RNA gene expression and cognitive reserve as determinants of post-ischaemic stroke cognitive recovery

 

Biomarkers do nothing for recovery unless you are mapping EXACT RECOVERY PROTOCOLS to them! You're all fired for useless shit!

RNA gene expression and cognitive reserve as determinants of post-ischaemic stroke cognitive recovery

Abstract

Cognitive impairment is a common yet under-recognised complication of ischaemic stroke (IS), with long-term effects on patient quality of life and rehabilitation outcomes. Identifying early biomarkers and protective factors such as cognitive reserve (CR) is essential for improving prognosis and guiding targeted interventions. This study aimed to determine the following: (i) RNA gene expression profiling during acute stroke and (ii) the associations between target genes as well as clinical factors and cognitive impairment during an acute event and at the 3-month follow-up. A three-month prospective cohort study involving 24 adults with mild to moderate IS and 24 age- and sex-matched controls admitted to Hospital Canselor Tuanku Muhriz, Malaysia, was conducted. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) within 48 h of stroke and at 3 months. Peripheral blood samples were collected for RNA extraction, and gene expression was analysed using RT² Profiler PCR arrays. Cognitive reserve was measured using the Cognitive Reserve Index Questionnaire (CRI-q). Statistical analyses included chi-square and independent t tests. At baseline, 83.3% of IS patients exhibited cognitive impairment (mean age 64.6 ± 10.5 years). Increased age (p = 0.006), low education level (p = 0.010), diabetes mellitus (p = 0.010), CRI-Education (p = 0.010) and CRI-Working Activity (p = 0.009) were significantly associated with baseline cognitive impairment. These clinical and CR factors survived False Discovery Rate (FDR) correction at the baseline stage (p < 0.05). However, at the 3-month follow-up, no clinical or CR factors remained statistically significant after FDR correction. Regarding gene expression, while MAPK1 (p = 0.029) and CAPZB (p = 0.042) were nominally upregulated in patients, and RCOR1 (p = 0.043) showed a nominal association with baseline impairment, no genetic markers survived FDR correction at either time point. Age, diabetes, and cognitive reserve are robust determinants of cognitive status during the acute phase of ischaemic stroke. The loss of significance at 3 months suggests these factors are primary drivers of initial functional buffering rather than long-term recovery trajectories in this cohort. CR should be utilised as a prognostic stratification tool during admission to identify high-risk patients rather than as a direct target for acute intervention. Future large-scale studies are required to validate whether the observed nominal gene expression trends can serve as reliable biomarkers for long-term recovery.

Neurons Use RNA “Tentacles” to Survive Starvation

 Will your competent? doctor and hospital ensure further research occurs that identifies a way to use this to save neurons during and immediately post stroke?

Do you prefer your doctor, hospital and board of director's incompetence NOT KNOWING? OR NOT DOING? Your choice; let them be incompetent or demand action!

Neurons Use RNA “Tentacles” to Survive Starvation

ummary: Neurons are high-energy cells that must find ways to survive when nutrients are scarce. New research has discovered a fascinating survival mechanism: neurons pair up their protein factories (ribosomes) into inactive “disomes” to save energy.

Unlike bacteria, which use proteins to link ribosomes, animal cells use long, flexible RNA “tentacles” called expansion segments. These segments form a “kissing loop” that locks ribosomes together during stress, protecting these expensive molecular machines until favorable conditions return.

Key Facts

• The Energy-Saving Disome: When stressed (by cold or lack of food), animal cells assemble inactive ribosomes into pairs called disomes to halt costly protein production.
• RNA Tentacles: The connection is made by a specific ribosomal RNA segment called “31b,” an expansion segment that acts like a tentacle protruding from the ribosome.
• The “Kissing Loop”: These RNA tentacles bind to each other through complementary sequences, forming a precise, reversible lock.
• Cryo-ET Visualization: Researchers used cryogenic electron tomography to see these ribosome pairs directly inside intact, frozen cells for the first time.
• Evolutionary Clue: Expansion segments have grown larger over the course of evolution; this study reveals they play a key role in how complex organisms manage cellular stress.

