Tag: neuroinflammation

Memory is Impaired in Aged Rats After 3 Days of High-fat Diet

Some fast food offerings, such as cheeseburgers, contain more than 60% of calories from fat. Photo by Jonathan Borba

Just a few days of eating a diet high in saturated fat could be enough to cause memory problems and related brain inflammation in older adults, a new study in rats suggests. 

In the study, published in Immunity & Aging, researchers fed separate groups of young and old rats the high-fat diet for three days or for three months to compare how quickly changes happen in the brain versus the rest of the body when eating an unhealthy diet. 

As expected based on previous diabetes and obesity research, eating fatty foods for three months led to metabolic problems, gut inflammation and dramatic shifts in gut bacteria in all rats compared to those that ate normal chow, while just three days of high fat caused no major metabolic or gut changes.

When it came to changes in the brain, however, researchers found that only older rats – whether they were on the high-fat diet for three months or only three days – performed poorly on memory tests and showed negative inflammatory changes in the brain. 

The results dispel the idea that diet-related inflammation in the aging brain is driven by obesity, said senior study author Ruth Barrientos, an investigator in the Institute for Behavioral Medicine Research at The Ohio State University. Most research on the effects of fatty and processed foods on the brain has focused on obesity, yet the impact of unhealthy eating, independent of obesity, remains largely unexplored. 

“Unhealthy diets and obesity are linked, but they are not inseparable. We’re really looking for the effects of the diet directly on the brain. And we showed that within three days, long before obesity sets in, tremendous neuroinflammatory shifts are occurring,” said Barrientos, also an associate professor of psychiatry and behavioural health and neuroscience in Ohio State’s College of Medicine.  

“Changes in the body in all animals are happening more slowly and aren’t actually necessary to cause the memory impairments and changes in the brain. We never would have known that brain inflammation is the primary cause of high-fat diet-induced memory impairments without comparing the two timelines.” 

Years of research in Barrientos’ lab has suggested that aging brings on long-term “priming” of the brain’s inflammatory profile coupled with a loss of brain-cell reserve to bounce back, and that an unhealthy diet can make matters worse for the brain in older adults. 

Fat constitutes 60% of calories in the high-fat diet used in the study, which could equate to a range of common fast-food options: For example, nutrition data shows that fat makes up about 60% of calories in a McDonald’s double smoky BLT quarter pounder with cheese or a Burger King double whopper with cheese

After the animals were on high-fat diets for three days or three months, researchers ran tests assessing two types of memory problems common in older people with dementia that are based in separate regions of the brain: contextual memory mediated by the hippocampus (the primary memory center of the brain), and cued-fear memory that originates in the amygdala (the fear and danger center of the brain). 

Compared to control animals eating chow and young rats on the high-fat diet, aged rats showed behaviors indicating both types of memory were impaired after only three days of fatty food – and the behaviors persisted as they continued on the high-fat diet for three months. 

Researchers also saw changes in levels of a range of proteins called cytokines in the brains of aged rats after three days of fatty food, which signaled a dysregulated inflammatory response. Three months after being on the high-fat diet, some of the cytokine levels had shifted but remained dysregulated, and the cognitive problems persisted in behavior tests. 

“A departure from baseline inflammatory markers is a negative response and has been shown to impair learning and memory functions,” Barrientos said. 

Compared to rats eating normal chow, young and old animals gained more weight and showed signs of metabolic dysfunction – poor insulin and blood sugar control, inflammatory proteins in fat (adipose) tissue, and gut microbiome alterations – after three months on the high-fat diet. Young rats’ memory and behavior and brain tissue remained unaffected by the fatty food. 

“These diets lead to obesity-related changes in both young and old animals, yet young animals appear more resilient to the high-fat diet’s effects on memory. We think it is likely due to their ability to activate compensatory anti-inflammatory responses, which the aged animals lack,” Barrientos said. 

“Also, with glucose, insulin and adipose inflammation all increased in both young and old animals, there’s no way to distinguish what is causing memory impairment in only old animals if you look only at what’s happening in the body. It’s what is happening in the brain that’s important for the memory response.” 

Source: Ohio State University

Review Re-evaluates Biomarker for Imaging Neuroinflammation

Photo by Mart Production on Pexels

Neuroinflammation can lead to serious neurological or psychiatric diseases, for which there is presently one biomarker available for medical imaging to visualise cerebral inflammation. Trouble is, it has been unclear how to interpret this biomarker. Researchers have now found that a large quantity of this protein indicates a large quantity of inflammatory cells, but its presence is not a sign of their overactivation. These results, published in Nature Communications, pave the way for optimal observation of neuroinflammatory processes with other potential biomarkers, and a re-evaluation of prior research.

In the brain, microglial cells play an important role in inflammation and its potential overactivation. They can be ”activated” when dysfunction occurs, phagocytise pathological cells or proteins and even produce protective substances. Currently, in medical imaging, only one marker can be used to locate and measure microglia non-invasively and in vivo: the TSPO protein, which is present in these cells. This protein can be observed by Positron Emission Tomography (PET), a common imaging technique.

