The Journal of Physiology · Nov 23, 2024

High-intensity interval exercise is more efficient than medium intensity exercise at inducing neurogenesis

By Lambertus M, Geiseler S, Morland C

The neurogenic potential of the brain decreases during ageing, whereas the risk of neurodegenerative diseases and stroke rises. This creates a mismatch between the rate of neuron loss and the brain's capacity for replacement. Adult neurogenesis primarily occurs in the subgranular zone (SGZ) and the ventricular-subventricular zone (V-SVZ). Exercise enhances SGZ neurogenesis, and we previously showed that V-SVZ neurogenesis is induced by exercise via activation of the lactate receptor HCA₁. Here, we investigated how high-intensity interval training (HIIT) and medium-intensity interval training (MIIT) affect neurogenesis in these niches. Wild-type (WT) and HCA₁ knockout (KO) mice were randomized to sedentary, HIIT or MIIT (n = 5-8 per group) for 3 weeks. In the SGZ, HIIT increased the density of doublecortin (DCX)-positive cells in WT mice by 85% (5.77±1.76 vs. 3.12±1.54 cells/100 µm, P = 0.013) and KO mice (67% increase; 7.91±2.92 vs. 4.73±1.63 cells/100 µm, P = 0.004). MIIT did not alter the density of DCX-positive cells in either genotype. HIIT increased the density of Ki-67-positive cells only in KO mice (P = 0.038), whereas no differences in nestin-positive cells were observed. In the V-SVZ, HIIT increased the density of DCX-positive cells in WT mice by 155% (117.79±39.72 vs. 46.25±19.96 cells/100 µm, P < 0.001) and MIIT increased the density of DCX-positive cells by 80% (83.26±39.48 vs. 46.25±19.96 cells/100µm, P = 0.027). No exercise-induced changes were observed in KO mice. Similar patterns were noted for Ki-67 positive and DCX/Ki-67 double-positive cells in the V-SVZ. These findings suggest that HIIT enhances neurogenesis more robustly than MIIT in both niches, with HCA₁ playing a crucial role in V-SVZ neurogenesis. KEY POINTS: The neurogenic potential of the brain decreases with age, whereas the risk of neurodegenerative diseases and stroke increases, highlighting a mismatch between neuronal loss and replacement capacity. Exercise enhances neurogenesis in both the subgranular zone and the ventricular-subventricular zone. High-intensity interval exercise is more effective than medium-intensity interval exercise at promoting neurogenesis in both the subgranular zone and the ventricular-subventricular zone of wild-type mice. The enhancement of neurogenesis in the ventricular-subventricular zone is dependent on the activation of the HCA₁ receptor, as evidenced by the ability of medium- and high-intensity interval exercise to induce neurogenesis in wild-type mice and the lack of this effect in HCA₁ knockout mice. By contrast, neurogenesis in the subgranular zone is independent on the activation of the HCA₁ receptor, highlighting that neurogenesis in the two major neurogenic niches are regulated differently.

doi.org/10.1113/jp287328 Open access PubMed 39580614 Interventions