Hurdle aerobic exercise increases angiogenesis and neuroplasticity in the hippocampus and improves the spatial memory ability of middle-aged mice

Irfannuddin Irfannuddin, Minarma Siagian, Sri Jusman, Jan Purba, Ermita Ilyas, Nurhadi Ibrahim

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Complex aerobic exercise is believed to induce positive effects on neuron structure and cognitive function. Long-term and continual cognitive stimulation increases neuroplasticity by stimulating the synthesis of neuronal growth proteins and the formation of new synapses. Exercise also increases the ability of neurons to survive and improves brain vascularization. Further investigations should be conducted to explore what types of aerobic exercise are beneficial for cognitive function. AIM: This study investigated the effects of hurdle aerobic exercise on developmentally regulated brain protein-A (Drebrin-A) as a neuroplasticity indicator, and on vascular endothelial growth factor (VEGF) as an angiogenesis marker in the hippocampus. METHODS: This study was an experimental study with post-test only control group design. Thirty-three adult mice were divided into control, hurdle aerobic runner (HAR), and plain aerobic runner (PAR) groups (n = 11 for each group). Fiberglass running wheels were originally designed and modified to assemble hurdles inside with adjustable speed. Speed adaptation was intended to achieve aerobic intensity. The experiment was performed 5 times a week for 8 weeks. The Morris water maze test (MWMT) was used to assess spatial memory ability. One day after the last running exercise and final MWMT, the mice were sacrificed and the right side of the hippocampus was obtained for Drebrin-A analysis by enzyme-linked immunosorbent assay (ELISA). The entire right side brain tissue after hippocampus was removed then used for the neuroglobin ELISA assay. To analyze VEGF expression and calculation of blood vessel, the left side of the brain was prepared for hematoxylin eosin and immunohistochemistry staining. To assess the effect of exercise on vascular widening, the analysis of the slides was performed by calculating the percentage of blood vessels with diameters more than 15 µm. One-way ANOVA and Fisher’s least significant difference test was used for statistical analysis. RESULTS: There was a significant difference in the levels of Drebrin-A between the HAR and PAR groups. Both exercise groups had higher levels of Drebrin-A than the control group. HAR and PAR groups exhibited significantly higher percentages of blood vessels expressing VEGF in hippocampus compared to control. HAR and PAR groups had the higher percentages of larger vessels compare to control. There was no significant difference of neuroglobin levels among the three groups. Both the HAR and PAR groups exhibited better spatial memory than the control group. CONCLUSION: Both aerobic exercises induced positive effects on brain angiogenesis, while the intensity of aerobic exercises did not result in high hypoxic stress in the brain.

Original languageEnglish
Pages (from-to)395-402
Number of pages8
JournalOpen Access Macedonian Journal of Medical Sciences
Issue numberA
Publication statusPublished - 2020


  • Drebrin-A
  • Hurdle aerobic exercise
  • Spatial memory, Neuroglobin
  • Vascular endothelial growth factor


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