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Nerve damage from neurodegenerative conditions, traumatic injuries, and certain eye conditions leads to disability and death for millions of people in the United States. Currently, doctors consider such damage irreversible.

However, researchers at The Ohio State University Wexner Medical Center have discovered a new type of human immune cell that appears to prevent and reverse nerve damage in the optic nerve and spinal cord.

This finding could allow researchers to create more advanced neurodegenerative immunotherapies.

These therapies might offer fresh hope to people with currently incurable neurological conditions, including Alzheimer’s diseasemultiple sclerosis, stroke, and Parkinson’s disease. They might also help treat central nervous system (CNS) damage from injury or infection.

“I treat patients who have permanent neurological deficits, and they have to deal with debilitating symptoms every day, “says Dr. Benjamin Segal, professor and chair of the Department of Neurology at The Ohio State College of Medicine and co-director of the Ohio State Wexner Medical Center’s Neurological Institute.

“So the idea of being able to restore neurological function and take that burden away from my patients is really amazing.”

Funded by the National Eye Institute (NEI), the National Institutes of Health (NIH), the Wings of Life Foundation (C.Y.), and the Dr. Miriam and Sheldon G. Adelson Research Foundation, the study appears in the journal Nature Immunology.

The emerging field of immunotherapy

Immunotherapy therapies alter the immune response by stimulating it or using the body’s own immune cells to treat disease. Over the past few decades, scientists have begun developing them to tackle a wide range of medical conditions.

Doctors already use immunotherapies to treat certain types of cancer. They help the immune system to recognize and destroy cancer cells.

Other researchers are investigating whether immunotherapy could help prevent or treat neurological disease.

Researchers have been extensively testing immunotherapies that increase the clearance rate of certain proteins whose accumulation has links with neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and dementia with Lewy bodies.

Scientists have already created T-cell mediated immunotherapy approaches that target proteins linked with these neurological diseases, such as amyloid-beta, tau, and alpha-synuclein proteins.

Immunotherapy may also present opportunities to prevent and treat nerve damage by activating alternative immune pathways in response to CNS damage.

2014 study found that anti-inflammatory or immunoregulating (M2) macrophages are critical for remyelination, which is a form of nerve repair.

The study

The researchers examined immune cells in fluids and spinal cord tissues collected from mice with optic and spinal nerve damage.

Within these fluids and tissues, the team found a unique type of granulocyte. Granulocytes are a category of white blood cells. Neutrophils are the most common kind of granulocytes.

Neutrophils are scavengers that help destroy pathogens or other unwanted particles in the body. The new type of granulocyte that the scientists identified behaved like an immature neutrophil.

This newly discovered granulocyte helped protect neural cells and tissues from damage in the mice. It also encouraged nerve cell regeneration by secreting a mix of beneficial growth compounds. The team also found a human cell line with similar neuroprotective properties.

“This type of cell actually secretes growth factors to rescue dying nerve cells. It can also stimulate the surviving nerve cells to grow new fibers once they’re severed or damaged in the [CNS], which is really unprecedented,” says Dr. Segal. “This can potentially lead to therapeutic breakthroughs for a wide range of conditions by repairing these nerve pathways.”

However, researchers have a long way to go before doctors can use immune cells, such as this newly discovered granulocyte, to treat humans.

The team’s first major hurdle will be figuring out how to harness the power of this new immune cell and enhance its natural healing effects by growing it in a laboratory setting. Next, they’ll have to prove their newly proposed therapy is both effective and safe in humans.

In the future, the team hopes that doctors can inject these novel cells into people with chronic cognitive deficits to slow down or halt degenerative decline.

Dr. Segal concludes that they have got a lot of work left to do to make their laboratory findings relevant in a clinical setting, but says he is optimistic about the road ahead:

“There’s so much that we’re learning at the bench that has yet to be translated to the clinic, but I think there’s huge potential for the future.”

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Researchers have discovered an imbalance in the amounts of fatty molecules called lipids inside the brain cells of people with Parkinson’s disease. A buildup of lipids in nerve cells may cause inflammation.

Parkinson’s disease is a movement disorder that gets progressively worse over time.

