A mouse model for autism and ADHD can mimic sex differences in sleep
or technically,
Hyperactivity and male-specific sleep deficits in the 16p11.2 deletion mouse model of autism.
[See Original Abstract on Pubmed]
Authors of the study: Angelakos CC, Watson AJ, O'Brien WT, Krainock KS, Nickl-Jockschat T, Abel T.
Falling asleep at night is something we look forward to at the end of the day, restoring our energy for the new day ahead. However, a good night's rest isn’t guaranteed for everyone as many people across the country have trouble sleeping. This is especially true for people diagnosed with autism spectrum disorders (ASD) and attention deficit-hyperactivity disorder (ADHD) who often have trouble falling asleep and staying asleep. Up to 80% of individuals diagnosed with ASD and 55% of children with ADHD suffer from sleep problems. Sleep disturbances can worsen other symptoms common in these disorders such as repetitive behaviors, attention, and communication. Christopher Angelakos, a graduate student in Dr. Ted Abel’s lab, wanted to understand why sleep disturbances are common in ASD and ADHD. In order to answer this question, Christopher turned to established models of ASD/ADHD. He reasoned that mice that have ASD/ADHD-like symptoms might also have sleep disturbances.
Patients with disorders like ASD/ADHD often have changes in the number of copies they have for a geneA unit of DNA that encodes a protein and tells a cell how to function. Typically, for each geneA unit of DNA that encodes a protein and tells a cell how to function there are two copies - one from each parent. Therefore, individuals with ASD/ADHD can have more copies, or fewer copies (also known as a deletion). One of these changes is a deletion in chromosomal region 16p11.2. People that have a deletion in this region are more likely to have ASD and ADHD. Previous research has shown that mice with a deletion in the 16p11.2 region show symptoms similar to ASD/ADHD like differences in brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. structure, cognitive ability, and communication. However, sleep problems remained largely unexplored, a problem that Christopher wanted to address.
Christopher observed that these animals were hyperactive, a behavior that is observed in individuals diagnosed with ADHD. He tracked all of the movements of the mice in their cages, observing an increase in activity in the 16p11.2 deletion mice throughout the day, and a robust increase during the dark (active) phase of their cycle. This led him to think that something may be altered in their circadian rhythms. To investigate this he monitored them for 24hrs and measured their sleep and activity to determine if it was normal.
He also examined their sleep cycles using polysomnography, which tracks brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. waves, eye movements, and limb movement during sleep. He wanted to know whether this was a problem of initiating sleep or maintaining sleep. He found that once the animals were asleep, they usually remained asleep for the same amount of time indicating that there was not a problem of staying asleep. On the other hand, once an animal was awake, it was usually awake for a longer period of time, indicating that it may have had trouble with initiating sleep. When Christopher further analyzed the data, he saw male mice with the 16p11.2 deletion spent a longer amount of time awake than regular mice. Coupled with his finding that these mice stay asleep as long as the regular mice, this suggests that they had a hard time falling asleep, rather than that they were waking up multiple times and having brief amounts of wakefulness. Interestingly, these disorders are more commonly found in males rather than females. Males are four times more likely to be diagnosed with ASD and three times more likely to be diagnosed with ADHD.
Issues with sleep in people that are diagnosed with autism or ADHD is a problem that needs to be addressed. Christopher asked whether we can use a mouse to model sleep problems in autism? He showed in his paper that the 16p11.2 deletion mouse can model sleep disturbances that are seen in humans. He is excited to see future work using this mouse model to uncover specific brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. circuits that may be involved and better treatment for sleep problems. Now that we have this experimental mode, we can determine if improving sleep quality will improve other psychiatric symptoms.
Patients with disorders like ASD/ADHD often have changes in the number of copies they have for a geneA unit of DNA that encodes a protein and tells a cell how to function. Typically, for each geneA unit of DNA that encodes a protein and tells a cell how to function there are two copies - one from each parent. Therefore, individuals with ASD/ADHD can have more copies, or fewer copies (also known as a deletion). One of these changes is a deletion in chromosomal region 16p11.2. People that have a deletion in this region are more likely to have ASD and ADHD. Previous research has shown that mice with a deletion in the 16p11.2 region show symptoms similar to ASD/ADHD like differences in brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. structure, cognitive ability, and communication. However, sleep problems remained largely unexplored, a problem that Christopher wanted to address.
Christopher observed that these animals were hyperactive, a behavior that is observed in individuals diagnosed with ADHD. He tracked all of the movements of the mice in their cages, observing an increase in activity in the 16p11.2 deletion mice throughout the day, and a robust increase during the dark (active) phase of their cycle. This led him to think that something may be altered in their circadian rhythms. To investigate this he monitored them for 24hrs and measured their sleep and activity to determine if it was normal.
He also examined their sleep cycles using polysomnography, which tracks brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. waves, eye movements, and limb movement during sleep. He wanted to know whether this was a problem of initiating sleep or maintaining sleep. He found that once the animals were asleep, they usually remained asleep for the same amount of time indicating that there was not a problem of staying asleep. On the other hand, once an animal was awake, it was usually awake for a longer period of time, indicating that it may have had trouble with initiating sleep. When Christopher further analyzed the data, he saw male mice with the 16p11.2 deletion spent a longer amount of time awake than regular mice. Coupled with his finding that these mice stay asleep as long as the regular mice, this suggests that they had a hard time falling asleep, rather than that they were waking up multiple times and having brief amounts of wakefulness. Interestingly, these disorders are more commonly found in males rather than females. Males are four times more likely to be diagnosed with ASD and three times more likely to be diagnosed with ADHD.
Issues with sleep in people that are diagnosed with autism or ADHD is a problem that needs to be addressed. Christopher asked whether we can use a mouse to model sleep problems in autism? He showed in his paper that the 16p11.2 deletion mouse can model sleep disturbances that are seen in humans. He is excited to see future work using this mouse model to uncover specific brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. circuits that may be involved and better treatment for sleep problems. Now that we have this experimental mode, we can determine if improving sleep quality will improve other psychiatric symptoms.
About the brief writer: Felicia Davatolhagh
Felicia is a PhD Candidate in Marc Fuccillo’s lab. She is a seventh year studying the impact of neuropsychiatric disease on synaptic connectivity and synaptic function.