What makes us human? The answer may be found in overlooked DNA

 Our DNA is very similar to that of the chimpanzee, which in evolutionary terms is our closest living relative. Stem cell researchers at Lund University in Sweden have now found a previously overlooked part of our DNA, so-called non-coded DNA, that appears to contribute to a difference which, despite all our similarities, may explain why our brains work differently. The study is published in the journal Cell Stem Cell.

The chimpanzee is our closest living relative in evolutionary terms and research suggests our kinship derives from a common ancestor. About five to six million years ago, our evolutionary paths separated, leading to the chimpanzee of today, and Homo Sapiens, humankind in the 21st century.

In a new study, stem cell researchers at Lund examined what it is in our DNA that makes human and chimpanzee brains different -- and they have found answers.

"Instead of studying living humans and chimpanzees, we used stem cells grown in a lab. The stem cells were reprogrammed from skin cells by our partners in Germany, the USA and Japan. Then we examined the stem cells that we had developed into brain cells," explains Johan Jakobsson, professor of neuroscience at Lund University, who led the study.

Using the stem cells, the researchers specifically grew brain cells from humans and chimpanzees and compared the two cell types. The researchers then found that humans and chimpanzees use a part of their DNA in different ways, which appears to play a considerable role in the development of our brains.

"The part of our DNA identified as different was unexpected. It was a so-called structural variant of DNA that were previously called "junk DNA," a long repetitive DNA string which has long been deemed to have no function. Previously, researchers have looked for answers in the part of the DNA where the protein-producing genes are -- which only makes up about two per cent of our entire DNA -- and examined the proteins themselves to find examples of differences."

The new findings thus indicate that the differences appear to lie outside the protein-coding genes in what has been labelled as "junk DNA," which was thought to have no function and which constitutes the majority of our DNA.

"This suggests that the basis for the human brain's evolution are genetic mechanisms that are probably a lot more complex than previously thought, as it was supposed that the answer was in those two per cent of the genetic DNA. Our results indicate that what has been significant for the brain's development is instead perhaps hidden in the overlooked 98 per cent, which appears to be important. This is a surprising finding."

The stem cell technique used by the researchers in Lund is revolutionary and has enabled this type of research. The technique was recognised by the 2012 Nobel Prize in Physiology or Medicine. It was the Japanese researcher Shinya Yamanaka who discovered that specialised cells can be reprogrammed and developed into all types of body tissue. And in the Lund researchers' case, into brain cells. Without this technique, it would not have been possible to study the differences between humans and chimpanzees using ethically defensible methods.

Why did the researchers want to investigate the difference between humans and chimpanzees?

"I believe that the brain is the key to understanding what it is that makes humans human. How did it come about that humans can use their brain in such a way that they can build societies, educate their children and develop advanced technology? It is fascinating!"

Johan Jakobsson believes that in the future the new findings may also contribute to genetically-based answers to questions about psychiatric disorders, such as schizophrenia, a disorder that appears to be unique to humans.

"But there is a long way to go before we reach that point, as instead of carrying out further research on the two per cent of coded DNA, we may now be forced to delve deeper into all 100 per cent -- a considerably more complicated task for research," he concludes.

Source: ScienceDaily

Researchers boost human mental function with brain stimulation

 In a pilot human study, researchers from the University of Minnesota Medical School and Massachusetts General Hospital show it is possible to improve specific human brain functions related to self-control and mental flexibility by merging artificial intelligence with targeted electrical brain stimulation.

Alik Widge, MD, PhD, an assistant professor of psychiatry and member of the Medical Discovery Team on Addiction at the U of M Medical School, is the senior author of the research published in Nature Biomedical Engineering. The findings come from a human study conducted at Massachusetts General Hospital in Boston among 12 patients undergoing brain surgery for epilepsy -- a procedure that places hundreds of tiny electrodes throughout the brain to record its activity and identify where seizures originate.

