The Effect of High-Intensity Interval Training on Neuroplasticity-Related Proteins in the Cerebrum of Postnatally Growth-Restricted Mice

Introduction: Childhood growth-restriction can lead to lasting developmental changes, increasing susceptibility to chronic diseases and neurodegenerative conditions in adulthood. High-intensity interval training (HIIT) elevates brain-derived neurotrophic factor (Bdnf) levels more effectively than moderate intensity continuous exercise, supporting neuroplasticity. Building on these findings, this study aimed to determine whether HIIT could enhance neuroplasticity-related protein expression in the brains of PNGR mice. Methods: FVB mouse pups born to normal-protein and low-protein-fed dams were cross-fostered at postnatal day (PN) 1 to establish two groups: postnatally growth-restricted mice (PNGR) and control mice (CON). At PN 21, all pups were weaned onto a normal protein diet and assigned to either a high-intensity interval training group (TRD) or a sedentary group (SED). At PN 45, a maximal exercise performance test was conducted to determine HIIT intensities. Based on these results, mice performed treadmill HIIT 5 days per week for 4 weeks, with alternating intervals of 8 minutes at 85% and 2 minutes at 50% of maximal exercise capacity, totaling 60 minutes per session. At PN 73, all mice were euthanized, and cerebrum tissue was collected for western blot analysis of Bdnf, Tropomyosin receptor kinase B (TrkB), Growth-associated protein 43 (Gap-43), and synaptophysin protein expression. Results: Despite significant body mass reductions observed in both CON and PNGR groups following HIIT, neuroplasticity-related protein expression did not increase in PNGR mice. The PNGR group exhibited consistently lower TrkB and reduced Bdnf and Gap-43 levels compared to CON mice, indicating a limited neuroplastic response to exercise. Conclusions: Contrary to expectations, HIIT did not elevate neuroplasticity markers in PNGR mice, highlighting the lasting impact of early-life growth restriction on brain plasticity and suggesting the need for alternative interventions.