Raising eyebrows on neuroinflammation: Study finds novel role for 'skin plumping' molecule

Neuroscientists identify surprising brain action of cartilage component hyaluronic acid

July 11, 2019

Science Daily/Florida Atlantic University

Scientists have discovered a novel mechanism and role in the brain for hyaluronic acid -- a clear, gooey substance popularized by cosmetic and skin care products. Hyaluronic acid may be the key in how an immune signal moves from the blood stream to the brain, activating the brain's resident immune cells, the microglia. Findings from this study have important implications for better treatments for stroke, neurodegenerative diseases, as well as head injuries.

This clear, gooey substance, which is naturally produced by the human body, has been popularized by cosmetic and skin care products that promote healthier, plumper and more supple skin. Also recognized for its abilities to speed up wound healing, reduce joint pain from osteoarthritis, and relieve dry eye and discomfort, a neuroscientist at Florida Atlantic University's Brain Institute (I-BRAIN) and Schmidt College of Medicine, has discovered a novel mechanism and role in the brain for hyaluronic acid.

In a study published in the journal Brain, Behavior and Immunity, Ning Quan, Ph.D., lead author, a professor of biomedical science in FAU's Schmidt College of Medicine and a member of I-BRAIN, and collaborators, have discovered that hyaluronic acid may be the key in how an immune signal moves from the blood stream to the brain, activating the brain's resident immune cells, the microglia.

This unsuspected molecule may be the main signal passed between these cells, and this new discovery could lead to novel opportunities to shut down brain inflammatory responses. Findings from this study have important implications for better treatments for stroke, neurodegenerative diseases, as well as head injuries.

"We normally think of hyaluronic acid with respect to cartilage formation and also for its role in many processes including cancer progression and metastasis," said Quan. "However, what we have uncovered in our study is a completely unique role for this molecule. We have been able to document a connection between the blood cells and the brain cells, showing that the activating signal passed between these cells is hyaluronic acid."

Quan and collaborators from the Sichuan University, The Ohio State University, and the University of Illinois Urbana-Champaign, demonstrate that inflammation in the central nervous system is oftentimes quenched or restricted, as neurons are extremely vulnerable to inflammation-caused damages. However, this inflammation can be aberrantly amplified through endothelial cell-microglia crosstalk when the brain constantly receives inflammatory signals. Quan's work identified hyaluronic acid as the key signal released by endothelial cells to stimulate microglia and promote oxidative damage.

"To prevent the inflammation from being intensified in the brain, you have to stop the communication between the two cell types," said Xiaoyu Liu, Ph.D., another corresponding author of the study in FAU's Schmidt College of Medicine and I-BRAIN. "We found ascorbyl palmitate, also known as 'Vitamin C Ester,' to be quite effective in inhibiting microglia and reducing the production of inflammatory hyaluronic acid."

In the past, Vitamin C Ester has been widely used as a source of vitamin C and an antioxidant food additive. Now, this latest discovery suggests a novel function of Vitamin C Ester: treating central nervous system inflammation.

"As the newest addition to our Department of Biomedical Science, Dr. Quan's work already is making an important impact on our mission to advance understanding of human health and disease," said Janet Robishaw, Ph.D., senior associate dean for research and chair of the Department of Biomedical Science in FAU's Schmidt College of Medicine. "Long known as a popular skin and joint supplement, this discovery identifies a novel role for hyaluronic acid to potentially treat conditions caused by inflammation in the central nervous system."

Inflammation can occur in the central nervous system as a result of head trauma or stroke, or as part of a systemic immune response. Inflammation within the central nervous system has been associated with chronic neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and multiple sclerosis.

"Neurological disorders such as Parkinson's disease and Alzheimer's disease impact all races, genders, and geographical backgrounds," said Randy Blakely, Ph.D., executive director of FAU's I-BRAIN. "Findings from this study may thus have global implications for how we treat neurodegeneration arising from traumatic brain injuries and brain changes associated with aging and dementia. This exceptional research by Dr. Quan and his colleagues is a testament to the cutting-edge work that is being conducted by our Brain Institute members and the research faculty in FAU's Schmidt College of Medicine."

https://www.sciencedaily.com/releases/2019/07/190711141439.htm

Bacteria found in Alzheimer's brains

Brains from patients with Alzheimer's disease show changes in bacterial populations compared with healthy brains

July 17, 2017

Science Daily/Frontiers

Researchers have used DNA sequencing to examine bacteria in post-mortem brains from patients with Alzheimer's disease. Their findings suggest increased bacterial populations and different proportions of specific bacteria in Alzheimer's, compared with healthy brains. The findings may support evidence that bacterial infection and inflammation in the brain could contribute to Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disease that results in cognitive decline, and eventually death. In the brain, the disease causes neurons to die and break down, and involves high levels of a peptide called amyloid and aggregations of a protein called tau. However, scientists are coming to appreciate that inflammation may also play a role.

"Alzheimer's brains usually contain evidence of neuroinflammation, and researchers increasingly think that this could be a possible driver of the disease, by causing neurons in the brain to degenerate," says David Emery, a researcher from the University of Bristol, and an author on the study, which was recently published in Frontiers in Aging Neuroscience.

So, what's causing this inflammation? Some genetic risk-factors for Alzheimer's disease can have effects on the inflammatory response, but infection may also play a role. "Neuroinflammation in the brain may be a reaction to the presence of bacteria," says Emery. The brain is normally sealed behind specialized blood vessels that make it very difficult for things like bacteria in the blood to enter. However, at least one of the genetic risk-factors for Alzheimer's disease may cause these blood vessels to lose some of their integrity, which could allow bacteria to enter and colonize the brain.

The research team set out to discover if there were any differences in the types of bacteria present in brains from Alzheimer's disease patients and healthy brains. "Previous studies looking at bacteria in the Alzheimer's brain have primarily investigated specific bacterial species," explains Shelley Allen, another researcher involved in the study. "We wanted to use an unbiased method to obtain the fullest overview possible of the entire bacterial population in the Alzheimer's brain, and compare these results with those from a healthy aged brain."

The researchers analyzed eight Alzheimer's and six healthy brain samples from a brain bank, where people donate their brains after death for medical research. They used a technique called next generation sequencing (NGS) to detect specific bacterial genes. "NGS technology allows millions of these DNA molecules to be sequenced at the same time, providing an unbiased overview of a complex bacterial population," explains Allen.

They found that the Alzheimer's brains contained different proportions of specific bacteria compared with the healthy brains. "Comparing the bacterial populations showed at least a tenfold higher ratio overall of Actinobacteria (mostly P. acnes) to Proteobacteria in the Alzheimer's brain compared with the healthy brain," says Emery.

However, the researchers were surprised to find that there also appeared to be more bacteria in the Alzheimer's brains. "Unexpectedly, Alzheimer's brains gave on average an apparent 7-fold increase in bacterial sequences above that seen in the healthy brain," says Allen. "The healthy brains yielded only low levels of bacterial sequences, consistent with either a background signal or normal levels present in the blood stream in brain tissue."

The team caution that the NGS method does not directly indicate actual bacterial numbers, and further work will be required to confirm that bacteria play an active role in Alzheimer's disease. "We need quantitative studies on the bacterial presence in the brain," says Allen. "Larger numbers of brain samples are required, and future studies should also investigate if bacteria are involved in other neurodegenerative diseases involving neuroinflammation."

https://www.sciencedaily.com/releases/2017/07/170717100425.htm