In this study, Widge collaborated with Massachusetts General Hospital's Sydney Cash, MD, PhD, an expert in epilepsy research; and Darin Dougherty, MD, an expert in clinical brain stimulation. Together, they identified a brain region -- the internal capsule -- that improved patients' mental function when stimulated with small amounts of electrical energy. That part of the brain is responsible for cognitive control -- the process of shifting from one thought pattern or behavior to another, which is impaired in most mental illnesses.

"An example might include a person with depression who just can't get out of a 'stuck' negative thought. Because it is so central to mental illness, finding a way to improve it could be a powerful new way to treat those illnesses," Widge said.

The team developed algorithms, so that after stimulation, they could track patients' cognitive control abilities, both from their actions and directly from their brain activity. The controller method provided boosts of stimulation whenever the patients were doing worse on a laboratory test of cognitive control.

"This system can read brain activity, 'decode' from that when a patient is having difficulty, and apply a small burst of electrical stimulation to the brain to boost them past that difficulty," Widge said. "The analogy I often use is an electric bike. When someone's pedaling but having difficulty, the bike senses it and augments it. We've made the equivalent of that for human mental function."

The study is the first to show that:

• A specific human mental function linked to mental illness can be reliably enhanced using precisely targeted electrical stimulation;
• There are specific sub-parts of the internal capsule brain structure that are particularly effective for cognitive enhancement; and
• A closed-loop algorithm used as a controller was twice as effective than stimulating at random times.

Some of the patients had significant anxiety in addition to their epilepsy. When given the cognitive-enhancing stimulation, they reported that their anxiety got better, because they were more able to shift their thoughts away from their distress and focus on what they wanted. Widge says that this suggests this method could be used to treat patients with severe and medication-resistant anxiety, depression or other disorders.

"This could be a totally new approach in treating mental illness. Instead of trying to suppress symptoms, we could give patients a tool that lets them take control of their own minds," Widge said. "We could put them back in the driver's seat and let them feel a new sense of agency."

The research team is now preparing for clinical trials. Because the target for improving cognitive control is already approved by the Food and Drug Administration for deep brain stimulation, Widge says this research can be done with existing tools and devices -- once a trial is formally approved -- and the translation of this care to current medical practice could be rapid.

"The wonderful thing about these findings is that we are now in a position to conduct clinical trials to further demonstrate effectiveness and then hopefully move to helping treatment-resistant patients who are in desperate need for additional interventions to treat their illnesses," Dougherty said.

This work was supported by grants from the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement Number W911NF-14-2-0045 issued by the Army Research Organization (ARO) contracting office in support of DARPA's SUBNETS Program, the National Institutes of Health, Ellison Foundation, Tiny Blue Dot Foundation, MGH Executive Council on Research, OneMind Institute and the MnDRIVE and Medical Discovery Team on Addiction initiatives at the University of Minnesota Medical School.

Source: Science Daily

Exposure to air pollutants may amplify risk for depression in healthy individuals

 

• Exposure to air pollution is associated with cognitive deficits and an increased risk of depression.
• A recent study examined how air pollutants impact brain networks to mediate changes in cognitive function and enhance the risk of depression.
• The results suggest that genetic susceptibility to depression combined with high levels of exposure to air pollution have a disproportional effect on brain networks involved in cognition and stress.
• Exposure to air pollutants was associated with activation of brain networks expressing depression-associated genes, suggesting that exposure to air pollution may cause adverse mental health effects by acting on the same brain networks related to genetic mechanisms of depression.
• This suggests that individuals with a genetic susceptibility to depression may be more vulnerable to the adverse effects of air pollution on mental health.

Besides having a detrimental effect on physical health, prolonged exposure to air pollutants is also associated with adverse mental healthTrusted Source effects.

Exposure to air pollutants, including fine particulate matter, may be associated with impaired cognitive functioning and depression.

Fine particulate matter, also known as PM2.5, consists of tiny inhalable particles smaller than 2.5 microns. These particles commonly come from industrial sources and vehicles.

