Researchers identify 10 pesticides toxic to neurons involved in Parkinson’s

Photo Credit: Rosyid Arifin

Researchers at UCLA Health and Harvard have identified 10 pesticides that significantly damaged neurons implicated in the development of Parkinson’s disease, providing new clues about environmental toxins’ role in the disease.

While environmental factors such as pesticide exposure have long been linked to Parkinson’s, it has been harder to pinpoint which pesticides may raise risk for the neurodegenerative disorder. Just in California, the nation’s largest agricultural producer and exporter, there are nearly 14,000 pesticide products with over 1,000 active ingredients registered for use.

Through a novel pairing of epidemiology and toxicity screening that leveraged California’s extensive pesticide use database, UCLA and Harvard researchers were able to identify 10 pesticides that were directly toxic to dopaminergic neurons. The neurons play a key role in voluntary movement, and the death of these neurons is a hallmark of Parkinson’s.

Further, the researchers found that co-exposure of pesticides that are typically used in combinations in cotton farming were more toxic than any single pesticide in that group.

New study explains how a common virus can cause multiple sclerosis

Olivia Thomas and Mattias Bronge
Photo Credit: Erik Holmgren

Researchers at Karolinska Institutet have found further evidence for how the Epstein-Barr virus can trigger multiple sclerosis or drive disease progression. A study published in Science Advances shows that some individuals have antibodies against the virus that mistakenly attacks a protein in the brain and spinal cord.

The Epstein-Barr virus (EBV) infects most people early in life and then remains in the body, usually without causing symptoms. The link between EBV and the neurological disease multiple sclerosis (MS) was discovered many years ago and has puzzled researchers ever since. Increasing evidence, including two papers published in Science and Nature last year, suggests that EBV infection precedes MS and that antibodies against the virus may be involved. However, the molecular mechanisms seem to vary between patients and remain largely unknown.

“MS is an incredibly complex disease, but our study provides an important piece in the puzzle and could explain why some people develop the disease,” says Olivia Thomas, postdoctoral researcher at the Department of Clinical Neuroscience, Karolinska Institutet and shared first author of the paper. “We have discovered that certain antibodies against the Epstein-Barr virus, which would normally fight the infection, can mistakenly target the brain and spinal cord and cause damage.”

UC Irvine research team identifies glycosylation enzyme critical in brain formation

Lisa Flanagan, professor of neurology
Photo Credit: Courtesy of University of California, Irvine

The MGAT5 glycosylation enzyme plays a crucial role in brain development, according to a study by University of California, Irvine researchers, a discovery that may contribute to new therapeutic purposes for neural stem cells.

Neurons, astrocytes and oligodendrocytes are the final mature cells of the brain and spinal cord formed by neural stem cells. Each has distinct and key functions. Neurons transmit signals, astrocytes help modify those signals, and oligodendrocytes keep the signals from degrading. When any cells make proteins or fats that end up on the cell surface, they often add small sugar molecules. The team tested whether this internal process – called glycosylation – affects how neural stem cells form mature brain cells.

The study, published in the journal Stem Cell Reports, found that during glycosylation, the MGAT5 enzyme significantly regulates the formation of neurons and astrocytes from neural stem cells. Neural stem cells that don’t have MGAT5 make more neurons and fewer astrocytes during the very early stages of brain development, altering its structure. These changes may contribute to later aberrant behavior patterns, including abnormal social interactions and repetitive actions.

Insight into brain’s waste clearing system may shed light on brain diseases

The image shows a microscopic image revealing the enhanced glymphatic transport of an intranasally delivered tracer (red), achieved using ultrasound combined with microbubbles.
Image Credit: Chen lab

Like the lymphatic system in the body, the glymphatic system in the brain clears metabolic waste and distributes nutrients and other important compounds. Impairments in this system may contribute to brain diseases, such as neurodegenerative diseases and stroke.

A team of researchers in the McKelvey School of Engineering at Washington University in St. Louis has found a noninvasive and nonpharmaceutical method to influence glymphatic transport using focused ultrasound, opening the opportunity to use the method to further study brain diseases and brain function. Results of the work are published in Proceedings of the National Academy of Sciences May 15, 2023.

