A new study suggests that genetic changes unique to humans help protect our unusually large brains from damage, an “evolved neuroprotection” that may have enabled our brains to grow while maintaining healthy neurons over time.
These findings center on dopamine neurons, a critical link between brain areas governing emotion, movement, and higher cognition.
Although humans only have twice as many dopamine neurons as other primates, our prefrontal cortex (essential for reasoning and decision-making) is roughly 18 times larger than in macaque monkeys, and the striatum (involved in movement and emotions) about seven times larger.
With such disproportionate growth, each dopamine neuron faces greater metabolic and toxic stress.
Dopamine synthesis itself generates reactive oxygen species—highly destructive chemicals that can damage cells. Typically, neurons defend themselves by producing antioxidants and other protective molecules. Over time, however, these defenses can fail, contributing to neurodegenerative disorders such as Parkinson’s disease. Yet humans somehow maintain dopamine neurons in expanded brain regions without debilitating effects on average.
To explore why, researchers used “mini-brains” grown from stem cells of humans and non-human primates (chimpanzees, orangutans, and macaques). Growing multiple species’ cells side-by-side in the same environment allowed the team to parse which features were due to genetics rather than lab conditions. After roughly 100 days, the mini-brains produced dopamine neurons similar to those found in the striatum projecting toward the frontal cortex.
By analyzing over 105,000 cells, the team discovered that human dopamine neurons dial up the expression of genes that break down reactive oxygen species. When dosed with a pesticide known to increase these toxic molecules, human cells boosted production of BDNF (brain-derived neurotrophic factor), a well-known molecule that protects, nurtures, and rewires neurons. In contrast, chimpanzee cells in the same environment could not mount such a robust protective response.
These findings hint that evolution fine-tuned our dopamine neurons at the genetic level, equipping them with stronger defenses to manage the extra demands of a bigger, more complex brain. They may also inform treatments for diseases like schizophrenia, Parkinson’s disease, and addiction, all linked to dopamine neuron dysfunction. For instance, researchers could investigate whether mutations in the protective genes identified here increase vulnerability in certain individuals, opening the door to targeted interventions.
Ultimately, the study provides a deeper look at how human brains balance the energetic costs of a larger neural network while preserving key neurons over a lifetime. By illuminating the molecular underpinnings of dopamine neuron resilience, the work could spur new strategies for treating neurodegenerative disorders and inspire AI systems that learn in more brain-like ways.