Comparison of Different Exercise Modalities on Neuronal Plasticity and Spatial Memory

PURPOSE: The relationship between exercise and brain function has been studied extensively; however, whether different exercise modalities promote hippocampal neurogenesis and cognitive function through shared or distinct biological pathways remains unclear. This study examined the effects of endurance training (ET), resistance training (RT), and high-intensity interval training (HIIT) on hippocampal neurogenesis, spatial memory, and neurotrophic factors. METHODS: Forty 3-month-old male C57BL/6J mice were randomized to control (SED), ET, RT, or HIIT groups. Following the training intervention, adult hippocampal neurogenesis was assessed in the dentate gyrus using BrdU⁺/NeuN⁺ immunolabeling. Hippocampal measures of neurotrophic factors, including brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and fibronectin type III domain-containing protein (FNDC5), were quantified. Spatial memory was evaluated using the Barnes maze. RESULTS: All exercise modalities increased the number of BrdU⁺/NeuN⁺ cells compared with sedentary controls (RT, p<0.001; ET, p=0.001; HIIT, p=0.016). Each modality produced a distinct molecular profile. RT elicited the greatest increases in hippocampal BDNF compared to all groups (RT vs. ET, p=0.007; RT vs. HIIT, p<0.001; RT vs. SED, p<0.001) and increased IGF-1 levels (RT vs. SED, p=0.014). ET increased hippocampal FDNC5 (ET vs. SED, p=0.033), whereas HIIT did not alter measured neurotrophic or myokine levels. Only RT and ET improved spatial learning. CONCLUSIONS: Although all exercise modalities increased hippocampal neurogenesis, only those associated with elevations in neurotrophic factors demonstrated improvements in spatial learning. These findings suggest that different exercise modalities may promote hippocampal plasticity through distinct biological profiles and that increases in neurogenesis alone may not be sufficient to enhance cognitive function.