How exposure to PM2.5 might increase the risk of depression is not well understood.

Also, scientists do not know whether air pollution can interact with a genetic predisposition for depression to increase the likelihood of depression.

Individuals with a genetic predisposition for a particular disease may have an increased likelihood of developing the condition in the presence of certain environmental factors or due to behaviors such as smoking.

A recent study investigated the effects of PM2.5 exposure, in combination with a genetic predisposition for depression, on brain networks involved in cognition and social stress.

The study’s lead author, Dr. Hao Yang Tan, a scientist at the Lieber Institute in Baltimore, MD, told Medical News Today:

“The study reveals for the first time how air pollution and genes interact with one another to impact important cognitive and emotional circuitry of the brain. Air pollution is changing the expression of genes that are conducive to depression.”

“Previous studies have observed air pollution’s link to depression, but our results are the first to show a direct, neurological cause,” he explained.

“What is most intriguing is that the two factors are linked in such a way that they have a multiplier effect on one’s risk of depression. That is, together, risk genes and bad air raise the risk of depression much more than either factor does in isolation.”

The study appears in the journal Proceedings of the National Academy of Sciences.

Cognition and trait anxiety

The study recruited 352 healthy participants residing in Beijing, China. Beijing has relatively high levels of air pollution, including high concentrations of PM2.5.

For each participant, the researchers studied several specific genetic variants that are associated with depression. From this information, they estimated their genetic susceptibility to depression.

To estimate the PM2.5 exposure levels for each individual, the researchers used air monitoring data obtained from the city air quality monitoring station closest to each person’s home for 6 months before the study.

Depression is associated with cognitive deficits and higher levels of anxiety-depression. In other words, these individuals have an increased tendency to react anxiously or with depressive symptoms to a situation. The scientists evaluated each participant’s levels of anxiety-depression using a questionnaire.

The researchers first examined the effects of PM2.5 exposure on cognition and characteristics associated with depression.

They found that PM2.5 exposure was associated with poor performance on cognitive tests involving reasoning and problem-solving. Higher anxiety-depression was also associated with PM2.5 exposure.

Brain connectivity

Next, the researchers examined brain networks involved in cognition and processing stress-related information and their association with PM2.5 exposure and genetic risk for depression.

The researchers measured the participants’ brain activity while conducting a simple cognitive task using functional magnetic resonance imaging.

To evaluate the influence of social stress on brain activity during the cognitive task, researchers showed the participants the image of a competitor and compared their performance with that of the competitor.

Higher levels of PM2.5 exposure were associated with slower reaction times during the cognitive task, and this effect of PM2.5 exposure became amplified during social stress.

Social stress had a more pronounced effect on brain networks in individuals with a genetic predisposition for depression and greater PM2.5 exposure.

The effect of social stress on brain networks due to the combination of genetic risk and air pollution was greater than the sum of the effects produced by each factor alone. These results suggest that air pollution may interact with genetic risk for depression to influence brain networks.

The dorsolateral prefrontal cortex is a brain region involved in several processes, including cognition. It was one of the key regions whose connectivity changed during the cognitive task in individuals with higher PM2.5 exposure and a genetic predisposition for depression.

Significantly, scientists have observed changes in the dorsolateral prefrontal cortex activity of healthy individuals with a genetic predisposition for depression and individualsTrusted Source with depression.

Depression-related brain networks

To further examine the interaction between genetic risk for depression and air pollution, the researchers investigated whether the combination of these factors differentially influenced brain networks involved in depression.

The researchers mapped the brain networks involved in depression by identifying brain regions expressing high levels of depression-associated genes.

The researchers used the online database Allen Brain Atlas, which provides detailed gene expression data for brain regions. They then identified brain regions that showed correlated expression of genes associated with depression.

The researchers examined if this pattern of coexpression of depression-associated genes in brain regions obtained using the atlas was similar to the brain connectivity patterns of the participants during the cognitive tests.

