Medical Bulletin 12/ March/2024

Researchers develop blood-based markers to detect sleep deprivation

In a study published in the Journal Science Advances, researchers from Monash University, in Australia, and the University of Birmingham, in the UK have developed a blood test that can accurately detect when someone has not slept for 24 hours.

Sleep deprivation can adversely affect an individual's health by weakening the immune system, leading to increased susceptibility to illnesses. It also impairs cognitive function, memory, and decision-making abilities, which can affect performance at work and increase the risk of accidents.

Increased level of sleep deprivation increases the risk of serious injury or fatality in safety-critical situations. The biomarker developed used a combination of markers found in the blood of healthy volunteers. Together, these markers accurately predicted when the study volunteers had been awake for more than 24 hours under controlled laboratory conditions.

The biomarker accurately detects 24-hour wakefulness with 99.2% accuracy when compared to well-rested samples. Alone, it maintains high accuracy at 89.1%. This innovation holds potential for various safety-critical environments, mitigating risks of accidents due to sleep deprivation.

“This is a really exciting discovery for sleep scientists, and could be transformative to the future management of health and safety relating to insufficient sleep. While more work is required, this is a promising first step.” said Professor Clare Anderson Professor of Sleep and Circadian Science at the University of Birmingham.

The sleep deprivation biomarker can detect periods of wakefulness lasting 18 hours or more, although its primary focus is on identifying instances of 24 hours or longer without sleep. Developing a biomarker specifically for limited sleep during the previous night is a possibility, but further research is needed to integrate both the duration of wakefulness and the amount of sleep into accurate predictions.

References: KATHERINE JEPPE, SUZANNE FTOUNI, BRUNDA NIJAGAL, LEILAH K. GRANT, STEVEN W. LOCKLEY, SHANTHA M. W. RAJARATNAM, ANDREW J. K. PHILLIPS, MALCOLM J. MCCONVILLE, DEDREIA TULL, AND CLARE ANDERSON; Journal: Science Advances; DOI: 10.1126/sciadv.adj6834

Researchers demonstrate that viral infections present early risks to the heart

A new study led by James Smyth, associate professor at the Fralin Biomedical Research Institute, has revealed insights into fatal viral infections impacting the heart, suggesting that the virus initiates potentially hazardous conditions in the heart even before inflammation occurs.

Fatal viral infections can induce heart disease through various mechanisms. Firstly, some viruses can directly infect heart cells, leading to myocarditis and weakening of the heart muscle. Additionally, viral infections can provoke an exaggerated immune response, resulting in systemic inflammation and damage to blood vessels, thereby increasing the risk of atherosclerosis and cardiovascular events.

Viral infection accounts for the majority of myocarditis cases, leading to up to 42 percent of sudden cardiac deaths in young adults and due to this high occurrence of viral-related myocarditis resulting in sudden cardiac death, the insights are crucial.

"From a clinical perspective, our understanding of viral infection of the heart has focused on inflammation, causing problems with the rate or rhythm of the heartbeat. But we have found an acute stage when the virus first infects the heart and before the body's immune response causes inflammation. So even before the tissue is inflamed, the heart is being set up for arrhythmia." said Smyth.

Researchers studied adenovirus, a common cause of cardiac infection and myocarditis, using Mouse Adenovirus Type-3 to mimic human infection. Adenoviral infection disrupts gap junctions and ion channels in heart cells, affecting communication and electrical activity. This disturbance can lead to irregular heart rhythms (arrhythmias) and potential cardiac complications, particularly during active infections.

They discovered that the virus disrupts crucial components of the heart's communication and electrical systems early in the infection. This disruption can lead to irregular heart rhythms (arrhythmias) and potential cardiac complications, particularly during active infections. Researchers target these molecular changes to mitigate the risk of heart issues in individuals with viral illnesses.

"Individuals who have acute infections can look normal by MRI and echocardiography, but when we delved into the molecular level, we saw that something very dangerous could occur. In terms of diagnostics, we can now work and start looking ways to analyze blood for a biomarker of the more serious problem. People get cardiac infections all the time and they recover. But can we identify what's different about individuals that are at a higher risk to have the arrhythmia, possibly through a simple blood test in the doctor's office." concluded Smyth.

Reference: Rachel L. Padget, Michael J. Zeitz, Grace A. Blair, Xiaobo Wu, Michael D. North, Mira T. Tanenbaum, Kari E. Stanley, Chelsea M. Phillips, D. Ryan King, Samy Lamouille, Robert G. Gourdie, Gregory S. Hoeker, Sharon A. Swanger, Steven Poelzing, James W. Smyth. Journal: Circulation Research, 2024; DOI: 10.1161/CIRCRESAHA.122.322437

Research discovers growth cone aids neuronal migration and brain regeneration post-injury

A research group led by Kazunobu Sawamoto, Professor at Nagoya City University and National Institute for Physiological Sciences, along with Chikako Nakajima and Masato Sawada, have discovered that the PTPσ-expressing growth cone detects the extracellular matrix, facilitating neuronal migration in the injured brain and promoting functional recovery.

Postnatal mammalian brains contain neural stem cells that generate new neurons. These neurons migrate towards injured areas, and enhancing this migration aids functional recovery after brain injury. However, inhibitory effects on migration at injury sites need clarification to improve neuron recruitment and enhance recovery. Migrating neurons exhibit axonal growth cone-like structures at their tips, yet their role in migration remains partially understood.

The group examined the role of the growth cone-like structure in migrating mouse brain neurons. Using super-resolution microscopy, they studied its cytoskeletal dynamics and molecular features, revealing its similarity to axonal growth cones. Specifically, the growth cone responds to external signals via tyrosine phosphatase receptor type sigma (PTPσ), guiding migration directionality and initiating cell body movement. Chondroitin sulfate (CS) interaction with PTPσ causes growth cone collapse, inhibiting migration, while heparan sulfate (HS) interaction restores its extended morphology, enabling migration.

Further, they employed HS-containing gelatin-fiber non-woven fabric, a biomaterial offering structural scaffolding for cells like migrating neurons. Demonstrating that these fibers encouraged growth cone extension and neuronal migration in injured brains, they also found that implanting the HS-enriched gelatin fabric facilitated mature neuron regeneration and neurological function restoration. These findings imply that understanding the molecular mechanisms of growth cone interaction with the local extracellular environment may lead to innovative regeneration technologies promoting neuronal migration.

“To investigate whether the effect of HS in reversing the inhibitory effect of CS can promote neuronal migration in the injured brain, it was necessary to apply HS-containing biomaterial to the CS-rich injured brain,” said Sawamoto.

“Given that the growth cone of migrating neurons serves as a primer for neuronal migration under inhibitory extracellular conditions, it is necessary to further investigate whether the growth cone-mediated treatment to recruit new neurons from the endogenous source to the damaged sites is also applicable to aged brains,” said Nakajima.

Reference: Chikako Nakajima, Masato Sawada, Erika Umeda, Yuma Takagi, Norihiko Nakashima, Kazuya Kuboyama, Naoko Kaneko, Satoaki Yamamoto, Haruno Nakamura, Naoki Shimada, Koichiro Nakamura, Kumiko Matsuno, Shoji Uesugi, Nynke A. Vepřek, Florian Küllmer, Veselin Nasufović, Hironobu Uchiyama, Masaru Nakada, Yuji Otsuka, Yasuyuki Ito, Vicente Herranz-Pérez, José Manuel García-Verdugo, Nobuhiko Ohno, Hans-Dieter Arndt, …Kazunobu Sawamoto; Journal: Nature Communications; DOI: 10.1038/s41467-024-45825-8