So human brains grew: our cells mastered the stress of size
So human brains grew: our cells mastered the stress of size
people developed disproportionately large brains compared to our primate relatives - but this neurological upgrade had its price. Scientists who examine this compromise have discovered unique genetic features that show how human brain cells deal with stress, to keep a large brain in function. This research could open up new approaches to better understand diseases such as Parkinson's and schizophrenia.
The study 1 concentrates on neurons that produce the neurotransmitter dopamine. This is crucial for movement, learning and emotional workmanship.
By comparing thousands of dopamine neurons bred in the laboratory, the researchers found that human dopamine neurons express more genes that promote the activity of harmful antioxidants than the neurons of other primates.
The results that are not yet peer-reviewed are a step towards "understanding the human brain evolution and all potentially positive and negative aspects that are connected with it," explains Andre Sousa, neuroscientist at the University of Wisconsin-Madison. "It is interesting and important to really find out what is specific to the human brain, with the potential to develop new therapies or even avoid illnesses in the future."
stressed neurons
How to lead to knee and back problems and led changes in the jaw structure and diet to dental problems, the quick expansion of the human brain has also created challenges for its cells for its cells, says the study gate Alex Pollen, neuroscientist at the University of California, San Francisco. "We have put up the hypothesis that a similar process took place and that these dopamine neurons could represent susceptible joints."
With an imaging process, pollen and his team showed that two dopamine -requiring regions of the brain are significantly larger in humans than with macaques. The prefrontal cortex is 18 times larger and the striatum is almost seven times larger.Nevertheless, people only have about twice as many dopamine neurons as their primate relatives, says Pollen. These neurons must therefore continue to be stretched and work harder - each forms more than two million synapses - in the larger, more complex human brain.
"The dopamine neurons are real athletes," says Nenad Sestan, development neuroscientist at Yale University in New Haven, Connecticut. "You are constantly activated."
to understand how human dopamine neurons may have adapted to meet the requirements of a large brain, breed pollen and his colleagues versions of these cells in the laboratory.
They combined stem cells-which can develop in many cell types-by eight people, seven chimpanzees, three macaques and an orangutan and breeded them to miniaturized, brain-like structures that are referred to as organoids. After 30 days, these structures began to produce dopamine and grinded a developing brain.
Then the team genetically seized the dopamine neurons to measure which genes were activated and how they were regulated.
In an analysis of human and chimpanzees, the researchers found that human neurons express higher amounts of genes that manage oxidative stress - a kind of cell damage caused by the energy -intensive process of dopamine production. These genes coded enzymes, the toxic molecules, so -called reactive oxygen species, dismantle and neutralize that can damage cells.
In order to examine whether human dopamine neurons may have developed unique stress reactions, the authors applied a pesticide that caused oxidative stress on the organoid. They found that neurons that had developed from human cells increased their production of a molecule called BDNF, which is reduced in people with neurodegenerative diseases such as Parkinson's. However, the same reaction was not observed in chimpanzees.
strengthening resilience
The understanding of these protective mechanisms could support the development of therapies that strengthen the cellular defenses of people who are at risk of developing Parkinson's. "Some of these protective mechanisms may not be available for everyone due to mutations," explains Sousa. "This creates additional vulnerability with these individuals."
"There are some potential target structures that could be very interesting to per-turbine and then transplant in [animal] models from Parkinson's to see whether they give the neurons more resilience," says Pollen.
The organoids examined in the study represent developing neurons that correspond to those who are present in an embryo and do not capture the full complexity of adult neurons. Future research has to investigate how such protective mechanisms remain in tires and aging neurons, says Sousa, since "degenerative diseases that affect these cells usually occur in a late age."
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Nolbrant, S. et al. Preprint at biorxiv: https://doi.org/10.1101/2024.14.623592