p53 Suppresses Autophagic Death in Hippocampal Stem Cells Under Chronic Stress in Mouse Model

The DGIST team exposed mice to repeated restraint stress and tracked LC3-p53 binding inside neural stem cells. Loss of p53 removed inhibition of the autophagy initiation complex, driving excessive self-digestion and cell loss. Low-dose RITA stabilized p53, blocked LC3 interaction, preserved stem-cell numbers, and prevented behavioral deficits. These outcomes were measured by immunohistochemistry, Morris water maze, and forced-swim tests.

Prior work established p53 as an apoptosis inducer in damaged cells, yet this study shows context-specific protection limited to stressed neural progenitors. The mechanism links glucocorticoid signaling to autophagy flux without invoking DNA damage pathways. Human relevance remains untested; no equivalent stem-cell assay or postmortem data were presented.

Next steps require conditional p53 models in aged mice, pharmacokinetic studies of RITA analogs in primates, and verification that p53 stabilization does not promote tumorigenesis in proliferative niches. A phase-0 microdose trial in stressed volunteers could assess hippocampal volume change by MRI.