The pattern of coexpression of depression-associated genes derived using the atlas predicted brain connectivity patterns observed during the cognitive task. However, this was only the case for those with greater exposure to PM2.5 levels and a higher genetic predisposition for depression.

The correlation was weaker in individuals with a lower genetic risk of depression or lower exposure to PM2.5.

This suggests that exposure to PM2.5 air pollutants affects brain network functions associated with the genetic mechanisms of depression.

The researchers also conducted similar analyses focused on the association between the connectivity patterns of the dorsolateral prefrontal cortex with other brain regions and the coexpression of depression-associated genes in these regions.

The co-expression of depression-associated genes tracked the connectivity patterns to and from the dorsolateral prefrontal cortex in individuals with a genetic risk for depression, higher PM2.5 exposure levels, or both.

Interestingly, the co-expressed genes that correlated with brain connectivity patterns of the prefrontal cortex included some involved in neuroinflammation.

Depression is associatedTrusted Source with chronic, low-grade inflammation, further suggesting that PM2.5 exposure may interact with depression-associated genes to increase the risk of depression.

“This is possibly the first study to directly implicate how genes for brain disorders operate in concert with each other and affect important cognitive and emotional functions in the live functioning brain, and the impact of air pollution and genes in multiplying the effects of each on these brain functions,” Dr. Tan told MNT.

“It is now [in] much less doubt that there are direct impacts of air pollution on how genes operate in the brain to affect risk for these neuropsychiatric disorders,” he added.

Source: Medical News Today

Harnessing the skin’s microbiome could help combat skin aging

 

• A recent study published in the journal PLOS OneTrusted Source has identified bacterial pathways associated with skin aging.
• The data demonstrated that the main bacterial pathways related to aging involve the production of skin pigment, fatty acids, and ceramides.
• Better understanding the molecular processes that drive skin aging and their relationship with the microbiome will require further research.
• Data from prospective studies may help develop effective treatments to combat skin aging.

Bacteria, fungi, and viruses live on the skin and in the gut. The skin is the body’s largest organ, and it serves as a protective barrier from the outside environment.

Commensal microbial communities on the skin, also known as the skin microbiome, do not cause disease and benefit the body. They may be fixed or exist temporarily on the skin.

The skin microbiome interacts with the body’s immune system and may affect its functioning. And the immune system regulates the makeup of the skin microbiome.

Aging causes changes to the skin’s structure and function. This may result from “intrinsic” factors, such as hormonal, metabolic, or immune system changes. “Extrinsic” factors, such as smoking and exposure to sunlight and certain temperatures, may also trigger immune processes that affect the skin’s structure and rejuvenation.

Increased wrinkles, decreased elasticity, reduced wound healing, and impaired barrier function are skin changes that occur during aging.

Changes in the skin microbiome can also stem from a decline in the production of sebum, which is an oily substance that protects the skin, as well as from decreased water content in the skin and immune dysfunction.

Age-related microbiome changes

Advanced scientific methods called 16S ribosomal RNA geneTrusted Source and metagenomic sequencing techniques are now available to assess changes in the skin’s microbes caused by aging.

Dr. Elizabeth Grice, an associate professor of dermatology and microbiology at the University of Pennsylvania, explained in a 2019 lecture that the 16S ribosomal RNA sequencing technique allows us to “answer the questions [about] the composition of a sample or the diversity of a sample.”

She went on to say that “Shotgun metagenomics provides a more nuanced view of the skin microbiome. Using these methods, one can take a sample containing the genomic DNA, […] break up that DNA in the sample, and then sequence those fragments. This allows one to identify microbes to the species and strain level, it allows one to reconstruct the genetic and functional metabolic pathways within a sample and, importantly, it gives you a multi-kingdom view of the skin microbiome.”

Previous studies have demonstrated that the skin microbiomes of all humans consistently contains certain species of Staphylococcus, Cutibacterium, Corynebacterium, and Acinetobacter bacteria.

