - 10.1038/s41598-022-17052-y
M3 - Article
C2 - 35896679
AN - SCOPUS:85135062117
SN - 2045-2322
VL - 12
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 12834
ER -