Hong Chen, associate professor of biomedical engineering in McKelvey Engineering and of neurological surgery in the School of Medicine, and her team, including Dezhuang (Summer) Ye, a postdoctoral research associate, and Si (Stacie) Chen, a former postdoctoral research associate, found the first direct evidence that focused ultrasound, combined with circulating microbubbles — a technique they call FUSMB — could mechanically enhance glymphatic transport in the mouse brain. 

Focused ultrasound can penetrate the scalp and skull to reach the brain and precisely target a defined region within the brain. In previous work, Chen’s team found that microbubbles injected into the bloodstream amplify the effects of the ultrasound waves on the blood vessels and generate a pumping effect, which helps with the accumulation of intranasally-delivered agents in the brain, such as drugs or gene therapy treatments.

Brain research with organoids

Section of an electroporated brain organoid of a common marmoset. Green: electroporated cells that glow green due to the green fluorescent protein; magenta: neurons; gray: nuclei.
Photo Credit: Lidiia Tynianskaia

Scientists at the German Primate Center develop effective method to genetically modify brain organoids

Primates are among the most intelligent creatures with distinct cognitive abilities. Their brains are relatively large in relation to their body stature and have a complex structure. However, how the brain has developed over the course of evolution and which genes are responsible for the high cognitive abilities is still largely unclear. The better our understanding of the role of genes in brain development, the more likely it will be that we will be able to develop treatments for serious brain diseases. 

Researchers are approaching these questions by knocking out or activating individual genes and thus drawing conclusions about their role in brain development. To avoid animal experiments as far as possible, brain organoids are used as an alternative. These three-dimensional cell structures, which are only a few millimeters in size, reflect different stages of brain development and can be genetically modified. However, such modifications are usually very complex, lengthy and costly. Researchers at the German Primate Center (DPZ) – Leibniz Institute for Primate Research in Göttingen have now succeeded in genetically manipulating brain organoids quickly and effectively. 

Combined delivery of engineered virus with immunotherapy is safe and improves outcomes in subset of patients with glioblastoma

From left to right: Frederick Lang, M.D., Juan Fueyo, M.D., and Candelaria Gomez-Manzano, M.D.
Image Credit: Courtesy of MD Anderson Cancer Center

Intratumoral delivery of an engineered oncolytic virus (DNX-2401) targeting glioblastoma (GBM) cells combined with subsequent immunotherapy was safe and improved survival outcomes in a subset of patients with recurrent GBM, according to results from a multi-institutional Phase I/II clinical trial co-led by researchers at The University of Texas MD Anderson Cancer Center and the University of Toronto.

The study, published today in Nature Medicine, met its primary safety endpoint and demonstrated the combination was well tolerated overall with no dose-limiting toxicities. The study did not meet its primary efficacy endpoint of objective response rate, but the combination achieved a 12-month overall survival (OS) rate of 52.7%, which is greater than the prespecified efficacy threshold of 20%. Three patients remained alive at 45, 48 and 60 months after treatment.

“This viral therapy is a different approach to the current standard of care,” said co-corresponding author Frederick Lang, M.D., chair of Neurosurgery. “Our previous trial demonstrated that not only does the virus act by killing cancer cells directly, it also effectively activates the innate immune system to convert these immunologically cold tumors into hot tumors. This led us to evaluate a combination with checkpoint inhibitors, which we now see can improve survival outcomes in a subset of patients.”

Clinically relevant deficiency of the “bonding hormone” oxytocin demonstrated

The hormones oxytocin and vasopressin are produced in the same area of the brain and are also very similar in structure. This is why disorders that cause vasopressin deficiency could also affect the neurons that produce oxytocin
Image Credit: Colin Behrens

The hormone oxytocin is important for social interaction and to control emotions. A deficiency of this hormone has previously been assumed, for example, in people with autism, but has never been proven. Now, for the first time, researchers from the University of Basel and the University Hospital of Basel have succeeded in demonstrating a deficiency of oxytocin in patients with a deficiency of vasopressin caused by a disease of the pituitary gland. This finding could be key to developing new therapeutic approaches.

