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

Abstract

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 postnatally growth-restricted (PNGR) mice. Friend leukemia virus B mouse pups born to normal-protein and low-protein-fed dams were cross-fostered at postnatal day (PN) 1 to establish two groups: PNGR mice and control mice (CON). At PN 21, all pups were weaned onto a normal-protein diet and assigned to either a HIIT group (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 d·wk -1 for 4 wk, with alternating intervals of 8 min at 85% and 2 min at 50% of maximal exercise capacity, totaling 60 min per session. At PN 73, all mice were euthanized, and cerebrum tissue was collected for Western blot analysis of BDNF, tropomyosin receptor kinase B, growth-associated protein 43, and synaptophysin protein expression. Despite significant body mass reductions observed in both CON and PNGR groups after HIIT, neuroplasticity-related protein expression did not increase in PNGR mice. The PNGR group exhibited consistently lower tropomyosin receptor kinase B and reduced BDNF and growth-associated protein 43 levels compared with CON mice, indicating a limited neuroplastic response to exercise. 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.