Source: Max Planck Society

Ribosomes are large molecular machines made of protein and RNA that build all proteins in the cell.

Because protein production is extremely energy-intensive, cells rapidly reduce protein synthesis when stressed. It has long been known that bacterial cells pair their inactive ribosomes into so-called “hibernating disomes” however, such structures had not previously been identified in animal cells.

During periods of extreme stress, animal cells use ribosomal RNA expansion segments to form inactive pairs, protecting their protein-making machinery while conserving energy. Credit: Neuroscience

An unexpected role for ribosomal RNA during cellular stress

Using advanced imaging techniques, Erin Schuman and her team at the Department of Synaptic Plasticity at the Max Planck Institute for Brain Research in Frankfurt discovered that stressed animal cells – including neurons – assemble inactive ribosomes into tightly linked pairs, known as disomes. These ribosome pairs are not accidental collisions or artifacts, but a regulated and reversible response to stress.

The new study was published today in Science.

“Surprisingly, the two ribosomes are not held together by proteins, as is common in bacteria. Instead, the connection is made by a specific piece of ribosomal RNA called an expansion segment”, explains one of the lead authors, postdoctoral researcher, Andre Schwarz.

Expansion segments are long, flexible RNA “tentacles” that protrude from ribosomes and have grown larger over the course of evolution. Although they are a prominent feature of animal ribosomes, their functions only just started to emerge. This study now shows that one particular expansion segment, called “31b”, is both necessary and sufficient to link ribosomes together during stress

. At the molecular level, the expansion segment forms a precise RNA-RNA interaction – a so-called “kissing loop” – in which identical RNA loops bind each other through complementary sequences. Disrupting this interaction prevents disome formation, stunts cellular growth and makes cells more sensitive to stress.

Seeing ribosomes inside cells

A key strength of the study was the ability to visualize ribosomes directly inside intact cells using cryogenic electron tomography (Cryo-ET). Cryo-ET is a powerful 3D imaging technique that uses an electron microscope to see inside frozen biological samples (cells, organelles, molecules) with very high resolution. This approach allowed the team to visualize ribosomes in their native environment and resolve how they re-organize during stress.

The study combined an unusually broad range of techniques, including cell biology, biochemistry, yeast and mammalian cell genetic engineering, and high-resolution structural imaging.

“One major challenge was manipulating ribosomal RNA, which is encoded by hundreds to thousands of nearly identical gene copies in animal genomes. We overcame this hurdle by engineering hybrid ribosomes in yeast and by introducing small RNA molecules that specifically disrupted ribosome pairing in animal cells”, says Mara Mueller, graduate student in the Schuman Lab and co-first author of the study.

A new view of translation control

„Our findings uncover a previously unknown mechanism by which animal cells regulate protein synthesis during stress – one that relies on RNA structure. The study reveals a new function for ribosomal RNA expansion segments which have been rather mysterious”, says Erin Schuman.

By temporarily storing ribosomes in inactive pairs, cells protect these costly machines and enable rapid recovery once favorable conditions return. The discovery opens new avenues for understanding how cells adapt to stress and how ribosome organization contributes to health and disease.

Key Questions Answered:

Q: Why would a cell want to stop making proteins?

A: Making proteins is the most energy-intensive thing a cell does. In a crisis (like starvation), a cell has to cut its “spending.” By pairing up ribosomes and putting them in “hibernation,” the cell saves massive amounts of energy to stay alive.

Q: What happens if this pairing process is broken?

A: The study found that if the RNA “kissing loop” is disrupted, cells cannot properly enter hibernation mode. This stunts growth and makes the cells much more likely to die when conditions get tough.

Q: How did they see something this small?

A: They used Cryo-ET, which involves “plunge-freezing” cells so quickly that the water doesn’t form ice crystals. This preserves the cell in its natural state, allowing an electron microscope to take high-resolution 3D pictures of the molecules inside.

Editorial Notes:

• This article was edited by a Neuroscience News editor.
• Journal paper reviewed in full.
• Additional context added by our staff.