The death of dopamine-producing nerve cells in the substantia nigra region of the brain causes the illness. Dopamine is a neurotransmitter that plays several vital roles, including regulating motivation, reward, and movement.

However, the exact train of events leading to the death of dopamine-producing cells remains unclear.

Researchers have focused much of their attention on a misfolded form of a protein called alpha-synuclein as the trigger for Parkinson’s. Studies have found toxic clumps or aggregates of the misfolded protein in the brains of people with the disease.

However, an alternative theory proposes that lipid dysregulation and inflammation play a more important role, similar to the part played by fatty plaques and inflammation in the walls of arteries in cardiovascular disease.

Researchers at the Neuroregeneration Institute at McLean Hospital in Belmont, MA, have now discovered an accumulation of lipids in dopamine-producing neurons in the postmortem brains of people who had Parkinson’s.

The excess amounts of lipid in these nerve cells correlate with changes in lipid levels in neighboring cells called microglia and astrocytes. They also found evidence of inflammation.

When the researchers simulated a breakdown of lipid metabolism in an animal model of the disease, they saw remarkably similar changes.

“These results support our lipid-inflammation hypothesis in the causation of Parkinson’s disease initiation and progression,” says senior author Dr. Ole Isacson, who is the founding director of the Neuroregeneration Institute and a professor of neurology at Harvard Medical School in Boston, MA.

“[The results] may help us discover and develop new therapies by leaving behind conventional thinking about [Parkinson’s disease] pathology, which to some extent has been limited to neurons and protein aggregates,” he adds.

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

Postmortem tissue samples

The scientists compared postmortem brain tissue from 26 individuals with Parkinson’s with 23 age-matched controls without the disease.

They used fluorescent lipid-binding molecules to determine lipid levels in different brain cells in the substantia nigra.

In brain tissue from people with Parkinson’s, there was an accumulation of lipids inside dopamine nerve cells, which was matched by a deficiency of lipids within astrocytes in the same samples.

Astrocytes are star-shaped cells that support nerve cells, both structurally and through the exchange of nutrients and their byproducts.

In their paper, the researchers note that nerve cells have a limited capacity to use lipids for energy, with excess amounts being transported to neighboring astrocytes to avoid the buildup of toxic byproducts.

This did not seem to be happening correctly in the brains of individuals with Parkinson’s.

Compared with healthy brain tissue, the scientists also found excess amounts of lipid inside microglia, which are the brain’s immune cells.

They also discovered high levels of a signaling molecule called GPNMB. Scientists know that astrocytes produce this molecule in response to inflammation caused by the build up of lipids.

The scientists found that levels of this molecule correlated with the total amount of lipid in the brain tissue of individuals with Parkinson’s.

Mouse model of Parkinson’s

Finally, the scientists investigated whether they could reproduce these effects in mice by disrupting lipid metabolism in the animals’ brains.

One of the most significant genetic risk factors for Parkinson’s is a mutation in a gene for an enzyme that breaks down lipids.

When the researchers injected the mice with a chemical that inhibits this enzyme, they found the same pattern of changes in lipid distribution that they had seen in brain tissue from people with Parkinson’s.

Previous research has found telltale deposits of alpha-synuclein in mice injected with this enzyme inhibitor.

In their paper, the scientists conclude:

“Therapies and agents that reverse the pathological cell-type-specific lipid distribution in the [substantia nigra of people with Parkinson’s] could serve to prevent and reduce the progression of [Parkinson’s disease] and related neurodegenerative disorders.”

However, researchers need to carry out much more research to confirm the findings and translate them into effective and safe treatments.

Scientists have found associations between fungi living in the gut and mild cognitive impairment, which can lead to Alzheimer’s disease. They suggest that a ketogenic diet could help prevent the disease by creating a more healthful balance of microorganisms in the gut.

Alzheimer’s Association report that 15–20% of people over 65 experience mild cognitive impairment (MCI), which involves a decline in memory and the ability to think clearly.

Doctors do not consider MCI to be a form of dementia because people who have it are able to function relatively well and live independently. However, MCI is associated with an increased risk of Alzheimer’s disease or another form of dementia later in life.

Developing preventive strategies that can be initiated early is therefore a priority. But despite decades of research, no therapies have been shown to reverse or prevent the brain changes seen in Alzheimer’s.