However, age, body area, gender, and geographic location affect the composition of the skin microbiome. Although previous studies had identified changes in the makeup of the skin microbiome related to aging, researchers had yet to fully understand the mechanisms behind these changes.

In a new study, a team from NIZO Food Research, in the Netherlands, set out to understand the connection between the body’s cellular processes, called co-metabolism, and genes, or bacterial functionalities, involved in skin aging. Estée Lauder, a company that sells skincare products, partially funded the study.

First, the researchers searched existing scientific literature to identify common biologic pathways between humans and skin microbes linked to intrinsic skin aging. They then used 16S ribosomal RNA sequencing testing from cheek samples of female participants with various age-related skin changes to confirm the changes to the skin microbiome composition seen in selected studies.

The team took skin swab samples, one from each cheek, from 25 healthy female participants of European descent in Belgium. The participants fell into two age groups, one aged 20–28, and the other aged 59–68.

The study excluded participants with certain skin conditions and external factors related to skin aging. Some of the exclusion criteria included:

• acne
• eczema
• psoriasis
• use of skin medications, such as antibiotics, antifungals, or steroids, within 1 month of the study
• smoking, or a history of smoking in the past 2 years
• tanning or sunbathing
• drinking more than 3 servings of alcohol per day

Skin aging bacterial pathways

The researchers gathered reference genomesTrusted Source from the gene sequences database of the National Center for Biotechnology InformationTrusted Source. The information concerned genes relevant to skin aging, as identified and confirmed by testing.

The team then used microbial pathways to create graphical models, which they used to analyze the reference skin organism genomes, 16S ribosomal RNA sequencing testing, and data from the direct analysis of genomes from the collected skin samples.

The group found that bacterial pathways linked to skin aging were related to the production of ceramides, which are lipids that compose the natural skin barrier, as well as fatty acids and pigmentation. The researchers also determined that bacterial enzymesTrusted Source involved in protein glycation were associated with skin aging.

Protein glycation in the skin occurs when sugars link to proteins, such as collagen and elastin. An accumulation of glycation of collagen and elastin end products can resultTrusted Source in loss of skin elasticity and sagging.

One limitation of the study, however, is its small size and lack of diversity, which may limit the generalizability of its findings.

Overall, the results may serve as a basis for future studies seeking to improve our understanding of the interplay of molecular processes and the microbiome in skin aging.

Dr. Bierman described the study as a good starting point, but added that “A lot of research [is needed] before we can actually, for sure, say what the different bacteria are doing and how they interact with each [other], too, and might influence how our skin ages.”

Source: Medical News Today

Adolescent depression: Could school screening help?

 

• In the United States, depression among adolescents has been increasing.
• As most adolescents attend schools, they can be useful places to identify students with depressive symptoms.
• In a new study, universally screening students for depression was more effective in identifying students and getting them to start treatment than teachers flagging changes in behavior that might suggest depression.

A new study investigates the effects of universally screening students for depression in schools. The researchers conclude that this screening is a more successful approach than simply relying on teachers to report behavior that might indicate depression.

The study, which appears in the journal JAMA Network OpenTrusted Source, offers a new way to respond to the significant rise in depression in U.S. adolescents since 2008.

Depression

According to the National Institute of Mental Health (NIMH)Trusted Source, depression is a common but serious mood disorder that can have profound negative effects on quality of life.

The symptoms vary among individuals but can include:

• feeling sad, anxious, emotionally empty, irritable, restless, or hopeless
• speaking slowly
• having low energy
• having disrupted sleep
• finding it difficult to concentrate
• having suicidal thoughts

Depression is a condition that can affect people of different ages, including adolescents. According to the NIMHTrusted Source, in 2019 — the most recent year for which data are available — 15.7% of adolescents in the U.S. had at least one major depressive episode.

This number has almost doubled from the 2008 figure of 8.3%.

Screening for depression

In 2009, the Preventive Services Task Force suggested that primary care services should screen all adolescents for depression. However, this has not been achieved in practice.