About this genetics and neuroscience research news

Author: Irina Epstein
Source: Max Planck Institute
Contact: Irina Epstein – Max Planck Institute
Image: The image is credited to Neuroscience News

Original Research: Closed access.
“rRNA expansion segments mediate the oligomerization of inactive animal ribosomes” by Andre Schwarz, Mara Mueller, Helene Will, Lea Dietrich, Stefano L. Giandomenico, Georgi Tushev, Ina Bartnik, Iskander Khusainov, Claudia M. Fusco, Erin M. Schuman. Science
DOI:10.1126/science.adr4287

Dietary RNA Molecules May Hold the Key to Slowing Cellular Aging

 Your competent? doctor is all over healthspan and will guarantee that this research gets done in humans. Oh, you don't trust your doctor to accomplish either point! I wouldn't either. 

healthspan (6 posts to December 2024)

Dietary RNA Molecules May Hold the Key to Slowing Cellular Aging

Summary: Living longer doesn’t always mean living healthier, and researchers are exploring how diet can extend healthspan. A study in worms shows that specific dietary RNA molecules protect cells from harmful protein build-up, a major driver of aging and age-related disease.

These RNAs activate stress responses and autophagy, enhancing resilience and slowing cellular aging across the body. While still early-stage research, the findings suggest diet could play a powerful role in promoting healthier aging in humans too.

Key Facts

• Dietary RNA Benefits: Food-based RNAs reduce harmful protein aggregates.
• Protective Mechanism: They trigger autophagy and stress resilience pathways.
• Whole-Body Impact: Worms lived healthier and more active lives with balanced diets.

Source: University of Basel

People are living longer than ever, but a long life doesn’t necessarily mean a healthy one.

For many, the question isn’t so much “How old do I want to get?” but rather “How do I want to get old?”. While lifespan refers to the years we live from birth to death, “healthspan” describes the number of years we spend in good health.

Healthy aging is also a question of diet. It’s long been known that not just the quantity, but also the individual nutrients impact how we age. Using the tiny worm Caenorhabditis elegans, Spang’s team has now demonstrated that certain RNA molecules in food have a positive effect on the worm’s fitness in old age.

“These molecules prevent the formation of harmful protein aggregates that are typically linked with aging and disease,” says Spang.

The results of their study have been published in “Nature Communications”.

How diet shapes aging

With age, the body becomes less efficient at removing altered and damaged proteins. These can accumulate and form harmful protein aggregates in cells. Such protein aggregates are considered drivers of aging and are associated with multiple age-related diseases including muscular and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease.

The researchers have discovered that a balanced diet promotes healthspan and specific components in the nematode’s diet exert a protective effect. The worms feed mainly on bacteria that contain double-stranded RNA molecules.

“These dietary RNAs are absorbed in the gut and activate quality-control mechanisms to protect from cellular stress,” explains Emmanouil Kyriakakis, the study’s first author.”

This low-level stress essentially trains the body to cope with protein damage more effectively.”

Diet-dependent mechanisms slow cellular aging

Diet activates autophagy—a cellular “clean-up” process that degrades and recycles damaged proteins. This mechanism reduces harmful protein aggregation and thus slows down cell aging.

“We were surprised to find that the gut communicates with other organs,” says Kyriakakis. “We observed protective effects not only locally, but also in muscles and throughout the whole organism.”

Healthier aging — even in worms
Overall, the worms exposed to a balanced diet were more active and healthier in old age.  “The dietary-RNA species elicit a systemic stress response that protects the worms from protein aggregation during aging,” says Kyriakakis. “thereby extending their healthspan.”

The findings confirm that diet strongly influences health in old age. “Specific food components can stimulate the body’s own protective mechanisms,” adds Spang.

“So, a little stress can be good for you.” Whether individual nutrients can also spark beneficial effects in humans – and potentially help prevent age-related diseases – remains to be investigated. But it’s certainly conceivable. What is clear already: What we eat can shape the way we age.

Key Questions Answered:

Q: What is healthspan, and how does it differ from lifespan?

A: Healthspan refers to the number of years spent in good health, whereas lifespan is simply the total years lived.