One potential strategy that scientists have begun to explore involves modifying the diet to influence the microbial communities in the gut.

There is an intimate relationship between the gut microbiome and the central nervous system, with recent research suggesting associations between particular bacterial communities and neurological disorders, including MCI, dementia, and Alzheimer’s.

In one recent study, scientists at the Wake Forest School of Medicine, in Winston-Salem, NC, found a distinctive gut bacterial “signature” in people with MCI.

They also discovered that a diet called the modified Mediterranean-style ketogenic diet altered bacterial communities in the guts of volunteers and reduced biomarkers of Alzheimer’s disease in the cerebrospinal fluid of those with MCI.

This diet contains a limited number of carbohydrates and increased amounts of fats. These are primarily mono- and polyunsaturated fats that come from olive oil and fish.

ketogenic, or “keto”, diet contains very few carbohydrates, which the body uses as fuel. When short on carbs, the body starts to break down its fat reserves to produce molecules called ketones, as an alternative source of energy.

The same group of researchers now reports similar associations between the communities of fungi in the gut — collectively called the mycobiome — the person’s diet, and their risk of MCI.

They report their findings in the latest issue of the journal EBioMedicine.

Fungi and brain health

“Although we do not fully understand how these fungi contribute to Alzheimer’s disease, this is the first study of its kind to reveal their role in our mental health, which we hope will ignite thinking in the scientific community to develop better understanding of them in relation to Alzheimer’s disease,” says principal investigator Hariom Yadav, Ph.D., an assistant professor of molecular medicine at Wake Forest.

“It also indicates that dietary habits such as eating a ketogenic diet can reduce harmful fungi in the gut, which might help in reducing Alzheimer’s disease processes in the brain,” he explains.

The researchers randomly assigned 17 older adults to eat either a Mediterranean-style ketogenic diet (MMKD) for 6 weeks or the American Heart Association diet, which is relatively low in fat and high in carbohydrates.

Eleven of the participants had MCI and six had no cognitive issues. Their average age was 65 years.

The team provided each participant assigned to the MMKD with 2 liters of extra virgin olive oil and encouraged them to eat fish, lean meats, and nutrient-rich foods.

After a 6-week “washout” period during which the participants maintained their regular diets, they switched to their study-assigned diets for 6 weeks.

The scientists monitored changes in the participants’ mycobiomes by analyzing fecal samples and changes in Alzheimer’s biomarkers by assessing samples of cerebrospinal fluid.

Fungal signature and diet

At the start of the study, the mycobiomes of participants with MCI had a distinctive signature, containing more of certain types of fungi and fewer of others, compared with those of the other participants.

As expected, MCI was associated with a high-risk profile of Alzheimer’s biomarkers in cerebrospinal fluid. In keeping with previous findings, following an MMKD appeared to improve this risk profile.

Interestingly, individuals with MCI initially had less fungal diversity in their guts, compared with the healthy participants, but eating an MMKD seemed to restore the diversity.

The researchers note that changes in the populations of gut bacteria of individuals with MCI who ate an MMKD — which they had reported in their previous study — may have had knock-on effects on the fungi.

Some species of bacteria produce substances known to suppress the growth of certain fungi. The authors report that this may explain why eating an MMKD suppressed a genus of fungi called Candida in the guts of participants with MCI.

Candida has been implicated in a range of inflammatory diseases of the gut, including Crohn’s disease and ulcerative colitis.

Inflammation is now believed to play an important role in Alzheimer’s disease, as well. By suppressing Candida and reducing inflammation, say the researchers, eating an MMKD may help reduce the risk of Alzheimer’s.

Study limitations

The authors acknowledge that their study had some key limitations. First, while the researchers advised people to eat certain diets, they did not monitor the participants for this.

It was also a pilot study with a small sample size, making it impossible to account for other variables that might affect Alzheimer’s risk and the population of the gut’s microorganisms, such as lifestyle, gender, and ethnicity.

Moreover, the unique signature of gut fungi and bacteria found in individuals with MCI may be a result of the health issue, rather than one of its causes.

Finally, the changes in the mycobiome observed in the participants assigned the keto diet may have been transient, resulting from fungi in the food.