BDNF, endurance activity, and mechanisms underlying the evolution of hominin brains.

We contend that selection for endurance capabilities in a hot climate favored changes to muscle composition, mitochondrial dynamics and increased energy budget through pathways involving regulation of PGC-1α and MEF2 genes, both of which promote BDNF activity. In addition, the evolution of hairlessness and the skin's thermoregulatory response provide other molecular pathways that promote both BDNF activity and neurotransmitter synthesis. We discuss how these pathways contributed to the evolution of brain size and function in human evolution and propose avenues for future research. Our results support Raichlen and Polk's contention that selection for non-cognitive functions has direct mechanistic linkages to the evolution of brain size in hominins.