Tag: inflammation

Categories : Mental HealthTags :

Histamine Involvement in Depression Revealed

On By ModernMedia
Image by Falkurian Design on Unsplash

Histamine from inflammation dampens serotonin levels and antidepressants’ ability to boost them, according to experiments in mice models.

The findings, published in The Journal of Neuroscience add to mounting evidence that inflammation, and the accompanying release of the molecule histamine, affects serotonin, a key molecule responsible for mood in the brain.

Inflammation triggers the release of histamine in the body, increasing blood flow to affected areas to flood them with immune cells. While these effects help the body fight infections, both long-term and acute inflammation is increasingly linked to depression. There is already strong evidence that patients with both depression and severe inflammation are the ones most likely not to respond to antidepressants.

Dr Parastoo Hashemi, Lead Author, Imperial’s Department of Bioengineering, said: “Our work shines a spotlight on histamine as a potential key player in depression. This, and its interactions with the ‘feel-good molecule’ serotonin, may thus be a crucial new avenue in improving serotonin-based treatments for depression.”

Chemical messengers
Serotonin is a key target for depression-tackling drugs, and selective serotonin reuptake inhibitors (SSRIs) inhibit the re-absorption of serotonin in the brain, allowing it to circulate for longer and improve mood.

However, although SSRIs bring relief to many who take them, an increasing number of people are resistant to it. This could be due to the specific interactions between chemical messengers, or neurotransmitters, including serotonin and histamine.

With this in mind, researchers set out to investigate the relationship between histamine, serotonin, and SSRIs. They created tiny serotonin-measuring microelectrodes and put them into the hippocampus of the brains of live mice, an area known to regulate mood. The technique, known as fast scan cyclic voltammetry (FSCV), allowed them to measure brain serotonin levels in real time..

After placing the microelectrodes, they injected half the mice with lipopolysaccharide (LPS), an inflammation-causing toxin found in some bacteria, and half the mice with a saline solution as a control.

Within minutes of LPS injection, brain serotonin levels dropped, whereas they remained the same in control mice, demonstrating the rapid action of inflammatory responses on the brain and serotonin. Since LPS cannot cross the blood-brain barrier, it could not cause the drop in serotonin.
The inflammatory response triggered histamine in the brain which directly inhibited the release of serotonin by attaching to inhibitory receptors. 

To counter this, the researchers administered SSRIs to the mice, but they were much less able to boost serotonin levels than in control mice. They posited that this is because the SSRIs directly increased the amount of histamine in the brain, cancelling out its serotonin boosting action.

The researchers then administered histamine reducing drugs alongside the SSRIs to counter histamine’s inhibitory effects, and saw serotonin levels rise back to control levels. This appears to confirm the theory that histamine directly dampens serotonin release in the mouse brain. These histamine reducing drugs cause a whole-body reduction in histamine and are distinct from antihistamines taken for allergies, which block histamine’s effects on neurons.

A new molecule of interest
More work is needed before progressing to human studies. However, it is not currently feasible to use microelectrodes to make similar measurements in human brains, so the researchers are now looking at other ways to get a snapshot of the brain by looking at other organs which use serotonin and histamine, like the gut.

Source: Imperial College London

Categories : Diseases, Syndromes and ConditionsTags :

New Insights into Gum Disease and Inflammatory Response

On By ModernMedia
Photo by Caroline LM on Unsplash
Photo by Caroline LM on Unsplash

A team of researchers has identified how different people respond to the accumulation of dental plaque, helping us understand the vulnerability of some to serious conditions that lead to tooth loss and other problems. 

The study was led by University of Washington researchers and recently published in the journal Proceedings of the National Academy of Sciences (PNAS). 

Buildup of plaque, the sticky biofilm covering teeth and gums, can induce gingivitis, or gum inflammation if left unchecked. Gingivitis, in turn, can lead to periodontitis, a serious infection that can damage and destroy the gum and bones supporting teeth. As well as causing tooth loss, this chronic inflammation can also trigger heart disease, diabetes, cancer, arthritis, and bowel diseases.

The researchers also discovered a range of inflammatory responses to oral bacterial accumulation. When bacteria build up on tooth surfaces, it generates inflammation as the body responds. Two known major oral inflammation phenotypes were known: a high or strong clinical  response and a low clinical response. The team identified a third phenotype, which they dubbed ‘slow’: a delayed strong inflammatory response in the wake of the bacterial buildup.

The study also found that subjects with low clinical response also showed a low inflammatory response for a variety of inflammation signals.  “Indeed, this study has revealed a heterogeneity in the inflammatory response to bacterial accumulation that has not been described previously,” said Dr Richard Darveau of the UW School of Dentistry, one of the study’s authors.

