1. Entorhinal Cortex Circuit Dysfunction in Mouse Models of APOE4 and Chemotherapy‐Induced Cognitive Impairment.
- Author
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Luo, Nancy, Vicini, Stefano, and Rebeck, Bill
- Abstract
Background: APOE4 has broad effects, one of which is worsened cognitive outcomes in cancer survivors following chemotherapy treatment compared to APOE3. Method: 1‐2 month old female APOE3 and APOE4‐Targeted Replacement (TR) mice were used for whole cell patch‐clamp experiments in the entorhinal cortex. Chemotherapy was introduced via a single injection of doxorubicin (10 mg/kg) or saline (control) and treated APOE‐TR mice were euthanized 1 week post‐injection. 0.5% biocytin internal solution was used to visualize cell morphology post hoc under a confocal microscope. Results: Pyramidal cells in the entorhinal cortex of APOE4‐TR mice (4 mice, n = 26 cells) exhibit significantly decreased spontaneous excitatory and inhibitory postsynaptic current frequencies, thereby contributing to an elevated excitatory‐inhibitory balance compared to APOE3‐TR mice (4 mice, n = 23 cells). Doxorubicin‐treated APOE3‐TR mice (4 mice, n = 33 cells) show a significant increase in spontaneous excitatory and inhibitory postsynaptic current amplitudes compared to controls (2 mice, n = 16 cells), while doxorubicin‐treated APOE4‐TR mice (5 mice, n = 20 cells) display no such synaptic changes compared to controls (4 mice, n = 19 cells). Conclusion: APOE4 has baseline effects on entorhinal cortex circuit inhibition and the lack of response to chemotherapy may reflect reduced resilience to stressors. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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