A combined team of psychiatrists and brain researchers from the University of Toronto and Québec Mental Health Institute in the Canada, working with a colleague from the National Research Council’s Institute of Biochemistry and Cell Biology, in Italy, has found that neurological problems associated with early life adversity (ELA) can be passed down at least three generations in mice.
In their study, reported in the journal Science Advances, the group conducted experiments with mice to learn more about ELA and a drug they tested to prevent the problem.
Prior research has shown that early life adversity can result in emotional and behavioral problems in both humans and mice. Prior research has also shown that such problems can be traced to changes in neurological functioning and can last a lifetime. In this new effort, the researchers took a closer look at ELA in mice to learn more about how it causes such problems and ways to fix the problems once found.
This involved subjecting mice pups to ELA—they took them away from their mothers and placed them with foster moms, and then repeatedly moved them to new foster moms every day for four days during the first week of life. The research team then tested the mice as they grew and reproduced.
They found heightened levels of the proteins encoded by the ASIC1, ASIC2 and ASIC3 genes in the periaqueductal gray matter and in the medulla oblongata—both of which are known to be involved in processing sensory pain. They also found that the mice were more sensitive to pain as adults and exhibited social and behavioral problems compared to control mice—and they tended to hyperventilate when exposed to CO2-enriched air.
As the mice grew older and were allowed to mate and produce offspring, the researchers tested the offspring, as well. They found heightened levels of the same proteins, which very strongly suggested that neurological problems associated with ELA can be passed down to offspring. The research team also found the same heightened levels of the same proteins in the third generation of mice.
The researchers also attempted to treat the malady by giving all three generations of mice the drug amiloride, which is known to reduce levels of proteins encoded by the ASIC1, ASIC2 and ASIC3 genes. They found that doing so not only reduced such levels but also reduced the physical symptoms the mice had been exhibiting.
Marco Battaglia et al, Enhanced harm detection following maternal separation: Transgenerational transmission and reversibility by inhaled amiloride, Science Advances (2023). DOI: 10.1126/sciadv.adi8750
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