Lifeboat Foundation: Safeguarding Humanity
Toggle light / dark theme

Blog

Category: genetics

Researchers trigger sleep’s restorative effect in parts of the awake brain

Scientists from the University of Wisconsin-Madison have successfully replicated some of the restorative effects of deep sleep in awake mice by artificially inducing slow-wave brain activity. Using optogenetics to control specific neurons, researchers triggered localized cortical activity that mimics the NREM sleep phase responsible for synaptic homeostasis and the reorganization of neural connections. This targeted stimulation significantly reduced signs of fatigue and improved memory retention and cognitive performance in the mice following prolonged wakefulness. While the researchers caution that this technique is not a substitute for natural sleep, the findings suggest that localized neural stimulation can effectively preserve brain function during extended periods of wakefulness. Future research aims to explore whether similar cognitive benefits can be achieved in humans through non-invasive methods, such as transcranial electrical stimulation.

NIH-funded study in animals offers new details about how the brain resets during sleep.

By inducing specific patterns of activity in small portions of the brain in awake mice, researchers supported by the National Institutes of Health (NIH) have triggered a recalibration of neural connections that normally only occurs during sleep. This new approach offset the effects of sleep deprivation in memory tasks and revealed features of sleep that are key to its restorative effect.

“What we’re essentially doing is forcing sleep in a local region of the brain. While that part is solidifying memories and restoring learning capacity, other parts stay aware/vigilant and connected to environment,” said corresponding author Chiara Cirelli, M.D., Ph.D., a professor of psychiatry at the University of Wisconsin-Madison. “Dolphins do something similar, sleeping with only one brain hemisphere at a time.”

Frontiers: Down syndrome (DS), also known as trisomy 21, is a genetic disorder caused by triplication of Chromosome 21

Gene triplication may compromise different body functions but invariably impairs intellectual abilities starting from infancy. Moreover, after the fourth decade of life people with DS are likely to develop Alzheimer’s disease. Neurogenesis impairment during fetal life stages and dendritic pathology emerging in early infancy are thought to be key determinants of alterations in brain functioning in DS. Although the progressive improvement in medical care has led to a notable increase in life expectancy for people with DS, there are currently no treatments for intellectual disability. Increasing evidence in mouse models of DS reveals that pharmacological interventions in the embryonic and neonatal periods may greatly benefit brain development and cognitive performance. The most striking results have been obtained with pharmacotherapies during embryonic life stages, indicating that it is possible to pharmacologically rescue the severe neurodevelopmental defects linked to the trisomic condition. These findings provide hope that similar benefits may be possible for people with DS. This review summarizes current knowledge regarding (i) the scope and timeline of neurogenesis (and dendritic) alterations in DS, in order to delineate suitable windows for treatment; (ii) the role of triplicated genes that are most likely to be the key determinants of these alterations, in order to highlight possible therapeutic targets; and (iii) prenatal and neonatal treatments that have proved to be effective in mouse models, in order to rationalize the choice of treatment for human application. Based on this body of evidence we will discuss prospects and challenges for fetal therapy in individuals with DS as a potential means of drastically counteracting the deleterious effects of gene triplication.

Down syndrome (DS) is a relatively high-incidence pathology (∼1 in every 800–1,000 live births; see Antonarakis et al., 2020; Hughes-McCormack et al., 2020) caused by triplication of Hsa21. Increased expression of Hsa21 genes (and genes on other chromosomes) impairs development and functions of various organs, including the brain (Bull, 2020). While some disorders may not be present in all individuals with DS, intellectual disability (ID) is the invariable hallmark of DS (Zigman, 2013; Ballard et al., 2016; Lott and Head, 2019). ID scores range from moderately (IQ of 50–70) to severely (IQ of 20–35; Bull, 2020) affected; even in its milder form, intellectual performance may compromise the ability to live independently. ID is already detectable in children with DS, especially regarding language, memory, and adaptive behavior, and is exacerbated with age (Godfrey and Lee, 2020).

