The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)
THE PROTECTIVE EFFECTS OF MEMANTINE ON THE MORPHOLOGY AND ACTIVITY OF IRRADIATED DENDRITIC SPINES
Author ORCID Identifier
Date of Graduation
Masters of Science (MS)
David R. Grosshans, M.D., Ph.D.
Wei Zhou, Ph.D.
Gabriel O. Sawakuchi, Ph.D.
Joseph G. Duman, Ph.D.
Cullen M. Taniguchi, MD., Ph.D.
Cobi J. Heijnen, Ph.D.
Abstract: The Protective Effects of Memantine on the Morphology And
Activity of Irradiated Dendritic Spines
Thanh T. Lam, M.S.
Advisory Professor: David R. Grosshans, M.D, Ph.D.
Although radiotherapy is an effective treatment for brain tumors, the adverse effects of such treatments may result in a decline in cognitive functioning. To prevent or reverse such radiation-induced cognitive dysfunctions, it is critical to understand the cellular and subcellular effects of radiation. In this study, both Thy-1 YFP mice and cultured cortical neurons were used to investigate changes in dendritic spines after cortical neurons were irradiated. The results indicated that irradiation has long-term and acute effects on the cortical dendritic spines. A decline in the density of the prefrontal cortical dendritic spines was observed one year after the irradiation of 2-week-old mice and pre-treatment of memantine, an NMDA receptor antagonist, prevented this decrease. Data also suggested that irradiation could have acute effects on the density and morphology of prefrontal cortical dendritic spines. Irradiation induced a decrease in spine density, decrease in proportion mushroom spines and increase in proportion stubby and branched spines. Time-lapse imaging was used to characterize the alterations of the dendritic spines of cultured cortical neuron upon radiation treatment, in real time, with or without memantine. The total activity was immediately increased in the neuron group irradiated without memantine pre-treatment, whereas the total activity of neuron group with both irradiation with memantine pre-treatment was not significantly altered. Hydrogen peroxide (H2O2) also induced acute effects on the dendritic spines of cultured cortical neurons. Both the spine density and dynamics were altered. Memantine could decrease the impact of H2O2 on dendritic spine only when neurons were treated with low concentration of H2O2. Together, these data help to understand more about the mechanisms of radiation effects on neurons and the protective effects of memantine. Ultimately, this may help lead to the development of better treatments for brain tumor patients.
Memantine, radiation, dendritic spine, brain tumor, time-lapse imaging, hydrogen peroxide