The secret to our big brains might be in our gut

Brain tissue is among the most energetically costly in the body, and as a result, larger-brained mammals require more energy to support brain growth and maintenance. Exactly which biological changes allowed human ancestors to meet the very high needs for energy as they evolved larger brains has remained unclear. A new Northwestern University study points to the role of gut microbes, tiny living organisms in our digestive system that help break down food and produce energy.

In a controlled lab experiment, researchers implanted microbes from two large-brain primate species (human and squirrel monkey), and one small-brain primate species (macaque), into mice. Their findings showed the mice with microbes from large-brain primate species produced and used more energy, while those with microbes from the small-brain species stored more energy as fat. The data is the first to show gut microbes from different animal species shape variations in biology between animal species and supports the hypothesis that gut microbes might influence evolution by changing how an animal's body works. The study offers a new perspective on human evolution, particularly the evolution of our large brains. The findings will be published in the journal Microbial Genomics on Dec. 2. Prior studies have compared the influence of genes and the environment on primates with bigger and smallerbrains. However, there are very few studies comparing how different primates use energy. Even less information is available on how metabolism develops in different primate species. "We know the community of microbes living in the large intestine can produce compounds that affect aspects of human biology -- for example, causing changes to metabolism that can lead to insulin resistance and weight gain," said the study's first author Katherine Amato, associate professor of anthropology at Northwestern. "Variation in the gut microbiota is an unexplored mechanism in which primate metabolism could facilitate different brain-energetic requirements," Amato said. After introducing the gut microbes into microbe-free mice, the researchers measured changes in mouse physiology over time, glucose, liver function and other traits. They also measured differences in the types of microbes and the compounds they were producing in each group of mice. The researchers expected to find microbes from different primates would lead to differences in the biology of the mice inoculated with them. They also expected mice with human microbes to have the greatest difference in biology from mice with "While we did see that human-inoculated mice had some differences, the strongest pattern was the difference between large-brained primates (humans and squirrel monkeys) and smaller-brained primates (macaques)," Amato said. The mice given microbes from the humans and squirrel monkeys had similar biology, even though these two larger-brained primate species are not close evolutionary relatives of one another. This suggests something othermicrobes from the other two than shared ancestry -- likely their shared trait of large brains is driving the biological similarities seen in the mice inoculated with their microbes. "These findings suggest that when humans and squirrel monkeys both separately evolved larger brains, their microbial communities changed in similar ways to help provide the necessary energy," Amato said. In future studies, the researchers hope to run the experiment with microbes from additional primate species varying in brain size. They would also like to collect more information on the types of compounds the microbes are producing and gather additional data on the biological traits of the hosts such as immune function and behavior.species.including weight gain, fat percentage, fasting

Forgetfulness might depend on time of day

Pocket watch (stock image).

Can't remember something? Try waiting until later in the day. Researchers identified a gene in mice that seems to influence memory recall at different times of day and tracked how it causes mice to be more forgetful just before they normally wake up.

"We may have identified the first gene in mice specific to memory retrieval," said Professor Satoshi Kida from the University of Tokyo Department of Applied Biological Chemistry.

Every time you forget something, it could be because you didn't truly learn it -- like the name of the person you were just introduced to a minute ago; or it could be because you are not able to recall the information from where it is stored in your brain -- like the lyrics of your favorite song slipping your mind.

Many memory researchers study how new memories are made. The biology of forgetting is more complicated to study because of the difficulties of distinguishing between not knowing and not recalling.

"We designed a memory test that can differentiate between not learning versus knowing but not being able to remember," said Kida.

Researchers tested the memories of young adult male and female mice. In the "learning," or training, phase of the memory tests, researchers allowed mice to explore a new object for a few minutes.

Later, in the "recall" phase of the test, researchers observed how long the mice touched the object when it was reintroduced. Mice spend less time touching objects that they remember seeing previously. Researchers tested the mice's recall by reintroducing the same object at different times of day.

They did the same experiments with healthy mice and mice without BMAL1, a protein that regulates the expression of many other genes. BMAL1 normally fluctuates between low levels just before waking up and high levels before going to sleep.

Mice trained just before they normally woke up and tested just after they normally went to sleep did recognize the object.

Mice trained at the same time -- just before they normally woke up -- but tested 24 hours later did not recognize the object.

Healthy mice and mice without BMAL1 had the same pattern of results, but the mice without BMAL1 were even more forgetful just before they normally woke up. Researchers saw the same results when they tested mice on recognizing an object or recognizing another mouse.

Something about the time of day just before they normally wake up, when BMAL1 levels are normally low, causes mice to not recall something they definitely learned and know.

According to Kida, the memory research community has previously suspected that the body's internal, or circadian, clock that is responsible for regulating sleep-wake cycles also affects learning and memory formation.

"Now we have evidence that the circadian clocks are regulating memory recall," said Kida.

Researchers have traced the role of BMAL1 in memory retrieval to a specific area of the brain called the hippocampus. Additionally, researchers connected normal BMAL1 to activation of dopamine receptors and modification of other small signaling molecules in the brain.

"If we can identify ways to boost memory retrieval through this BMAL1 pathway, then we can think about applications to human diseases of memory deficit, like dementia and Alzheimer's disease," said Kida.

However, the purpose of having memory recall abilities that naturally fluctuate depending on the time of day remains a mystery.

"We really want to know what is the evolutionary benefit of having naturally impaired memory recall at certain times of day," said Kida.

About the research

Mice are naturally nocturnal. When measured in units of time using zeitgeber, the environmental cue of light turning on, mice are usually asleep from Zeitgeber Time 1 to 12 and awake from Zeitgeber Time 12 to 24. The term "just before normally waking up" refers to Zeitgeber Time 10, while the term "just after normally going to sleep" refers to Zeitgeber Time 4.

Collaborators at the Tokyo University of Agriculture and the University of Toronto also contributed to this research.

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Materials provided by University of Tokyo. Note: Content may be edited for style and length.