Public defence: Linda Thøring Øverberg

High-intensity exercise makes the brain more plastic.

Exercise has a substantial effect on physical and mental health and boosts the brain’s ability to adapt to changes in the environment. This is called brain plasticity, and is important for normal brain functioning, learning, mood regulation, and a myriad of other processes in the brain. During high-intensity exercise, lactate is released from skeletal muscles. Lactate can activate a receptor for lactate called HCA1 (hereafter called “lactate receptor”) which among other places is located in the brain and seems to be important for the formation of new blood vessels in the brain. 

In this PhD-project we investigated if activation of the lactate receptor also increased the formation of new neurons (neurogenesis) in the two main neurogenic niches in the brain, the subventricular zone (SVZ) of the lateral ventricles which is important for odor/smells and olfactory memory, and the subgranular zone (SGZ) of the hippocampus which is important for learning and memory. 

We found that high-intensity exercise or lactate injection increased neurogenesis in the SVZ in response to activation of the lactate receptor in the normal (wildtype) mice, but not in mice lacking the lactate receptor (so called HCA1 KO mice). In the hippocampus, on the other hand, we found increased neurogenesis in both types of mice, whether they had or didn’t have the lactate receptor, in response to high-intensity exercise, but neurogenesis in this niche was unaffected by lactate treatment. Our findings show that neurogenesis is regulated differently in the two neurogenic niches, and that lactate is involved in the regulation of neurogenesis in the SVZ.

Exercise can prevent and treat depression. Therefore, we investigated whether high or moderate intensity exercise was more efficient in mood regulation, and whether activation of the lactate receptor was involved in this regulation. We found that activation of the lactate receptor contributes to the mood-enhancing effect of exercise in mice. All in all, the data generated in the present PhD-project suggest that activation of the lactate receptor contributes to increase neurogenesis in the SVZ as well as to the antidepressant effects of exercise. 

Finally, we examined the plasma levels of some key growth factors known to regulate neuroprotection and repair in patients with acute ischemic stroke. We analyzed blood samples from acute ischemic stroke patients and compared them with healthy age and gender matched controls. Excitingly, we found that some growth factor levels were significantly lower in stroke patients than in the controls. These findings indicate a reduced potential for plasticity and repair in stroke, where such mechanisms are necessary to prevent permanent brain damage. Further research is needed to determine whether these differences in growth factor levels, measured in the acute phase of stroke, can be used to predict post-stroke recovery and whether treatment with lactate or other agonists for the lactate receptor enhance post-stroke recovery.