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Published on: October 18, 2011
Epigallocatechin-3-gallate Restores X-irradiation-Induced Impairments in Cognitive Function and Hippocampal
Kyung-Joo Seong1, Sang-Won Lee1, Jin Ho Lee2
1Dental Science Research Institute, Stem Cell Secretome Research Center, Hard-Tissue Biointerface Research Center, Department of Oral Physiology, School of Dentistry, Chonnam National University, Gwangju, 61186, Republic of Korea.
Abstract:
X-irradiation, commonly used to ablate tumor cells, disrupts hippocampal neurogenesis and neurobehavioral function. However, strategies to restore X-irradiation-induced impairments in hippocampal neurogenesis and cognitive function are not well established. Epigallocatechin-3-gallate (EGCG) is recognized as a neuroprotective agent in neurological disorders, but its effects on X-irradiation-induced impairments in hippocampal neurogenesis and memory function remain unclear. In this study, X-irradiation impaired adult hippocampal neurogenesis by suppressing neural stem cell (NSC) proliferation, survival, and differentiation, and it decreased cognitive function by reducing synapse number and expression. EGCG treatment restored hippocampal neurogenesis by reducing TLR4-NOX3/4-ROS levels and inhibiting neuroinflammation via the TLR4-NF-κB pathway, leading to the suppression of proinflammatory cytokines. Furthermore, TLR4 shRNA transfection in BV2 cells followed by X-irradiation significantly reduced the expression of NOX3 and NOX4 and decreased ROS production. Similarly, EGCG treatment in X-irradiated BV2 cells reduced TLR4, NOX3, and NOX4 expression, decreased cytosolic Nrf2 levels while upregulating nuclear Nrf2 expression, and enhanced HO-1 expression, leading to a reduction in ROS production. These findings suggest that EGCG may be a promising therapeutic strategy to restore X-irradiation-induced damage in the central nervous system, promoting hippocampal neurogenesis, memory function, and synapse development.
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