The hormones oxytocin and vasopressin are produced in the same area of the brain and are also very similar in structure. Patients with a rare deficiency of vasopressin cannot concentrate their urine and lose liters of water as a result. In order to compensate for this loss, they are obliged to drink up to 10 liters or more per day.

With a nasal spray or a tablet containing synthetically produced vasopressin, these symptoms can usually be treated without any problems. However, even with this treatment, many patients report anxiety, have trouble with social interactions or demonstrate impaired emotional awareness.

Study reveals set of brain regions that control complex sequences of movement

The findings in mice have the potential to advance treatment of some brain injuries and illnesses
Photo Credit: Kanashi

In a novel set of experiments with mice trained to do a sequence of movements and "change course" at the spur of the moment, Johns Hopkins scientists report they have identified areas of the animals' brains that interact to control the ability to perform complex, sequential movements, as well as to help the mice rebound when their movements are interrupted without warning.

The research, they say, could one day help scientists find ways to target those regions in people and restore motor function caused by injury or illness.

Based on brain activity measurements of the specially trained rodents, the investigators found that three main areas of the cortex have distinct roles in how the mice navigate through a sequence of movements: the premotor, primary motor, and primary somatosensory areas. All are on the top layers of the mammals' brains and arranged in a fundamentally similar fashion in people.

The team concluded that the primary motor and primary somatosensory areas are involved in controlling the immediate movements of the mice in real time, while the premotor area appears to control an entire planned sequence of movements, as well as how the mice react and adjust when the sequence is unexpectedly disrupted.

Brain-Belly Connection: Gut Health May Influence Likelihood of Developing Alzheimer’s

UNLV study pinpoints 10 bacterial groups associated with Alzheimer’s disease, provides new insights into the relationship between gut makeup and dementia.
Illustration Credit: Julien Tromeur

Could changing your diet play a role in slowing or even preventing the development of dementia? We’re one step closer to finding out, thanks to a new UNLV study that bolsters the long-suspected link between gut health and Alzheimer’s disease.

The analysis — led by a team of researchers with the Nevada Institute of Personalized Medicine (NIPM) at UNLV and published this spring in the Nature journal Scientific Reports — examined data from dozens of past studies into the belly-brain connection. The results? There’s a strong link between particular kinds of gut bacteria and Alzheimer’s disease.

Between 500 and 1,000 species of bacteria exist in the human gut at any one time, and the amount and diversity of these microorganisms can be influenced by genetics and diet.

The UNLV team’s analysis found a significant correlation between 10 specific types of gut bacteria and the likelihood of developing Alzheimer’s disease. Six categories of bacteria — Adlercreutzia, Eubacterium nodatum group, Eisenbergiella, Eubacterium fissicatena group, Gordonibacter, and Prevotella9 — were identified as protective, and four types of bacteria — Collinsella, Bacteroides, Lachnospira, and Veillonella — were identified as a risk factor for Alzheimer’s disease.

The brain reacts differently to touch depending on context

Photo Credit: Thor Balkhed

The touch of another person may increase levels of the “feelgood” hormone oxytocin. But the context really matters. The situation impacts oxytocin levels not only in the moment, but also later, as is shown by researchers at Linköping University and the University of Skövde.

 An embrace from a parent, a warm hand on your shoulder or a caress from a romantic partner are examples of how touch can strengthen social bonds between people and influence emotions. But although touch and the sense of touch have a very important function, knowledge of how this actually works is still lacking.

Studies in animals have shown that the hormone oxytocin is linked to touch and social bonding. However, many questions remain unanswered when it comes to oxytocin’s role in human social interactions and how this hormone can influence and be influenced by the brain. To study this closer, researchers have examined what happens in the body when we feel a soft touch. India Morrison. 

