Dissertations and Theses

Date of Award

2025

Document Type

Thesis

Department

Biology

First Advisor

Karen Hubbard

Second Advisor

Jonathan levitt

Third Advisor

Mark Emerson

Keywords

HnrnpA1, Hippocampus, Doxorubicin, cyclophosphamide, Chemotherapy induced cognitive impairment, Neurons

Abstract

This study investigated the molecular mechanisms underlying chemotherapy-induced cognitive impairment (CICI) following doxorubicin and cyclophosphamide treatment in a rat model, revealing three significant alterations in hippocampal tissue: selective downregulation of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) (21% decrease, p=0.0298), compromised astrocytic network integrity evidenced by reduced GFAP-positive area in cornu ammonis 3 (CA3) (24%, pB=0.026) and dentate gyrus (DG) (19%, pB=0.027) regions, and elevated cellular senescence marker p19Arf specifically in DG (69%, pB=0.033) and CA3 (27%, pB=0.024). The inverse relationship between hnRNPA1 reduction and p19Arf elevation suggests a potential mechanistic link between RNA dysregulation and senescence induction, with pronounced vulnerability in regions critical for adult neurogenesis and memory processing, thereby providing molecular targets for developing neuroprotective strategies to mitigate cognitive impairment in cancer patients undergoing chemotherapy.

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