The researchers behind the present study note that there are significant disparities in who is able to access primary healthcare, with more than 60% of adolescents not receiving routine preventive healthcare. There are also inequalities based on region and inequities due to race and ethnicity.

Schools can be a good place to identify adolescents who may be experiencing depression, as most adolescents attend school.

Schools in the U.S. currently universally screen for some physical health problems. However, mental health issues such as depression depend on the staff at schools flagging behavior that may suggest depression to the relevant services.

Speaking with Medical News Today, Dr. Deepa Sekhar — a pediatrician at Penn State Health Children’s Hospital, Hershey, and the corresponding author of the present study — said that “the current approach depends upon adolescents exhibiting symptoms/acting out in some way, e.g., failing classes, missing classes, [or] irregular behavior.”

In the study, Dr. Sekhar and her colleagues wanted to see whether universally screening for depression in schools would result in the identification and treatment of more students with possible depression compared with a targeted model.

According to Dr. Sekhar, “Our study is publishing at a time when more adolescents are reporting symptoms of depression.”

“From 2008 to 2018, the numbers increased by over 70% from 8.3% to 14.4%. During the pandemic, concerns about increasing student depression have been widespread. Suicides, which are often associated with mental health conditions, are now the second leading cause of adolescent death,” said Dr. Sekhar.

Almost 13,000 participants

The study, known as Screening in High Schools to Identify, Evaluate, and Lower Depression (SHIELD), took place between November 6, 2018, and November 20, 2020, in public high schools in Pennsylvania.

A total of 12,909 students from 14 different high schools took part.

The researchers randomized each school so that either students from the 9th and 11th grades or those from the 10th and 12th grades received universal screening.

Staff members continued to flag students in the other grades if and when they noticed depression-related behavior. They were also able to use this conventional method for students who were undergoing universal screening.

The students who underwent universal screening filled in the Patient Health Questionnaire-9 — a well-established questionnaire for screening depression. They did this electronically during school hours.

Significant identification of depression

During the study, 1,226 students — 9.5% of the study participants — met the criteria for major depressive disorder. Of these, 1,026 came from the universal screening group, with the remaining 200 coming from the group undergoing the usual targeted screening.

After an initial assessment from student support staff, 233 students from the universal screening group warranted a follow-up, and 80 of these individuals went on to begin treatment.

In comparison, 64 of the targeted screening group warranted a follow-up, with 35 beginning treatment.

According to these findings, students who underwent universal screening were 5.9 times as likely to have their major depressive disorder symptoms identified and 2.1 times as likely to initiate the recommended treatment.

Dr. Sekhar said to MNT that universal screening could also potentially be useful for other common mental health issues, but only if schools have the resources to support students identified as having mental health issues.

“Screening should not be done unless you know that intervening for identified students is effective and [you also] have the capacity to intervene,” said Dr. Sekhar.

“Take vision screening — we know glasses can help kids who can’t see well, but it would not make any sense for a school district to screen if there was no way for identified students to get glasses.”

Future research

The researchers plan to further their work. Dr. Sekhar said to MNT that “[o]ur next step is to consider how we can best support schools with an interest in universal screening to successfully implement this practice.”

In an invited commentaryTrusted Source on the research, Dr. Sisi Guo, from the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles, and Dr. Grace Bai Jhe, from the Division of Adolescent/Young Adult Medicine at Boston Children’s Hospital, noted the significance of the research while also identifying further questions that need answering.

For Dr. Guo and Dr. Jhe, future research could explore the extent to which universal screening can identify adolescents with subclinical symptoms. It could also investigate whether students that universal screening procedures identify continue to engage with treatment after the first session.

Dr. Guo and Dr. Jhe also highlighted that while universal screening may be effective in identifying adolescents with major depressive disorder, schools need to be well-funded and resourced to be able to respond to this information.

As they write, “both longstanding and newfound, more equitable funding and policies are necessary to ensure that staff are adequately trained, and schools remain accessible to all youth.”