Researchers develop model for how the brain acquires essential omega-3 fatty acids

Step-by-step process of lipid transport across blood-brain barrier.
Illustration Credit: Ethan Tyler from NIH Medical Arts

Researchers at the UCLA David Geffen School of Medicine, the Howard Hughes Medical Institute at UCLA and the National Institutes of Health have developed a zebrafish model that provides new insight into how the brain acquires essential omega-3 fatty acids, including docosahexaenoic acid (DHA) and linolenic acid (ALA). Their findings, published in Nature Communications, have the potential to improve understanding of lipid transport across the blood-brain barrier and of disruptions in this process that can lead to birth defects or neurological conditions. The model may also enable researchers to design drug molecules that are capable of directly reaching the brain.

Omega-3 fatty acids are considered essential because the body cannot make them and must obtain them through foods, such as fish, nuts and seeds. DHA levels are especially high in the brain and important for a healthy nervous system. Infants obtain DHA from breastmilk or formula, and deficiencies of this fatty acid have been linked to problems with learning and memory. To get to the brain, omega-3 fatty acids must pass through the blood-brain barrier via the lipid transporter Mfsd2a, which is essential for normal brain development. Despite its importance, scientists did not know precisely how Mfsd2a transports DHA and other omega-3 fatty acids.

The evolution of honey bee brains

European honey bee worker. The researchers studied honey bees exhibiting different behaviors: foragers, nurse bees, and queens. Honey bees in general have been a key insect model for better understanding learning and memory for more than 100 years.
Photo Credit: ©2023 Hiroki Kohno

Researchers have proposed a new model for the evolution of higher brain functions and behaviors in the Hymenoptera order of insects. The team compared the Kenyon cells, a type of neuronal cell, in the mushroom bodies (a part of the insect brain involved in learning, memory and sensory integration) of “primitive” sawflies and sophisticated honey bees. They found that three diverse, specialized Kenyon cell subtypes in honey bee brains appear to have evolved from a single, multifunctional Kenyon cell-subtype ancestor. In the future, this research could help us better understand the evolution of some of our own higher brain functions and behaviors.

Are you “busy as a bee,” a “social butterfly” or a “fly on the wall”? There are many ways we compare our behavior to that of insects, and as it turns out there may be more to it than just fun idioms. Studying insects could help us understand not only how their behavior has evolved, but also the behavior of highly evolved animals, including ourselves. Mammalian brains are big and complex, so it is difficult to identify which behaviors and neural and genetic changes have co-developed over time. By comparison, insect brains are much smaller and simpler, making them useful models for study.

Stress increases Alzheimer’s risk in female mice but not males

Stress causes the levels of Alzheimer's proteins to rise in females' brains but not males' brains, according to a new study in mice by researchers at Washington University School of Medicine in St. Louis. This difference may contribute to women's greater risk of developing Alzheimer's disease.
Photo Credit: Karolina Grabowska

Women are about twice as likely as men to be diagnosed with Alzheimer’s disease. Some of that is age; in the U.S., women outlive men by five to six years, and advanced age is the strongest risk factor for Alzheimer’s. But there’s more to it than that, so Alzheimer’s researchers continue to look for other reasons why women have an elevated risk of the deadly neurodegenerative disease.

Stress may be one such reason. A study by researchers at Washington University School of Medicine in St. Louis shows that the effect stress has on the brain differs by sex, at least in mice. In stressful situations, levels of the Alzheimer’s protein amyloid beta rises sharply in the brains of females but not males. In addition, the researchers identified a molecular pathway that is active in brain cells from female mice but not male mice, and showed that it accounts for the divergent responses to stress.

The findings, published May 2 in Brain, add to a growing collection of evidence that sex matters in health and disease. From cancer to heart disease to arthritis, scientists have found differences between males and females that could potentially affect how men and women respond to efforts to prevent or treat chronic diseases.

Scientists discover anatomical changes in the brains of the newly sighted

MIT neuroscientists discovered anatomical changes that occur in the white matter pathways linking visual-processing areas of the brain in children who have congenital cataracts surgically removed. This image shows the late-visual pathways in the brain.
Illustration Credit: Courtesy of the researchers, edited by MIT News

For many decades, neuroscientists believed there was a “critical period” in which the brain could learn to make sense of visual input, and that this window closed around the age of 6 or 7.

