**8. BHB can play a role in remyelination in the white matter of the brain**

In terms of functional recovery, both the neuronal structure and myelination are essential [3, 7]. As for the energy supply, the white matter axons of neurons are myelinated by oligodendrocytes. The astroglial end-feet are in direct contact with neurons only at Ranvier nodes, implying that neither glucose nor lactate can reach neurons easily. In fact, axonal metabolic demand is fulfilled by lactate supplied by oligodendrocytes. How lactate is generated by oligodendrocytes remains to be elucidated. Since astroglial end-feet are suitable for the uptake of glucose from microvessels, lactate generated in astroglia could be transported to oligodendrocytes; alternatively, a pathway involving the direct uptake of glucose by oligodendrocytes could be involved. Importantly, myelin damage (demyelination) can occur in various neurological disorders, while the remyelinating capacity can potentially restore damaged myelin (remyelination). Myelin cholesterol synthesis is essential for such a process, and BHB could be a possible substrate [62–65]. Moreover, BDNF reportedly facilitates myelination [66].

#### **9. Summary**

Brain function is dependent on glucose, which is supplied from outside the brain as food. The unavailability of glucose forces the brain to utilize ketone bodies, especially BHB. In addition to glucose and BHB, lactate is another possible energy source for the brain. Physical exercise enhances the production of both lactate and BHB. The former is generated in skeletal muscles, while the latter is generated in liver hepatocytes. Interestingly, astroglia can generate both lactate and BHB inside the brain upon neuronal excitation. Astroglia-derived lactate and BHB can serve as alternative energy substrates, since physical activities are initiated by neuronal excitation, which cause astroglia to generate lactate and BHB inside the brain. Irrespective of the origins of lactate and BHB, both can be transported into neurons and simulate BDNF production, facilitating neurotransmission and synaptic plasticity. Thus, physical activity helps the human brain to function in a healthy manner through a metabolic compartment composed of glial cells, skeletal muscles, and liver.

### **Acknowledgements**

The author thanks the Departments of Neurology and Physiology, Keio University School of Medicine, for their support. This work was supported in part by JSPS KAKENHI Grant Number 19 K08002 and 17 K09762.

*Lactate and Ketone Bodies Act as Energy Substrates as Well as Signal Molecules in the Brain DOI: http://dx.doi.org/10.5772/intechopen.97035*