Source: Medical News Today

Multiple sclerosis drug may alleviate Alzheimer’s memory loss

 

• A drug doctors use to treat multiple sclerosis may be effective in treating Alzheimer’s symptoms, including memory loss.
• In mice, memory improved after 8 weeks of treatment with the drug.
• The treated mice also showed a reduction in amyloid plaques.
• Clinical trials are needed to show whether the drug, glatiramer acetate, can slow the development of Alzheimer’s disease.

Alzheimer’s disease (AD) affects 1 in 9 people aged 65 and older in the United States and 1 in 14 people in this age group in the United Kingdom. Memory loss is one of the most troubling symptoms of AD. A study published in Frontiers in Neuroscience has found that a drug used to treat multiple sclerosis (MS) may help alleviate this symptom.

Researchers from the Del Monte Institute for Neuroscience at the University of Rochester, NY, carried out the study in mice. The scientists gave the drug, glatiramer acetate (GA)Trusted Source, to transgenic 3xTg-AD mice for 8 weeks, then assessed their memory skills.

The mice that researchers used in the trial were 15-month-old females. These transgenicTrusted Source mice have three mutations associated with AD. They develop the characteristic plaque and tangle pathology of AD by around 12 months of age.

Researchers gave the trial mice subcutaneous injections of GA for 8 weeks. One control group received injections of phosphate-buffered saline (PBS). Wild-type mice made up two other control groups, one receiving GA, the other PBS.

“GA has been used for many years to treat MS. It appears to modify T cell responses, so the immune response is less aggressive, but we don’t really understand the mechanism,” said Dr. Michael O’Banion, M.D., Ph.D., professor of neuroscience, and senior author of the study.

After 8 weeks, researchers assessed memory skills in the mice. They also analyzed their brain tissue to look for changes in the microgliaTrusted Source, amyloid plaquesTrusted Source, and tau tanglesTrusted Source.

Improved memory

Researchers tested the memory skills of the mice using Novel Object Recognition (NOR)Trusted Source. They first allowed the mice to investigate two objects in a box, then removed the mice from the box. The scientists left one object, the “familiar object,” inside the box and changed the other, the “novel object.”

They returned the mice to the box 2 hours later and scored them on how much time they spent exploring each object. The researchers saw a preference for the novel object as an indication of memory.

After 8 weeks, performance in NOR was markedly improved in the transgenic mice that the researchers had given GA compared with those on PBS. The performance of the GA-treated mice was comparable to the performance of the wild-type mice.

“Rodents are naturally curious. One interpretation is that [the GA-treated mice] have recovered a normal mouse behavior, which is to investigate a novel object,” Dr. O’Banion said.

Subtle changes

The study saw some changes in brain morphology, which might indicate why memory improved after GA treatment.

“In transgenic mice [with AD], the microglia show morphologies consistent with being more activated, responding to something that’s not right. In the GA mice, we saw subtle changes. The microglia were less activated,” Dr. O’Banion said.

“We also found modest changes in gene expression that suggested the GA was altering the immune activation,” he added. “A caveat is that if you improve the pathology, you should see less microglia activation — it’s an association, not a cause and effect.”

First steps

These findings in mice genetically engineered to have AD could be a step towards using GA as a treatment for the condition in people.

Dr. Verna R. Porter, M.D., a neurologist and director of programs for dementia, Alzheimer’s disease, and neurocognitive disorders at the Pacific Neuroscience Institute, an affiliate of Providence Saint John’s Health Center in Santa Monica, CA, commented: “This is a preliminary study in a murine [or] mouse model. This study does lend credence to the notion that therapies that effectively modulate the immune system could be effective in our fight against Alzheimer’s disease.”

This study replicated earlier work showing the benefits of GA in Alzheimer’s mouse models, but Dr. O’Banion urged caution in interpreting their findings: “It is important to recognize that there was an association of benefits in a cognitive test and Alzheimer’s pathological hallmarks. The question remains whether the glatiramer affecting microglia led to the improvement.”

