Year: 2025
Type: conference-abstract
Abstract: BACKGROUND Radiation therapy is an integral part of treatment for patients with brain cancers. Radiation-induced brain injury (RIBI) occurs in over 50% of patients, causing cognitive and physical deficits such as memory loss and ataxia. There are no effective treatments for RIBI. The molecular mechanisms underlying RIBI are not well understood but are thought to involve radiation-induced DNA damage and oxidative stress that in turn damages brain cells. Apurinic/apyriminidinic endonuclease 2 (APE2) is a DNA damage repair protein induced by radiation. APE2 may have functions independent of DNA repair. HYPOTHESIS APE2 causes brain cell damage, causing volume loss and neurocognitive deficits. METHODS AND MATERIALS We created APE2 transgenic mice with Ape2LSL/+ in the Rosa26 locus and crossed them with CreERT2+/- mice. Mice were given TAM to induce Cre recombinase expression and subsequent expression of APE2. Mice underwent behavioral studies including novel object interaction and bar crawl. Immunostaining was performed in human and mouse brain. MRI was performed in Ape2LSL/+CreERT2+/- and CreERT2+/- control mice ex vivo. Mouse brain, cerebellum, and outer cortex were contoured and volumes were calculated . Mean and standard deviation were graphed using GraphPad Prism. Statistical significance was assessed by Mann-Whitney U test. RESULTS APE2 was overexpressed in neurons of RIBI patients and mice that received brain irradiation. APE2 was expressed in mitochondria, suggesting a role in regulating oxidative stress. APE2 transgenic mice exhibited ataxia and memory deficits and had smaller brains, cortexes, and cerebellums, than control mice. CONCLUSIONS APE2 transgenic mice exhibit signs of RIBI including ataxia and memory deficits, along with reduced cerebellum and cortex volumes, consistent with their neurologic deficits. These mice may serve as a model of RIBI. Further studies on molecular mechanisms of brain damage in APE2 mice may guide therapeutic strategies to prevent or mitigate the development of RIBI.
Source: Neuro-Oncology Advances
Authors: Daniel Lee, Jennifer Yu, Jianhong Lin, Jianjun Zhao
Institutions: Cleveland Clinic, University School
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,615
OpenAlex ID: W4413105774