Recent work from MIT Professor Pawan Sinha has shown that the picture is more nuanced than that. In many studies of children in India who had surgery to remove congenital cataracts beyond the age of 7, he has found that older children can learn visual tasks such as recognizing faces, distinguishing objects from a background, and discerning motion.

In a new study, Sinha and his colleagues have now discovered anatomical changes that occur in the brains of these patients after their sight is restored. These changes, seen in the structure and organization of the brain’s white matter, appear to underlie some of the visual improvements that the researchers also observed in these patients.

The findings further support the idea that the window of brain plasticity, for at least some visual tasks, extends much further than previously thought.

Researchers develop technique for rapid detection of neurodegenerative diseases like Parkinson’s and CWD

Illustration Credit: Sang-Hyun Oh Research Group, University of Minnesota

University of Minnesota researchers have developed a groundbreaking new diagnostic technique that will allow for faster and more accurate detection of neurodegenerative diseases. The method will likely open a door for earlier treatment and mitigation of various diseases that affect humans, such as Alzheimer's and Parkinson's, and similar diseases that affect animals, such as chronic wasting disease (CWD).

Their new study is published in Nano Letters.

“This research mainly focuses on chronic wasting disease in deer, but ultimately our goal is to expand the technology for a broad spectrum of neurodegenerative diseases, Alzheimer’s and Parkinson’s being the two main targets,” said Sang-Hyun Oh, senior co-author of the paper and a professor in the College of Science and Engineering. “Our vision is to develop ultra-sensitive, powerful diagnostic techniques for a variety of neurodegenerative diseases so that we can detect biomarkers early on, perhaps allowing more time for the deployment of therapeutic agents that can slow down the disease progression. We want to help improve the lives of millions of people affected by neurodegenerative diseases.”

Targeting mitochondria and related protein suggest new therapeutic strategy for treating Lou Gehrig's disease (ALS)

Researchers have discovered a receptor, sigma-1 receptor (green), and a protein, ATAD3A (red),  that are associated with Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease.
Image Credit: Yamanaka Laboratory

Researchers at Nagoya University in Japan have discovered a receptor, sigma-1 receptor, and a protein, ATAD3A, that are associated with Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease. Since there are drugs that specifically target the receptor, their findings suggest a new therapeutic strategy. They published the study in the journal Neurobiology of Disease. 

ALS causes degeneration of motor neurons and the resulting muscle atrophy. Some of this degeneration is the result of the dysfunction of mitochondria, the energy-generating organelles of the body. This dysfunction causes a lack of energy in neurons resulting in the characteristic symptoms of the disease.   

The integrity of the mitochondria-associated membrane (MAM) is important for the stability of the mitochondria. The MAM is especially important during the processes of division of mitochondria (called fission) and mitochondria fusing together (called fusion). Several proteins, including enzymes, are associated with these processes and accumulate in the MAM.  

Drug for rare form of ALS approved by FDA

A new drug has been approved by the Food and Drug Administration (FDA) for a rare, inherited form of amyotrophic lateral sclerosis (ALS). Called tofersen, the drug — developed by Biogen Inc. and based in part on research conducted at Washington University School of Medicine in St. Louis — slows the progression of the deadly, paralyzing disease. 

Video Credit: Huy Mach and Tamara Bhandari

A new drug has been approved by the Food and Drug Administration (FDA) for a rare, inherited form of amyotrophic lateral sclerosis (ALS), a paralyzing neurological disease. Known as tofersen, the drug has been shown to slow progression of the deadly disease. International clinical trials of tofersen, developed by the global biotechnology company Biogen Inc., were led by a neurologist at Washington University School of Medicine in St. Louis.

Tofersen, also known by the brand name Qalsody, is designed for ALS patients whose disease is caused by mutations in the gene SOD1. In the phase 3 clinical trial, the drug reduced molecular signs of disease and curbed neurodegeneration in the first six months of use. Over longer time frames, some participants experienced a stabilization of muscle strength and control.

