The study, conducted at The Picower Institute for Learning and Memory and Alana Down Syndrome Center at MIT, found that exposing mice genetically engineered to model Down syndrome to 40Hz light and sound stimulation improved cognition, circuit connectivity, and encouraged the growth of new neurons. This breakthrough has significant implications for individuals with Down syndrome, who often experience cognitive impairments.

The research team, led by Md Rezaul Islam and Brennan Jackson, used a technique called single cell RNA sequencing to examine gene expression in individual neurons. They found that many genes related to forming and organizing neural circuit connections were directly affected by the 40Hz stimulation. Furthermore, they observed an increase in synapses in a critical subregion of the hippocampus.

The study also showed that the 40Hz-stimulated mice exhibited more than unstimulated mice in neurogenesis, which is essential for generating new neurons. The researchers hypothesized that this increase in new neurons likely helps explain at least some of the increase in new synapses and improved short-term memory function.

This breakthrough has significant implications for individuals with Down syndrome, who often experience cognitive impairments. It also adds evidence that 40Hz-stimulated mice mount a homeostatic response to aberrations caused by disease pathology, be it neurodegeneration in Alzheimer’s or deficits of neurogenesis in Down syndrome.

However, the authors cautioned that the study had limits, including the use of an imperfect mouse model and male mice only. They also emphasized the need for further research, particularly examining changes in other cognitively critical brain regions such as the prefrontal cortex.

Breaking Down Barriers: Towards Gene-Targeting Drugs for Brain Diseases

The human brain is a complex and intricate organ that has long been a challenge to treat when it comes to diseases like Alzheimer’s, Parkinson’s, and brain cancers. One of the major obstacles in delivering therapeutic drugs to the brain is the blood-brain barrier (BBB), a protective layer that restricts the passage of molecules from the bloodstream into the brain.

To overcome this hurdle, researchers at Tokyo University of Science have been exploring new ways to deliver gene-targeting drugs, specifically antisense oligonucleotides (ASOs) and heteroduplex oligonucleotides (HDOs), directly to the brain. In a recent study published in the Journal of Controlled Release, the team led by Professor Makiya Nishikawa demonstrated that modifying HDOs with cholesterol molecules (Chol-HDOs) could improve their stability and specificity, allowing them to penetrate the cerebral cortex beyond the blood vessels.

The key to this success lies in how Chol-HDOs interact with proteins in the bloodstream. Unlike ASOs and HDOs, which bind electrostatically to serum proteins with low affinity and are taken up by cells, Chol-HDOs bind tightly to serum proteins, including lipoproteins, via hydrophobic interactions. This strong binding results in slow clearance from the bloodstream, allowing Chol-HDOs to remain in circulation for a longer period.

The researchers also showed that inhibiting scavenger receptors in cells reduces the uptake of both ASOs and Chol-HDOs in the liver and kidneys, shedding light on how these compounds are taken up by different organs. This finding has significant implications for the design of brain-targeting drugs based on Chol-HDOs.

With over 55 million people living with dementia worldwide and 300,000 cases of brain cancer reported annually, the potential therapeutic applications of modified HDOs are vast. The possibility of efficiently delivering ASOs and other nucleic acid-based drugs to the brain may lead to the development of treatments for brain diseases with significant unmet medical needs.

This study provides valuable insight into how brain-targeting drugs could be designed based on Chol-HDOs, paving the way for a new generation of compounds that effectively target brain diseases. As research continues, we can expect modified HDOs to offer hope to millions of patients and their families around the world.

Severe Heart Rhythm Disorders Persist After Valve Surgery in Some Patients

A recent study from Karolinska Institutet and Karolinska University Hospital in Sweden has found that some patients who undergo heart surgery for valve disorders may still be at risk of severe heart rhythm disorders, even after a successful operation. The study, published in the European Heart Journal, highlights the importance of closely monitoring these patients to prevent cardiac arrest.

The condition being studied is called mitral annular disjunction (MAD), which affects the mitral valve attachment and can lead to severe arrhythmias. Researchers at Karolinska Institutet investigated 599 patients with mitral valve prolapse who underwent heart surgery between 2010 and 2022, and found that 16% of them also had MAD.

The study showed that people with MAD were more likely to be female and younger than those without the condition, and had more extensive mitral valve disease. Although the surgery was successful in correcting MAD, these patients still had a higher risk of ventricular arrhythmias during five years of follow-up compared to patients without preoperative MAD.

“This is a concerning finding that highlights the need for closer monitoring of these patients after surgery,” said Bahira Shahim, associate professor at the Department of Medicine, Solna, Karolinska Institutet and cardiologist at Karolinska University Hospital. “Our results show that it’s essential to keep an eye on these patients even after a successful operation.”

The researchers are now investigating several hypotheses, including whether MAD causes permanent changes in the heart muscle over time or is a sign of underlying heart muscle disease. They are using MRI and analyzing tissue samples from the heart muscle to further study the condition.

The research was led by cardiologist and associate professor Bahira Shahim, along with Magnus Dalén and Klara Lodin. It was financed by ALF funds, the Swedish Heart-Lung Foundation, the Swedish Research Council, the Swedish Society for Medical Research, the Swedish Society of Medicine, and Karolinska Institutet.

In conclusion, this study highlights the importance of monitoring patients who have undergone valve surgery to prevent severe heart rhythm disorders, even after a successful operation. Further research is needed to fully understand the mechanisms behind MAD and how to best treat it.