Study co-author Dr Jeffrey McLean said, “We found a particular group of people that have a slower development of plaque as well as a distinct microbial community makeup prior to the start of the study.” The authors wrote that understanding the variations in gum inflammation could help screen for higher periodontitis risk. In addition, it is possible that this variation in the inflammatory response among the human population may be related to the susceptibility to other chronic bacterial-associated inflammatory conditions such as inflammatory bowel disease.

Additionally, the researchers found a novel protective response by the body, triggered by plaque accumulation, that can save tissue and bone during inflammation. This mechanism, which was apparent among all three phenotypes, utilises white blood cells known as neutrophils. In the mouth, they act something like cops on the beat, patrolling and regulating the bacterial population to maintain a stable condition known as healthy homeostasis.

In this instance, plaque is not a villain. To the contrary, the researchers said that the proper amount and makeup of plaque supports normal tissue function. Studies in mice have also shown that plaque also provides a pathway for neutrophils to migrate from the bloodstream through the gum tissue and into the crevice between the teeth and gums.

When healthy homeostasis exists and everything is working right, the neutrophils promote colonization resistance, a low-level protective inflammatory response that helps the mouth fend off an excess of unhealthy bacteria and resist infection. At the same time, the neutrophils help ensure the proper microbial composition for normal periodontal bone and tissue function.

The researchers’ findings underscore why dentists preach the virtues of regular brushing and flossing, which prevent too much plaque buildup. “The idea of oral hygiene is to in fact recolonise the tooth surface with appropriate bacteria that participate with the host inflammatory response to keep unwanted bacteria out,” Dr Darveau explained. The bacteria start repopulating the mouth’s surfaces spontaneously and almost immediately afterward, Dr Darveau said.

Source: University of Washington School of Dentistry

Journal information: Bamashmous, S., et al. (2021) Human variation in gingival inflammation. PNAS. doi.org/10.1073/pnas.2012578118.

Categories : Ageing Immune SystemTags :

Chronic Inflammation Ages the Pituitary Gland in Mice

On By ModernMedia
Photo by Robina Weermeijer on Unsplash

Researchers have discovered that the pituitary gland in mice ages due to an age-related form of chronic inflammation — which raises the possibility of slowing or even partially repairing this process. 

The pituitary gland is a small, globular gland located underneath the brain that plays a major role in the hormonal system, explained Professor Hugo Vankelecom, a stem cell biologist from the Department of Development and Regeneration at KU Leuven. “My research group discovered that the pituitary gland ages as a result of a form of chronic inflammation that affects tissue and even the organism as a whole,” he said. “This natural process usually goes unnoticed and is referred to as ‘inflammaging’ — a contraction of inflammation and ageing. Inflammaging has previously been linked to the ageing of other organs.”

Because of the pituitary’s pivotal role in the body, its ageing may contribute to the reduction of hormonal processes and hormone levels in our body – such as in menopause.

The study also provides significant insight into the stem cells in the ageing pituitary gland. In 2012, Prof Vankelecom and colleagues showed that a prompt reaction of these stem cells to injury in the gland leads to repair of the tissue, even in adult animals.

“As a result of this new study, we now know that stem cells in the pituitary do not lose this regenerative capacity when the organism ages. In fact, the stem cells are only unable to do their job because, over time, the pituitary becomes an ‘inflammatory environment’ as a result of the chronic inflammation. But as soon as the stem cells are taken out of this environment, they show the same properties as stem cells from a young pituitary.”

Could damage be repaired?

This insight opens up a number of potential therapeutic avenues: would it be possible to reactivate the pituitary? This wouldn’t just involve slowing down hormonal ageing processes, but also repairing the damage caused by a tumour in the pituitary, for example. 

“No fewer than one in every 1000 people is faced with this kind of tumour — which causes damage to the surrounding tissue — at some point.

“The quality of life of many of these patients would be drastically improved if we could repair this damage. We may be able to do so by activating the stem cells already present — for which our present study also provides new indications — or even by transplanting cells. That said, these new treatment options are not quite around the corner just yet, as the step from fundamental research to an actual therapy can take years to complete. For the time being, our study sets out a potential direction for further research.”

The study also brings up another interesting approach: using anti-inflammatory drugs to slow down pituitary ageing or even rejuvenate an ageing pituitary. “Several studies have shown that anti-inflammatory drugs may have a positive impact on some ageing organs. No research has yet been performed on this effect in relation to the pituitary.”

