This is a recurring column on early-stage research in animals or other laboratory models that has not entered the clinic yet but could have implications for future research and development of human medicines.

Linking skin scratching to food allergies

Researchers at Boston Children's Hospital have found a possible connection between scratching the skin and allergic reactions in the gut in a recent mouse study.

The study showed that scratching the skin results in an increased number of activated mast cells — immune cells that facilitate allergic responses — in the small intestine. The National Institute of Health's National Institute of Allergy and Infectious Diseases supported the research.

An established connection between the skin and the gut could help shed light on the link between food allergies and eczema, according to an NIH news release. Also known as atopic dermatitis, eczema is a strong risk factor for developing food allergies, but the connection between the two conditions are not well known. Eczema causes dry and itchy skin.

The research hypothesizes that scratching triggers the expansion of mast cells in the intestine.

The scientists conducted the study in mice by applying and removing small strips of tape on the skin of the rodents to simulate the act of scratching. The simulated scratching caused the production of a protein that triggers a chain reaction, reaching the gut and eventually activating the production of mast cells.

As the mast cells expanded, the intestinal lining became more permeable, which means allergens can pass more freely into the tissues. Mice that experienced the simulated scratching had more severe reactions to food allergens compared to those that did not.

The scientists also found more mast cells in intestinal biopsies from four children with eczema, compared to four children without the condition.

While the researchers think additional work is needed to find the relevance to humans, they suggest that efforts to limit itching can potentially lessen the severity of food allergy among patients with eczema.

Treating Down syndrome before birth

Scientists from Rutgers University-New Brunswick believe that targeting a certain gene before birth could eventually lead to a treatment for Down syndrome that reverses abnormal brain development and improves cognitive function.

Down syndrome is the most common chromosomal condition, affecting one in 700 babies in the U.S. Babies born with the condition have an extra copy of chromosome 21.

Researchers studied a gene called OLIG2, which is on chromosome 21. Stem cells from Down syndrome patients were used to develop two experimental models: a mouse brain model implanted with human cells and a living 3D organoid model of the brain. The models were used to investigate the condition in early brain development in the study, which was published in the journal Cell Stem Cell.

The scientists found that inhibitory neurons, which facilitate brain function, were overproduced in both brain models, while adult mice showed impaired memory. Inhibiting the OLIG2 gene led to improvements in the level of these neurons and reduced memory impairments.

"Our results suggest the OLIG2 gene is potentially an excellent prenatal therapeutic target to reverse abnormal embryonic brain development, rebalance the two types of neurons in the brain as well as improve postnatal cognitive function," said Peng Jiang, assistant professor in the Department of Cell Biology and Neuroscience at Rutgers University, New Brunswick.

Jiang also noted that the models used in the study could be applied to research in other neurodevelopmental disorders, such as autism spectrum disorder or Alzheimer's disease.

Ketamine helps keep depression-related behaviors away

Scientists noticed changes in the brains of mice treated with the club drug ketamine that suggest depression behaviors will not return post-treatment. The study was recently published in the journal Science.

Ketamine is known as a horse tranquilizer and club drug dubbed "Special K," but in recent years it has been examined as a promising therapy for treatment-resistant depression. The drug is a fast-acting therapy for depression that relieves symptoms of the condition in hours rather than weeks or months. Johnson & Johnson recently received U.S. Food and Drug Administration clearance for a nasal spray version called esketamine.

One of the challenges associated with the therapy is sustaining recovery after the initial treatment, according to Conor Liston of Weill Cornell Medicine, New York City, one of the authors of the Science study. The NIH's National Institute of Mental Health funded the study.

Researchers took images of dendritic spines — a nerve cell that receives communication input — in the mice's brains before and after they were introduced to stress. They found that the mice with symptoms of depression displayed either increased elimination or decreased production of these spines compared to mice that were not exposed to stress. Mice exposed to stress also had reduced functional connectivity and simultaneous activity in the neurons, which was associated with depression.

But in mice treated with ketamine, functional connectivity and activity in the nerve cells was rapidly restored, alleviating depression behaviors. After a single dose of ketamine, mice showed a reversal of the behaviors and an increase in dendritic spine formation after 24 hours, compared to the mice that did not receive the drug.

Formation of dendritic spines was found to play an important role in maintaining the remission of depression behaviors, the researchers said. Conversely, deleting newly formed dendritic spines led to a re-emergence of the behaviors.

"Our results suggest that interventions aimed at enhancing synapse formation and prolonging their survival could be useful for maintaining the antidepressant effects of ketamine in the days and weeks after treatment," Liston said.