The drug is approved under the accelerated approval pathway, under which FDA may approve drugs for serious conditions where there is an unmet medical need and a drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients.

Brain circuits for locomotion evolved long before appendages and skeletons

The sea slug, Pleurobranchea californica 
Photo Credit: Fred Zwicky

Hundreds of millions of years before the evolution of animals with segmented bodies, jointed skeletons or appendages, soft-bodied invertebrates like sea slugs ruled the seas. A new study finds parallels between the brain architecture that drives locomotion in sea slugs and that of more complex segmented creatures with jointed skeletons and appendages. 

Reported in the Journal of Neuroscience, the study suggests that, rather than developing an entirely new set of neural circuits to govern the movement of segmented body parts, the insects, crustaceans and even vertebrates like mammals adapted a network of neurons, a module, that guided locomotion and posture in much simpler organisms. 

“Sea slugs may still have that module, a smallish network of neurons called the ‘A-cluster,’ with 23 neurons identified so far,” said University of Illinois Urbana-Champaign molecular and integrative physiology professor Rhanor Gillette, who led the new research. 

“The question that we addressed in this study is whether the similarities we see between sea slugs and more complex creatures evolved independently or whether those with segmented body parts and appendages may have inherited their underlying neural circuitry from a soft-bodied, bilaterally symmetrical common ancestor,” he said. 

Study links nutrients, brain structure, cognition in healthy aging

In a study of older adults, a research team led by, from left, Christopher Zwilling, Tanveer Talukdar and Aron Barbey found that blood markers of two saturated fatty acids, along with certain omega-6, -7 and -9 fatty acids, correlated with better scores on tests of memory and were associated with larger brain structures in the frontal, temporal, parietal and insular cortices. 
Photo Credit: Fred Zwicky

In a new study, scientists explored the links between three measures known to independently predict healthy aging: nutrient intake, brain structure and cognitive function. Their analysis adds to the evidence that these factors jointly contribute to brain health in older adults. 

Reported in the Journal of Nutrition, the study found that blood markers of two saturated fatty acids, along with certain omega-6, -7 and -9 fatty acids, correlated with better scores on tests of memory and with larger brain structures in the frontal, temporal, parietal and insular cortices. 

While other studies have found one-to-one associations between individual nutrients or classes of nutrients and specific brain regions or functions, very little research takes a comprehensive look at brain health, cognition and broad dietary patterns overall, said Aron Barbey, a professor of psychology, bioengineering and neuroscience at the University of Illinois Urbana-Champaign who led the study with postdoctoral researcher Tanveer Talukdar and psychology research scientist Chris Zwilling. The three co-authors are all affiliated with the Beckman Institute for Advanced Science and Technology at the U. of I. 

Effects of brain stimulation can be conditioned

Brain activity can be stimulated with transcranial magnetic stimulation.
Photo Credit: © RUB, Marquard

What worked with Pavlov's dog also works with an artificially induced change in nerve cell activity.

Researchers at the Ruhr University Bochum have succeeded in a special form of classic conditioning. In a group of 75 people, they showed that effects of transcranial magnetic stimulation, or TMS for short, can only be triggered by hearing a sound. Prof. Dr. Burkhard Pleger from the neurology of the Bergmannsheil University Hospital describes the results together with doctoral students Stefan Ewers and Timo Dreier as well as other colleagues in the journal Scientific Reports.

Magnetic stimulation causes the thumb muscle to contract

For the TMS, a magnetic coil is placed from the outside over a specific part of the brain. The strong magnetic field stimulates the underlying nerve cells to act. If you stimulate a certain area of the motor cortex in this way, the index finger or the thumb moves, for example. The Bochum team used the so-called paired pulse TMS stimulation for its work. Two TMS stimuli followed each other every twelve milliseconds, which leads to a stronger contraction of a muscle on the thumb than a TMS individual stimulation. In the conditioning phase, the researchers always combined these paired pulses TMS with a tone that the participants were presented via headphones parallel to the TMS stimulus.