summary: New research links childhood adversity to later attention deficits, sleep disorders, and certain dopamine imbalances in the brain. Scientists focused on critical periods of development and found that interruptions in care early in life affect men more than women.
In experiments, male mice had reduced attention and sleep patterns in adulthood, similar to the attention-deficit effects seen in humans. Remarkably, these defects were reversible with drugs targeting dopamine receptors.
Research suggests that early life stress and sleep deprivation affect the anterior cingulate cortex, affecting long-term concentration and emotional regulation.
Important facts:
- Early life adversity in mice caused persistent attention deficits in males but not females.
- Attention problems were associated with an imbalance of dopamine receptors in the anterior cingulate cortex.
- Treatments that modulate dopamine receptors restored attention even after the initial critical period.
sauce: Boston Children’s Hospital
A new study on the effects of childhood adversity has linked it to later life stress, poor sleep and poor attention span. It also reveals some of the underlying brain biology and potential therapeutic approaches, while also uncovering puzzling gender-specific effects.
Dr. Takao Hensch’s lab has long studied the window of time during development (commonly referred to as the critical period) during which the brain actively modifies its circuitry in response to experience.
In the cover story published in scientific translational medicineThe Hensch lab now shows that there is an early critical period when adversity, in this case parental neglect, impedes the development of attention.
“We have pinpointed the timing and mechanisms underlying attention problems in mice and linked them to human children,” said Boston Children’s Hospital FM Kirby Center for Neurobiology and Harvard University Center for Brain Science. says scientist Hensch.
Hensch and colleagues modeled early adversity by studying mice whose mothers had distracted and unstable care during the critical neonatal period. Male offspring, but not females, exhibited attention deficits in adulthood and performed poorly on attention-related visual tasks that required choices.
Apart from gender-specific problems, attention deficits appear to be caused by disrupted sleep patterns. In fact, sleep deprivation alone caused the same attention deficits in adult mice that had not experienced neglect.
Hensch believes there are similarities among humans. “We know that even just a few nights of sleep deprivation can lead to decreased alertness,” he says.
Adversity, stress, lack of sleep, decreased alertness
Interestingly, Hensch’s team identified a brain mechanism underlying attention deficits: differences in the balance of dopamine receptors in the anterior cingulate cortex (ACC), which regulate emotion and the control of thought and behavior.
Regardless of whether attention deficits result from parental neglect or directly from sleep deprivation in adulthood, one receptor, D2, is elevated while another, D4, is reduced. I did.
More surprisingly, this imbalance was reversible using drugs that either inhibit D2 receptors or stimulate D4. In both cases, treatment improved attention well after the critical period ended.
“We believe that dopamine signaling in the ACC is closely related to attention,” Hensch says.
Finally, the researchers found that in male mice, early adversity was associated with oxidative stress in the brain and increased levels of a peptide called orexin in the brain’s sleep center.
“Orexin is an arousal molecule and has been associated with sleep deprivation in men,” Hensch says.
Uncovering gender-specific effects
Why are the effects of early adversity and sleep deprivation unique to men? In a parallel human study conducted by the paper’s co-authors at the University of Pittsburgh and the University of Calgary, children (mostly boys) were aged between 3 and 5 years old. It has been confirmed that he has an attention deficit.
These findings are consistent with the known high prevalence of ADHD in boys and further indicate that gender differences emerge shortly after early childhood stress.
Hensch’s lab plans further studies to explore what makes females more resistant to adversity in both mice and humans.
“We think that women’s brains may protect themselves in unpredictable caregiving situations by integrating circuits more quickly,” Hensch says. “The downside is that by maturing too quickly, you may miss important later years.”
The researchers also hope to better understand the causes of dopamine receptor imbalance and which specific cell types in the ACC are affected. Ultimately, this research may lead to ways to help people with attention deficits.
The study was inspired by early human research on the effects of early adversity on cognition.
For decades in Romania, Dr. Charles Nelson, director of pediatric developmental medicine research at Boston Children’s Hospital, has shown that infants left in orphanages develop persistent cognitive and behavioral impairments, including attention deficits. I discovered that there is a trend. However, these effects were reduced when children were transferred to high-quality foster care before the age of 2 years.
“This study offers hope that brain circuits may be able to recover even after a critical period,” Hensch says. “There may be an opportunity for informed intervention.”
About this neurodevelopmental and neuroscience research news
author: Nancy Freisler
sauce: Boston Children’s Hospital
contact: Nancy Freisler – Boston Children’s Hospital
image: Image credited to Neuroscience News
Original research: Closed access.
“Expression of sleep-sensitive dopamine receptors in male mice underlies attention deficits after a critical period of early adversity” Written by Yuichi Makino et al. scientific translational medicine
abstract
Expression of sleep-sensitive dopamine receptors in male mice underlies attention deficits after a critical period of early adversity
Early life stress (ELS) causes cognitive impairment with unknown molecular and physiological causes.
We found that fragmented care by mouse mothers during the neonatal critical period from postnatal P2 to P9 increases the dopamine receptor D2R and suppresses the expression of D4R in the anterior cingulate cortex (ACC), especially in male offspring. I discovered that.
This was associated with decreased performance on a binary visual attention task and was acutely reversed in adulthood by local or systemic pharmacological rebalancing of D2R/D4R activity.
Furthermore, ELS male mice showed increased hypothalamic orexin and persistent sleep disturbance. Given that acute sleep deprivation in normally reared male mice mimicked the modulation of ACC dopamine receptor subtypes and disrupted attention in ELS mice, it is possible that sleep deprivation underlies the cognitive deficits in ELS mice. Highly sexual.
Similarly, sleep disturbances were shown to mediate attention deficits associated with early adversity in human children, as shown by path analysis of data collected with multiple questionnaires on a large pediatric cohort. .
Therefore, a deeper understanding of the gender-specific cognitive consequences of ELS may reveal therapeutic strategies to overcome ELS.