From mice to humans

Since Prof Vankelecom and colleagues studied the pituitary of mice, further research is required to demonstrate whether their findings also apply to humans. Prof Vankelecom cautioned, however: “Mice have a much greater regeneration capacity than humans.

“They can repair damaged teeth, for instance, while humans have lost this ability over the course of their evolution. Regardless, there are plenty of signs suggesting that pituitary processes in mice and humans are similar, and we have recent evidence to hand that gene expression in the pituitaries of humans and mice is very similar. As such, it is highly likely that the insights we gained will equally apply to humans.”

Source: KU Leuven

Journal information: Vennekens, A., et al. (2021) Interleukin-6 is an activator of pituitary stem cells upon local damage, a competence quenched in the aging gland. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2100052118.

Categories : Mental HealthTags :

Inflammation a Predictor of Future Depression in Widowed Spouses

On By ModernMedia

Researchers at Rice University have found that future depression in widowed spouses can be predicted by bodily inflammation after the death of their partners.

The study will be published in the June 2021 edition of the journal Psychoneuroendocrinology. The study was led by lead author Lydia Wu, a Rice psychology graduate student, and Christopher Fagundes, associate professor of psychology and principal investigator for the Biobehavioral Mechanisms Explaining Disparities (BMED) lab at Rice. The researchers recruited 99 participants who had lost their spouses within 2-3 months of the study, and evaluated them on a number of factors, including physical and mental health, over three months.

“Prior research has already linked bodily inflammation to a host of health issues, including cancer, memory issues, heart problems and depression,” Wu said. “We were interested in how systemic inflammation affects the mental health of spouses after losing a loved one. In particular, can inflammation help us identify who will experience clinical levels of depression at a future point in time?”

The researchers found that widowed spouses with higher levels of bodily inflammation immediately after the loss of their partners had more severe symptoms of depression three months later compared to those with lower inflammation levels. This was even more pronounced if they didn’t experience significant depression initially.

Prof Fagundes said that it is normal to experience depression following the death of a spouse, and research shows that undergoing psychotherapy right after the event can actually interfere with people’s natural coping ability.

“We know that most people are remarkably resilient,” he said.

In the case of persistent depression, or depression occurring six or more months after a spouse’s death, it may be a sign that clinical intervention is needed, Prof Fagundes said.

“Until this study, it was difficult to know who was at risk for these persistently high levels of depression and grief until the six-month mark,” he said. “This study identifies a potential biomarker that could help us predict who is at greatest risk for long-term repercussions of loss.”

“This information makes early intervention possible,” Wu said. “We can identify at-risk bereaved persons and introduce them to interventions early on to improve their mental health.”

The researchers said more research is needed to determine who might be at greatest risk.

Source: Rice University

Journal information: E. Lydia Wu et al, Inflammation and future depressive symptoms among recently bereaved spouses, Psychoneuroendocrinology (2021). DOI: 10.1016/j.psyneuen.2021.105206

Categories : Immune SystemTags :

Tropical Ginger Can Block Inflammation

On By ModernMedia
A piece of ginger. Photo by Lawrence Aritao on Unsplash

New research has shown how compound found in the tropical ginger plant, 1′-acetoxychavicol acetate, or ACA, can have an anti-inflammatory effect.

Researchers found that ACA reduces mitochondrial damage by lowering levels of mitochondrial reactive oxygen species (ROS), blocking activation of a crucial protein complex known as the NLRP3 inflammasome. A number of inflammatory diseases, like inflammatory bowel disease, display improper and chronic activation of this complex.

It has been suggested by previous studies that the NLRP3 inflammasome plays a significant role in promoting inflammation by secreting a molecule called IL-1β. This molecule works as a messenger, sending various immune cells to the site of injury or infection. Further studies detailed how production of ROS can help to trigger the NLRP3 inflammasome. Because other groups showed that the ginger compound ACA can reduce ROS production in certain immune cells, the researchers wondered how this compound would affect the way NLRP3 inflammasome worked.

“Many disease pathogeneses involve dysregulation of the inflammasome,” commented Daisuke Ori, co-lead author on the study. “Blood cells from people suffering from rheumatoid arthritis or other autoimmune disorders frequently have increased levels of inflammasome-derived IL-1β. Therefore, targeting the NLRP3 inflammasome with a compound like ACA may be a promising therapeutic strategy.”

The researchers took immune cells from mouse bone marrow, and also used a mouse model of colitis. ACA was added to the growing cells and the compound was added to their mice’s food. The researchers then looked at the effects on ROS production, secretion of IL-1β, and other markers of inflammation.