Q: How does diet affect aging at the cellular level?

A: Certain dietary RNA molecules help prevent harmful protein aggregates and activate cellular clean-up processes like autophagy.

Q: What did the study on worms reveal about dietary RNA?

A: Worms fed bacterial RNAs showed reduced protein damage, stronger stress defenses, and healthier aging overall.

About this diet, genetics, and aging research news

Author: Angelika Jacobs
Source: University of Basel
Contact: Angelika Jacobs – University of Basel
Image: The image is credited to Neuroscience News

Noncoding RNAs and Stroke

No clue. Ask your doctor.
http://journals.sagepub.com/doi/abs/10.1177/1073858418769556

Xuejing Zhang, Milton H. Hamblin, Ke-Jie Yin

First Published April 11, 2018 Research Article

Download PDF	Article information

Abstract

Over many years, extensive efforts have focused on the development and improvement of diagnostic and therapeutic strategies to reduce stroke-associated neurovascular damage, such as blood-brain barrier dysfunction, brain edema, parenchymal inflammation, and neural cell death. However, the only clinically applied pharmacological therapy to date for the treatment of acute ischemic stroke is thrombolysis. Because of the short therapeutic window of current thrombolytic therapy and the activation of various pathophysiological signaling cascades triggered after ischemic stroke, the development of new therapies is urgently required. Noncoding RNAs (ncRNAs) are defined as untranslated regulatory RNA molecules. Although ncRNAs with biological roles have been known for almost 60 years, they have within the past decade emerged as key mediators of posttranscriptional gene expression/function in pathological aspects of ischemic stroke. With properties of relative stability, specificity, and reproducibility, ncRNAs are considered to be promising as biomarkers and better candidates than proteins and genes for early recognition of the onset of disease. In this update, we summarized the current knowledge for three groups of ncRNAs in stroke, focusing on the role of long noncoding RNAs and circular RNAs as biomarkers for stroke and as targets for regulating large sets of genes in related pathways after ischemic stroke.

Team finds key to making neurons from stem cells - RNA molecule called Pnky

Whom is updating the stroke strategy to put this into the right place and schedule followup research?
http://m.medicalxpress.com/news/2015-03-team-key-neurons-stem-cells.html?
A research team at UC San Francisco has discovered an RNA molecule called Pnky that can be manipulated to increase the production of neurons from neural stem cells.
The research, led by neurosurgeon Daniel A. Lim, MD, PhD, and published on March 19, 2015 in Cell Stem Cell, has possible applications in regenerative medicine, including treatments of such disorders as Alzheimer's disease, Parkinson's disease and traumatic brain injury, and in cancer treatment.

Pnky is one of a number of newly discovered long noncoding RNAs (lncRNAs), which are stretches of 200 or more nucleotides in the human genome that do not code for proteins, yet seem to have a biological function.

The name, pronounced "Pinky," was inspired by the popular American cartoon series Pinky and the Brain. "Pnky is encoded near a gene called 'Brain,' so it sort of suggested itself to the students in my laboratory," said Lim. Pnky also appears only to be found in the brain, he noted.

Co-first authors Alex Ramos, PhD, and Rebecca Andersen, who are students in Lim's laboratory, first studied Pnky in neural stem cells found in mouse brains, and also identified the molecule in neural stem cells of the developing human brain. They found that when Pnky was removed from stem cells in a process called knockdown, neuron production increased three to four times.

"It is remarkable that when you take Pnky away, the stem cells produce many more neurons," said Lim, an assistant professor of neurological surgery and director of restorative surgery at UCSF. "These findings suggest that Pnky, and perhaps lncRNAs in general, could eventually have important applications in regenerative medicine and cancer treatment."

Lim observed that Pnky has an intriguing possible connection with brain tumors.

Using an analytical technique called mass spectrometry, Ramos found that Pnky binds the protein PTBP1, which is also found in brain tumors and is known to be a driver of brain tumor growth. In neural stem cells, Pnky and PTBP1 appear to function together to suppress the production of neurons. "Take away one or the other and the stem cells differentiate, making more neurons," said Lim. "It is also possible that Pnky can regulate brain tumor growth, which means we may have identified a target for the treatment of brain tumors."

