Seeking the Gears of Our Inner Clock

Posted on December 29, 2015

Photo source: Flickr

Throughout the day, a clock ticks inside our bodies. It rouses us in the morning and makes us sleepy at night. It raises and lowers our body temperature at the right times, and regulates the production of insulin and other hormones. The body’s circadian clock even influences our thoughts and feelings. Psychologists have measured some of its effects on the brain by having people take cognitive tests at different times of day.

Another clue about the clock in our brains comes from people with conditions such as depression and bipolar disorder. People with these disorders often have trouble sleeping at night, or feel groggy during the day. Some people with dementia experience “sundowning,” becoming confused or aggressive at the end of the day.

“Sleep and activity cycles are a very big part of psychiatric illnesses,” said Huda Akil, a neuroscientist at the University of Michigan. Yet neuroscientists have struggled to understand exactly how the circadian clock affects our minds. After all, researchers can’t simply pop open a subject’s skull and monitor his brain cells over the course of each day.

A few years ago, Dr. Akil and her colleagues came up with an idea for the next best thing: The University of California stores brains donated to science. Some of their former owners died in the morning, some in the afternoon and others at night. Dr. Akil and her colleagues wondered if there were differences in the brains depending on the time of day the donors had died. They selected brains from 55 healthy people whose causes of death were sudden, such as in car crashes. From each brain, the researchers sliced tissue from regions important for learning, memory and emotions.

Because the brains had been quickly preserved, the scientists could still measure the activity of those genes at the time of death. Most of the genes they examined didn’t show any regular pattern of activity over the course of the day. But they found that more than 1,000 genes followed a daily cycle. People who died at the same time of day were making those genes at the same levels.

The patterns were so consistent that the genes could act as a timestamp. “We could ask, ‘What time did this person die?’” Dr. Akil said. “And we could pin it to within an hour of their actual recorded time of death.” She and her colleagues then ran the same analysis on the brains of 34 people who had had major depression before dying. Now they found that the time stamp was wildly off the mark. “It looked as if people were on Japan time or Germany time,” Dr. Akil said.

Dr. Akil and her colleagues inspired researchers at the University of Pittsburgh School of Medicine to attempt to replicate the study: More recently, Dr. McClung and her colleagues performed a bigger version of the study, examining 146 brains collected by the university’s donor program.

“Lo and behold, we got very nice rhythms,” Dr. McClung said. “It really seems like a snapshot of where the brain was at that moment of death.” Dr. McClung and her colleagues also did something no one had. They compared the patterns of gene expression in the brains of young and old people and found intriguing differences.

The scientists hoped to find clues to why people’s circadian cycles change as they age. “As people get older, their rhythms tend to deteriorate and shift forward,” Dr. McClung said. She found that some of the genes that were active in strong daily cycles in young people faded in people older than 60. It’s possible that some older adults stop producing proteins in their brains needed to maintain circadian rhythms.

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Category(s):Sleep Disorders

Source material from NY Times