“Cells treated with ACA had significantly reduced IL-1β production, as well as lower levels of ROS,” explained senior author Taro Kawai. “ACA could also inhibit NLRP3 inflammasome activation in the colitis mouse model.” These in vivo results are promising, as they suggest ACA has the potential to treat or prevent the development of inflammatory diseases. “Interestingly, we did not observe high levels of immune cell death when using ACA, which means that it may be relatively safe,” continued Ori.

The study provided novel evidence for a specific molecular mechanism governing the previously observed anti-inflammatory properties of ACA. The study also showed the potential of ACA for therapeutic use in diseases mediated by IL-1β molecules, or associated with cytokine storms, as seen in patients suffering from severe COVID.

Source: Medical Xpress

Journal information: Sophia P M Sok et al. 1′-acetoxychavicol acetate inhibits NLRP3-dependent inflammasome activation via mitochondrial ROS suppression, International Immunology (2021). DOI: 10.1093/intimm/dxab016

Categories : Ageing Cardiovascular Disease Neurodegenerative DiseasesTags :

Mitochondria Dump DNA into Cells, Triggering Inflammation

On By ModernMedia

Researchers have discovered that when building blocks for DNA in cells are in short supply, mitochondria— the powerhouses of cells — release their own DNA, triggering an inflammatory response. Targeting this process can now open up new avenues of treatment into ageing-related diseases.

Mitochondria, the producers of energy for cells, , have their own genetic material: mitochondrial DNA. In certain situations, however, mitochondria are known to release their DNA into the interior of the cell, provoking a reaction from the cell’s own immune system. Some cardiac and neurodegenerative diseases as well as the ageing process are associated with the mitochondrial genome.

To find out when mitochondria release their DNA, the researchers have focused on the mitochondrial protein YME1L. “In cells lacking YME1L, we observed the release of mitochondrial DNA into the cell interior and a related immune response in the cells,” explained Thomas MacVicar, one of the study’s two first authors.  
“If the cells lack YME1L, there is a deficiency of DNA building blocks inside the cell,” he continued. “This deficiency triggers the release of mitochondrial DNA, which in turn causes an inflammatory response in the cell: the cell stimulates similar inflammatory reactions as it does during a bacterial or viral infection. If we add DNA building blocks to the cells from the outside, that also stops the inflammation.”

This newly discovered link between cellular inflammatory response and the metabolism of DNA building blocks could have far-reaching consequences, MacVicar explained. “Some viral inhibitors stop the production of certain DNA building blocks, thereby triggering an inflammatory response. The release of mitochondrial DNA could be a crucial factor in this, contributing to the effect of these inhibitors,” he said. 
Mitochondrial DNA is associated with a number of ageing-associated inflammatory diseases, including cardiac and neurodegenerative diseases, as well as obesity and cancer. The authors hope that new therapeutic opportunities in such diseases can be created by modulating the metabolism of DNA building blocks.

Source: Medical Xpress

Journal information: Hans-Georg Sprenger et al, Cellular pyrimidine imbalance triggers mitochondrial DNA–dependent innate immunity, Nature Metabolism (2021). DOI: 10.1038/s42255-021-00385-9

Categories : GastrointestinalTags :

A Fungus in Certain Foods Slows Intestinal Healing

On By ModernMedia

A study has found that a fungus found in certain foods such as cheese and processed meats can cause intestinal injuries in humans and mice with Crohn’s disease to fester and impeding healing.

These findings, from researchers at Washington University School of Medicine in St. Louis and the Cleveland Clinic, suggest that there is potentially a diet-based way to treat Crohn’s disease.

“We’re not suggesting that people stop eating cheese and processed meat; that would be going far beyond what we know right now,” said first author Umang Jain, PhD, an instructor in pathology & immunology at the School of Medicine. “What we know is that this foodborne fungus gets into inflamed, injured tissue and causes harm. We’re planning to perform a larger study in people to figure out if there’s a correlation between diet and the abundance of this fungus in the intestine. If so, it is possible dietary modulation could lower levels of the fungus and thereby reduce symptoms of Crohn’s disease.”

Crohn’s disease is driven by chronic inflammation in the gastrointestinal tract and immunosuppressive medication is the usual treatment. Crohn’s patients endure flare-ups where digestive tracts are dotted with inflamed, open sores that can persist for up to months.

To understand why intestinal ulcers heal so slowly in some people, the researchers studied mice with injured intestines. By sequencing microbial DNA at the site of injury, they discovered that the fungus Debaryomyces hansenii was abundant in wounds but not in uninjured parts of the intestine. D. hansenii can be found in all kinds of cheeses, as well as sausages, beer, wine and other fermented foods.