Lim said that the larger significance of the research is that it adds to a growing store of knowledge about lncRNAs, previously unknown sections of the genome that some biologists have referred to as the "dark matter" of the human genome.

"Recently, over fifty thousand human lncRNAs have been discovered. Thus, there may be more human lncRNAs than there are genes that code for proteins," said Lim. "It is possible that not all lncRNAs have important biological functions, but we are making a start toward learning which ones do, and if so, how they function. It's a new world of experimental biology, and the students in my lab are right there on the frontier."

Lim had particular praise for Ramos, an MD-PhD student in the UCSF Medical Scientist Training Program, and Andersen, who has a fellowship from the prestigious National Science Foundation (NSF) Graduate Research Fellowship Program. "They have been a great collaborative team and an inspiration to others in my lab," said Lim. "I think they represent the pioneering, investigative spirit of the UCSF student body."
Provided by University of California, San Francisco

How Your Brain Circuits Become Miswired

Our researchers should be able to follow this research to figure out how to guide axons around dead areas to reconnect up the various parts of the brain. It might be challenging to do but no more challenging than recovering from a stroke. And they have full use of their brains. No excuses allowed.
http://psychcentral.com/news/2013/06/08/how-your-brain-circuits-become-miswired/55790.html
How do the faulty brain circuits involved in mental disorders such as autism or retardation develop? Researchers at Weill Cornell Medical College have helped light the way to an answer with the discovery of a mechanism that guides the wiring of neural circuits in a developing brain.
The researchers discovered that faulty wiring occurs when RNA molecules embedded in a growing axon are not degraded after they give instructions that help steer the nerve cell.
For example, the signal that tells the axon to turn — which should disappear after the turn is made — remains active, interfering with new signals meant to guide the axon in other directions.
“Understanding the basis of brain miswiring can help scientists come up with new therapies and strategies to correct the problem,” said the study’s senior author, Samie Jaffrey, M.D., Ph.D.
“The brain is quite plastic and changeable in the very young, and if we know why circuits are miswired, it may be possible to correct those pathways, allowing the brain to build new, functional wiring.”
Disorders associated with faulty neuronal circuits include epilepsy, autism, schizophrenia, mental retardation and spasticity and movement disorders, he noted.
During brain development, neurons have to connect to each other, which they do by extending their long axons to touch one another, the researchers explain. Ultimately, the neurons form a circuit between the brain and the target tissue through which chemical and electrical signals are relayed.
In the new study, researchers looked at neurons that travel up the spinal cord into the brain.
“It is very critical that axons are precisely positioned in the spinal cord,” Jaffrey said. “If they are improperly positioned, they will form the wrong connections, which can lead to signals being sent to the wrong target cells in the brain.”
The way that an axon guides and finds its proper target is through “growth cones” located at the tips of axons, he said.
“These growth cones have the ability to sense the environment, determine where the targets are and navigate toward them,” he continued. “The question has always been — how do they know how to do this? Where do the instructions come from that tell them how to find their proper target?”
The researchers found that RNA molecules embedded in the growth cone are responsible for instructing the axon to move left or right, up or down. These RNAs produce antenna-like proteins that steer the axon like a self-guided missile.
“As a circuit is being built, RNAs in the neuron’s growth cones are mostly silent,” he explained. “We found that specific RNAs are only read at precise stages in order to produce the right protein needed to steer the axon at the right time. After the protein is produced, we saw that the RNA instruction is degraded and disappears.”
“If these RNAs do not disappear when they should, the axon does not position itself properly — it may go right instead of left — and the wiring will be incorrect and the circuit may be faulty,” he continued.
The researchers didn’t anticipate that the control of brain wiring is located in these RNA molecules that are “constantly being dynamically turned over,” Jaffrey said.
“This tells us that regulating these RNA degradation pathways could have a tremendous impact on brain development,” he said. “Now we know where to look to tease apart this process when it goes awry, and to think about how we can repair it.”
The study was published in the journal Cell.