High-Intensity Interval Exercise Regulates Neurotrophic Factors and Astrocyte Activity in the Hippocampus and Cerebral Cortex

Abstract

PURPOSE: Exercise training is now widely recognized as a complementary intervention that provides both therapeutic and preventive benefits for neurodegenerative diseases, given its strong association with brain health. Regulating the expression of neurotrophic factors can significantly enhance cognitive function and memory processes, particularly in conditions such as Alzheimer’s disease (AD). However, the effects of high-intensity interval aerobic exercise training (HIE) on brain-derived neurotrophic factors and astrocyte activation in the cortex (CTX) and hippocampus (HIP) remain obscure. Therefore, this study aimed to investigate HIE regulates the expression of neurotrophic factors and neuroinflammatory cytokines in the CTX and HIP. METHODS: 18-week-old female C57BL/6 mice were assigned to control (Cnt) and HIE group. After 12 week of HIE, the brains were harvested for immunoblotting, immunofluorescence, real-time PCR (qRT-PCR), and TUNEL assay. RESULTS: HIE increased the expression of glia-cell line-derived neurotrophic factor (GDNF) protein in the CTX but not in the HIP. Additionally, HIE induced a protective effect against neuroinflammation by significantly upregulating the A2-specific astrocytic transcripts. These findings suggest that HIE promotes neurotrophic and anti-inflammatory responses in both CTX and HIP. CONCLUSIONS: Our study results suggest that HIE exerts protective regulatory effects on neurotrophic factors, neuroinflammation, and A1/A2 type astrocytic reactivity in CTX and HIP of animal models. These findings suggested that HIE may have beneficial effects on brain health. However, as these results are derived from animal studies, further clinical research is needed to determine whether similar neuroprotective effects can be observed in humans. © 2025 Korean Society of Exercise Physiology.