Introducing D. hansenii into mice with injured intestines slowed down the healing process, and eliminating the fungus with amphotericin B sped it up. In humans, the researchers discovered  D. hansenii in seven out of seven of people with Crohn’s disease, and another analysis of Crohn’s patients found D. hansenii present but only in sites of injury and inflammation. 

“If you look at stool samples from healthy people, this fungus is highly abundant,” Jain said. “It goes into your body and comes out again. But people with Crohn’s disease have a defect in the intestinal barrier that enables the fungus to get into the tissue and survive there. And then it makes itself at home in ulcers and sites of inflammation and prevents those areas from healing.”

Their results suggest that elimination of the fungus could allow wounds to heal normally again, and minimise flare-ups. In mouse studies, amphotericin B eliminated the fungus but it is of limited use in people since it can only be administered intravenously, therefore an oral antifungal is being researched.

“Crohn’s disease is fundamentally an inflammatory disease, so even if we figured out how to improve wound healing, we wouldn’t be curing the disease,” Jain said. “But in people with Crohn’s, impaired wound healing causes a lot of suffering. If we can show that depleting this fungus in people’s bodies—either by dietary changes or with antifungal medications—could improve wound healing, then it may affect the quality of life in ways that we’ve not been able to do with more traditional approaches.”

Source: Medical Xpress

Journal information: U. Jain et al., “Debaryomyces is enriched in Crohn’s disease intestinal tissue and impairs healing in mice,” Science (2021). science.sciencemag.org/cgi/doi … 1126/science.abd0919

Categories : UncategorizedTags :

Inflammatory Foods Raise Cardiovascular Risk

On By ModernMedia

A pair of studies have examined the effect that the dietary inflammatory index has on cardiovascular health, and found that inflammatory foods increase cardiovascular risk.

It is known that inflammatory biomarkers such as interleukins, chemokines and adhesion molecules are associated with atherosclerosis, and proinflammatory foods such as red meats are also associated with cardiovascular risk. The study examined 210 000 participants over 32 years, who filled out a dietary survey every four years, and controlled for variables such as overweight.

“Using an empirically-developed, food-based dietary index to evaluate levels of inflammation associated with dietary intake, we found that dietary patterns with higher inflammatory potential were associated with an increased rate of cardiovascular disease,” said Jun Li, MD, Ph.D., lead author of the study and research scientist in the department of nutrition at Harvard T.H. Chan School of Public Health. “Our study is among the first to link a food-based dietary inflammatory index with long-term risk of cardiovascular disease.”

The other study looked at the beneficial effects of walnuts, which have a strong anti-inflammatory effect. Participants who were assigned to eat 30-60gm of walnuts a day showed significantly reduced inflammation in 6 of 10 biomarkers used.

“The anti-inflammatory effect of long-term consumption of walnuts demonstrated in this study provides novel mechanistic insight for the benefit of walnut consumption on heart disease risk beyond that of cholesterol lowering,” said Montserrant Cofán, Ph.D., lead author of the study and a researcher at the August Pi i Sunyer Biomedical Research Institute in Barcelona, Spain.

Source: Medical Xpress

Categories : UncategorizedTags :

Brain Swelling Has an Unexpected Protective Effect

On By ModernMedia

Animal studies have shown that swelling in the brain can protect it in the longer term. Dangerous brain activity can take place after a brain injury (such as from blunt trauma), where neural network activity can surge to dangerous levels, resulting in seizures and tissue injury for months or years after the original injury. Swelling may reduce this long-term effect, an unexpected protective benefit.

At the University of Utah, Punam Sawant-Pokam, PhD, and KC Brennan, MD, investigated the effects of cerebral injury and swelling. They examined the brains of mice subjected to injury with a range of advanced tools for brain recording and electrical activity, 

When observations were made 48 hours after injury, when maximum swelling usually appears, untreated mice brains showed swollen neurons but their neuronal activity had surprisingly dropped. Mice that were given drugs to reduce swelling showed that the neurons continued to show over-activity.

“This data prompts a pretty big reconsideration of how we view edema after brain injury,” Brennan said. “When oedema is about to cause death, it is the number one priority. We’re not saying this is not true. But we’re opening up more nuance to the phenomenon in a way that might allow us to eventually get to more specific treatments and better outcomes.

“It’s very exciting to know that neuronal oedema is not only reducing cellular excitability, it’s also protecting the brain from dangerous network events,” Sawant-Pokam said.

The findings suggest that patients could benefit from more targeted approaches to dealing with cerebral oedema.

Source: Medical Xpress