Plasticity as a therapeutic target for improving cognition and behavior in Down syndrome

Early intervention and environmental optimization have been central to management of Down syndrome (DS) and much of current treatment is still focused in strategies that involve early education plans. This approach has provided significant improvements for Down syndrome but it is not providing a full success. The discovery of an increasing number of genes and molecular pathways linked to intellectual disability and involving a range of synaptic and plasticity-related mechanisms has open new treatment opportunities that focus on targeted treatments boosting neural plasticity. We here discuss some of these approaches, focusing on the effects of environmental enrichment and on the discovery of pharmacological therapies showing beneficial effects even in some clinical trials in adult individuals with Down syndrome. Targeting plasticity impairments in DS is thus a promising strategy to promote cellular mechanisms involved in learning and memory within key cognitive brain region and could lead to improved connectivity.

Keywords: EGCG; Environ-mimetic drugs; Environmental enrichments; Epigenetics; Neuronal plasticity.

© 2020 Elsevier B.V. All rights reserved.

Cholesterol-craving cancers need lipid enzymes to use metabolites for growth, study shows

While many American adults are trying to reduce cholesterol levels, certain cancerous tumors have a relentless appetite for the metabolite. Some tumor cells use as much cholesterol as they can access to accelerate their growth beyond the capabilities of normal cells.

Turning tumors’ cholesterol cravings into weakness Scientists at Sanford Burnham Prebys Medical Discovery Institute and their collaborators at the University of Illinois Chicago have published findings in Science Advances regarding a potential method for turning the tables on these tumors by subverting their cholesterol cravings. The researchers revealed new insights into enzymes that help move cholesterol around cells. Without the help of these enzymes, a cholesterol traffic jam occurs, blocking the cancer cell’s ability to fuel tumor growth.

Cancer cells with a mutation in the tumor-suppressing TP53 gene are known to produce extra cholesterol. This may make them more vulnerable to starvation if scientists can put a stop to the steady supply of the lipid.

Polyamine homeostasis in Caenorhabditis elegans relies primarily on transport

Chang and Jain develop a genetically encoded reporter to measure polyamines at single-cell resolution in C. elegans. By mapping polyamine control across tissues and development, they uncover organizing principles of in vivo polyamine regulation, including widespread reliance on transport and a central role for the intestine in coordinating systemic homeostasis.

Under pressure: peroxisomes in cancer therapy resistance

Therapy resistance is a major obstacle to durable clinical responses. While genetic alterations and signalling rewiring are primary drivers of resistance, metabolic adaptation, which is closely intertwined with these processes, enables tumour persistence under therapeutic pressure and directly contributes to resistance. Peroxisomes are metabolic organelles with a role in controlling lipid metabolism, together with redox signalling and homeostasis—processes that intersect with pathways governing cancer behaviour and therapy response. Indeed, peroxisomal functions are remodelled to support metabolic plasticity and redox buffering under therapeutic stress.

Antibody fragment prevents hemorrhages associated with new Alzheimer’s treatments

In 2025, the European Medicines Agency approved two antibodies for Alzheimer’s disease: lecanemab (LeqembiTM, from Biogen) and donanemab (Kisunla, from Eli Lilly and Co.), both based on immunotherapy (the use of molecules from the immune system to treat diseases). These antibodies, obtained in the laboratory, act against the Aβ peptide, a protein fragment that accumulates in the brains of patients with Alzheimer’s disease. Elimination of this protein by the immune system helps slow the characteristic cognitive decline of the disease.

These two antibodies are the first disease-modifying therapies for Alzheimer’s. They stop and, in some cases, even partially reverse this devastating condition. However, a frequent and characteristic side effect of these drugs is cerebral bleeding, detectable by magnetic resonance imaging. The brain does not have the molecules and cells that make up the systemic immune system, so the entry of antibodies into the brain is not desirable under healthy conditions, although it is necessary for these treatments to be effective.

The incidence of bleeding in clinical trials ranged from 10% to 27% of treated patients, with a particularly high incidence in individuals carrying a specific apolipoprotein allele: APOEε4. In Europe, these treatments can be administered only to people with one or no copy of the APOEε4 allele, a genetic variant associated with a higher risk of Alzheimer’s.

/* */