Call for clinical trials

The researchers plan to conduct more mouse studies to see whether they can replicate these findings but would like the drug to go into clinical trials.

“Here we have a drug that has been used in people for over 15 years, so maybe it is something that should be tried in a clinical trial,” Dr. O’Banion said.

Dr. Snyder echoed this sentiment: “Since scientists are building on previous research, much is already known about the drug’s potential side effects. It may take less time for the drugs to be tested, and the clinical trials may be less expensive.”

Source: Medical News Today

Scientists identify new cause of vascular injury in type 2 diabetes

 

• MicroRNA-210, which is present in healthy red blood cells, helps regulate vascular function.
• A new study shows that there is a lower level of microRNA-210 in the red blood cells of people with type 2 diabetes.
• Replenishing levels of microRNA-210 may one day prevent vascular injury associated with this type of diabetes.

Among the many complications of type 2 diabetes, the development of cardiovascular disease and poorer clinical outcomes following cardiovascular events, especially heart attacks, may be of particular concern.

A recent study published in the journal DiabetesTrusted Source suggests that a lack of a specific molecule in red blood cells may be the root of type 2 diabetes-induced vascular complications.

In recent years, research has shown that these specialized cells undergo several changes and can become dysfunctional in people with this form of diabetes.

Changes in red blood cells

Red blood cells carry oxygen from the lungs to the rest of the body. They also transport carbon dioxide back to the lungs for exhalation. In a lesser-known but equally crucial role, red blood cells have an influence on maintaining cardiovascular equilibriumTrusted Source, or homeostasis. This is partly achieved through the production of nitric oxide.

The body uses nitric oxide to widen blood vessels. And researchersTrusted Source have noted that red blood cells in people with type 2 diabetes have a reduced ability to produce nitric oxide. This can lead to the constriction of coronary arteries.

Type 2 diabetes can also affect the releaseTrusted Source of adenosine triphosphate by red blood cells. This is the primary molecule for storing and transferring energy within the body.

Another change in the red blood cells of people with diabetes is an increased formation of reactive oxygen species. The presence of these molecules can lead to more plaque formation on the interior walls of arteries, a health problem called atherosclerosis.

In the new study, researchers at the Karolinska Institutet, in Sweden, investigated which molecular changes within red blood cells could explain these dysfunctions. The team recruited 36 participants with type 2 diabetes and 32 healthy participants who did not take medication and had normal fasting glucose levels and no history of cardiovascular disease.

The importance of microRNA-210

The researchers found that the red blood cells of those with type 2 diabetes had much less microRNA-210 than those of the healthy participants. MicroRNA molecules occur naturally and regulate cellular functions, including vascular activity.

The study showed that the reduction in microRNA-210 caused changes in specific vascular protein levels. These alterations contributed to the development of endothelial dysfunction. The endothelium is the thin membrane that lines the heart and blood vessels.

The researchers also found that atherosclerotic plaques taken from participants with type 2 diabetes had lower levels of microRNA-210 than those from the healthy participants.

In addition, glycemic control through medication appeared to have no major influence on the detrimental effects of the changes to red blood cells in participants with type 2 diabetes.

Possible future treatment

Dr. Swapnil Khare, an assistant professor of clinical medicine and medical director of inpatient diabetes at Indiana University School of Medicine, shared her thoughts on the study with Medical News Today. She was not involved in the research.

“They showed in a part of the study that if they replace the microRNA, the endothelial dysfunction did improve,” Dr. Khare explained. “I would say this isn’t a surprising study, but definitely exciting.”

The direct relationship between microRNAs and red blood cells has yet to be completely understood. The study authors acknowledge that clarifying the signaling pathways between these biostructures will require further research.

In the conclusion to the study paper, the researchers write that increasing red blood cell microRNA-210 levels has the potential to be an effective treatment for endothelial dysfunction and help prevent vascular injury in people with type 2 diabetes.

Source: Medical News Today