Oxidative Stress Mediated Glutamate Release and NMDA Receptor-Dependent Synaptic Remodeling in Radiation-Induced Cognitive Dysfunction

Author

• Thanh LamFollow

Author ORCID Identifier

0000-0003-1381-1892

Date of Graduation

8-2026

Document Type

Thesis (MS)

Program Affiliation

Neuroscience

Degree Name

Masters of Science (MS)

Advisor/Committee Chair

David R.Grosshans, M.D., Ph.D.

Committee Member

Joseph G.Duman, Ph.D

Committee Member

Michael Beierlein, Ph.D

Committee Member

Gabriel O. Sawakuchi, Ph.D

Committee Member

Steven H. Lin, M.D., Ph.D

Abstract

In children younger than 14 years old, the brain and other parts of the central nervous system are the most common sites for solid tumors. Radiotherapy is an effective treatment for central nervous system (CNS) tumors. However, it often causes a progressive decline in cognitive functions, which is especially devastating for pediatric patients. Although post-mitotic neurons are generally considered resistant to radiation-induced immediate cell death, ionizing radiation causes complex neurochemical and structural changes that damage synaptic integrity. In this study, we examined the molecular cascades following a 10 Gy radiation dose applied to mouse cortical neurons. We found that radiation-induced reactive oxygen species (ROS) and reactive nitrogen species (RNS) could trigger excessive extracellular glutamate release. This glutamate surge could initially be mediated by activation of N-methyl-D-aspartate receptors (NMDARs), followed by activation of AMPA receptors. Additionally, in vivo results show a significant memory decline in juvenile mice that received radiation treatment; pharmacological blockade of NMDARs by using memantine or ifenprodil pre-treatment could effectively prevent the radiation-induced memory deficit and preserve cognitive function.

Recommended Citation

Lam, Thanh, "Oxidative Stress Mediated Glutamate Release and NMDA Receptor-Dependent Synaptic Remodeling in Radiation-Induced Cognitive Dysfunction" (2026). Dissertations and Theses (Open Access). 1585.
https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1585

Keywords

radiation, memantine, NMDA, ROS, NO, glutamate, Puzzle Box, Y maze, neurotoxicity, Neuroprotective