A TSPO of insight

”Hundreds of studies have used PET scans of this protein to explore and quantify microglia. However, no study has succeeded in precisely interpreting the significance of its quantity in the context of an inflammatory reaction,” explains Stergios Tsartsalis, senior clinical associate in the Department of Psychiatry at the UNIGE Faculty of Medicine. Together with other researchers, Stergios Tsartsalis sought to determine if a large quantity of TSPO correspond to a large quantity of inflammatory cells, and whether it is a sign of their overactivation.

The international research team worked on the brains of mouse models of Alzheimer’s disease, amyotrophic lateral sclerosis and multiple sclerosis, and on post-mortem brain samples from patients affected by the same diseases. ”We discovered that a high density of TSPO protein is indeed an indicator of a high density of microglia. On the other hand, the observation of TSPO does not allow us to say whether or not the inflammatory cells are overactivated,” explains the UNIGE researcher, co-first author of the study.

Re-reading the past, optimising the future

This discovery highlights the value of medical imaging of TSPO: it makes it possible to identify cases where the neuroinflammatory disease is linked to a deregulation in the number of glial cells. In addition, the scientists have identified two markers of the state of microglia activation in humans – the LCP2 and TFEC proteins – setting the stage for new medical imaging approaches.

”These results represent a further step towards understanding the role of microglia in neuroinflammation. They will help to optimise the focus of future studies and also to review the conclusions of previous research,” enthuses Stergios Tsartsalis.

Source: Université de Genève

Hyperbaric Therapy Reduces Neuroinflammation in Autism

Depiction of a human brain
Image by Fakurian Design on Unsplash

A new study at Tel Aviv University showed significant improvements in social skills and the condition of the autistic brain through hyperbaric therapy. The study which is reported in the journal International Journal of Molecular Sciences, was conducted on lab models of autism.

Hyperbaric medicine, where patients sit in special high-pressure chambers while breathing pure oxygen, is considered safe and, besides treating decompression sickness in divers, is already in use for other conditions. The use of hyperbaric medicine to treat autism is contentious, with many holding that it is based on pseudoscience. In recent years, scientific evidence has been accumulating that unique protocols of hyperbaric treatments improve the supply of blood and oxygen to the brain, thereby improving brain function.

Changes observed in the brain included a reduction in neuroinflammation, which is known to be associated with autism. A significant improvement was also found in the social functioning of the animal models treated in the pressure chamber. The study’s success has many implications regarding the applicability and understanding of treating autism using pressure chamber therapy.

The breakthrough was led by doctoral student Inbar Fischer, from the laboratory of Dr Boaz Barak of Tel Aviv University.

Improved brain function

“The medical causes of autism are numerous and varied, and ultimately create the diverse autistic spectrum with which we are familiar,” explains Dr Barak. “About 20% of autistic cases today are explained by genetic causes, that is, those involving genetic defects, but not necessarily ones that are inherited from the parents. Despite the variety of sources of autism, the entire spectrum of behavioural problems associated with it are still included under the single broad heading of ‘autism,’ and the treatments and medications offered do not necessarily correspond directly to the reason why the autism developed.”

In the preliminary phase of the study, a girl carrying the mutation in the SHANK3 gene, which is known to lead to autism, received treatments in the pressure chamber, conducted by Prof Shai Efrati. After the treatments, it was evident that the girl’s social abilities and brain function had improved considerably.

In the next stage, and in order to comprehend the success of the treatment more deeply, the team of researchers at Dr Barak’s laboratory sought to understand what being in a pressurised chamber does to the brain. To this end, the researchers used lab models carrying the same genetic mutation in the SHANK3 gene as that carried by the girl who had been treated. The experiment comprised a protocol of 40 one-hour treatments in a pressure chamber over several weeks.

“We discovered that treatment in the oxygen-enriched pressure chamber reduces inflammation in the brain and leads to an increase in the expression of substances responsible for improving blood and oxygen supply to the brain, and therefore brain function,” explains Dr Barak. “In addition, we saw a decrease in the number of microglial cells, immune system cells that indicate inflammation, which is associated with autism.”

Increased social interest

“Beyond the neurological findings we discovered, what interested us more than anything was to see whether these improvements in the brain also led to an improvement in social behaviour, which is known to be impaired in autistic individuals,” adds Dr Barak. “To our surprise, the findings showed a significant improvement in the social behaviour of the animal models of autism that underwent treatment in the pressure chamber compared to those in the control group, who were exposed to air at normal pressure, and without oxygen enrichment. The animal models that underwent treatment displayed increased social interest, preferring to spend more time in the company of new animals to which they were exposed in comparison to the animal models from the control group.”

Inbar Fischer concludes, “the mutation in the animal models is identical to the mutation that exists in humans. Therefore, our research is likely to have clinical implications for improving the pathological condition of autism resulting from this genetic mutation, and likely also of autism stemming from other causes. Because the pressure chamber treatment is non-intrusive and has been found to be safe, our findings are encouraging and demonstrate that this treatment may improve these behavioral and neurological aspects in humans as well, in addition to offering a scientific explanation of how they occur in the brain.”

Source: Tel Aviv University