Metabolism Controls the Timing of Human Brain Development and Maturation

ABSTRACT Among primates the human brain is the largest in size, exhibiting a higher neuronal density and connectivity. The prolonged expansion and subsequent connectome reorganization of the human brain have been suggested to promote higher cognitive and behavioral abilities. The notable variations in cognitive functions between human and nonhuman primates do not exclusively reside in neuronal abundance and connectivity but are also linked to a higher complexity in glial cells' morphology and functions at earlier time points, during embryonic brain development. Here we discuss two features of the human brain and their reciprocal connection. One feature is the high metabolic need of the developing and adult human brain. The other is its prolonged maturation, also known as neoteny. Even though the human brain occupies only a small percentage of the body mass, it is the highest consumer of glucose and oxygen. Among all brain cells, neurons have a great energy demand. Comparative studies suggest that increased glucose consumption and energy metabolism are positively correlated with higher cognitive abilities in humans. In line with the essential role of metabolism as a regulator of brain functions, recent breakthrough works have uncovered the correlation between metabolism and the timing of brain and neuron maturation during evolution. In this review, we specifically focus on the role of time in the evolution of the human brain and its synapses, focusing on the involvement of tissue, cellular, and subcellular metabolism.