Neuroscience
Month
Humans may be endowed with the ability to perform complex forms of learning, attention and function but the evolutionary process that led to this has put us at risk of mental illness.
Data from new research, published today in the journal Nature Neuroscience, was analysed by Dr Richard Emes, a bioinformatics expert from the School of Veterinary Medicine and Science at The University of Nottingham. The results showed that disease-causing mutations occur in the genes that evolved to make us smarter than our fellow animals.
Dr Emes, Director of The University of Nottingham’s Advanced Data Analysis Centre, conducted an analysis of the evolutionary history of the Discs Large homolog (Dlg) family of genes which make some of the essential building blocks of the synapse — the connection between nerve cells in the brain. He said: “This study highlights the importance of the synapse proteome — the proteins involved in the brains signalling processes — in the understanding of cognition and the power of comparative studies to investigate human disease.”
The study involved scientists from The University of Edinburgh, The Wellcome Trust Sanger Institute, the University of Aberdeen, The University of Nottingham and the University of Cambridge.
This cross-disciplinary team of experts carried out what they believe to be the first genetic dissection of the vertebrate’s ability to perform complex forms of learning, attention and function. They focussed on Dlg — a family of genes that humans shared with the ancestor of all backboned animals some 550 million years ago. Gene families like the Dlgs arose by duplication of DNA, changed by mutation over millions of years and now contribute to the complex cognitive processes we have today. However, this redundancy and subsequent accumulation of changes in the DNA may have led to increased susceptibility to some diseases.
Components of the human cognitive repertoire are routinely assessed by using computerised touch-screen methods. By using the same technique with mice researchers were able to probe the cognitive mechanisms conserved since humans and mice shared a common ancestor — around 100 million years ago. By comparing the effect of DNA changes on behavioural test outcomes this research showed a common cause of mutation and effect of learning changes in both mice and humans.
Dr Emes said: “This research shows the importance of discerning information from data and how the power of computational research combined with behavioural and cognitive studies can provide such novel insight into the basis of clinical disorders. This research provides continued support that discovery occurs at the boundary of disciplines by the integration of data.”
(Image Credit: Stanford University)
A team of brain cancer researchers at Barrow Neurological Institute at St. Joseph’s Hospital and Medical Center has effectively treated brain tumor cells using a unique combination of diet and radiation therapy. The study, “The Ketogenic Diet Is an Effective Adjuvant to Radiation Therapy for the Treatment of Malignant Glioma,” was published in PLOS ONE.
Led by Adrienne C. Scheck, PhD, Principal Investigator in Neuro-Oncology and Neurosurgery Research at Barrow, the groundbreaking research studied the effects of the ketogenic diet in conjunction with radiation therapy for the treatment of malignant gliomas, an aggressive and deadly type of brain tumor. The ketogenic diet is a high-fat, low-carbohydrate diet that alters metabolism and is used in the treatment of pediatric epilepsy that does not respond to conventional therapies. The diet’s affects on brain homeostasis have potential for the treatment of other neurological diseases, as well.
In the study, mice with high-level malignant gliomas were maintained on either a standard or a ketogenic diet. Both groups received radiation therapy. Dr. Scheck’s team discovered that animals fed a ketogenic diet had an increased median survival of approximately five days relative to animals maintained on a standard diet. Of the mice that were fed a ketogenic diet and received radiation, nine of 11 survived with no signs of tumor recurrence, even after being switched back to standard food, for over 200 days. None on the standard diet survived more than 33 days.
One theory behind the success of the treatment is that the ketogenic diet may reduce growth factor stimulation, inhibiting tumor growth. Barrow scientists also believe that it may reduce inflammation and edema surrounding the tumors. This is believed to be the first study of its kind to look at the effects of the ketogenic diet with radiation.
Dr. Scheck believes that the study has promising implications in the treatment of human malignant gliomas. “We found that the ketogenic diet significantly enhances the anti-tumor effect of radiation, which suggests that it may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas,” she says.
Dr. Scheck adds that the ketogenic diet could quickly and easily be added into current brain tumor treatment plans as an adjuvant therapy without the need for FDA approval. She is currently exploring options for clinical trials.
The classic theory of the brain is one of connections, in which the brain consists of a network of neurons that interact with each other to allow us to think, see, interpret, and understand the world around us. In this model, called distributed representation, an individual neuron by itself has no inherent meaning, but only contributes to a pattern of neuronal activity that has meaning. For example, a certain pattern of many neurons fires when you think “dog” and another pattern for “cat.”
"The belief in distributed representation theory is that a concept or object is not represented by a single neuron in the brain but by a pattern of activations over a number of neurons," explains Asim Roy, a professor of information systems at Arizona State University, to Medical Xpress . "Thus there is no single neuron in the brain representing a cat or a dog. Proponents of this theory claim that a cat or a dog is represented by its microfeatures such as legs, ears, body, tail, and so on. However, they think that neurons have absolutely no meaning on a stand-alone basis. Therefore, they go further and claim that these microfeatures are at the subsymbolic level, which means that meaning arises only when you consider the pattern of activations as a whole. Therefore, there are no neurons representing legs, ears, body, tail, etc. The representation is at a much lower level."
Roy is among a number of scientists working in the fields of neuroscience and artificial intelligence (AI) who suspect that the brain may not be as connected as distributed representation suggests. The basis of their alternative model, called localist representation, is that a single neuron can represent a dog, a cat, or any other object or concept. These neurons can be considered symbols since they have meaning on a stand-alone basis. However, as Roy explains, this doesn’t necessarily mean only one neuron represents a dog; such “concept cells” are high-level neurons, which fire in response to the firing of an assortment of low-level neurons that represent the legs, ears, body, tail, etc.
"In localist representation, there could be separate neurons for a dog and a cat, and also neurons for legs, ears, body, tail, etc.," he said. "It’s very similar to the model in my paper for word recognition, which is an old model from James McClelland [Chair of the Psychology Department at Stanford University] and [the late pioneering neuroscientist] David Rumelhart. You have low-level neurons that detect letters of the alphabet and then high-level neurons for individual words. So letter neurons and word neurons, they both exist."
The origins of this dispute between localist and distributed representation goes back to the early ’80s, to a dispute between the symbol processing hypothesis of artificial intelligence (AI) and the subsymbolic paradigm of connectionists. In the past 30 years, the debate has only intensified.
A scientist at the University of British Columbia and Vancouver Coastal Health has identified the molecule that controls a scissor-like protein responsible for the production of plaques – the telltale sign of Alzheimer’s disease (AD).
The molecule, known as GSK3-beta, activates a gene that creates a protein, called BACE1. When BACE1 cuts another protein, called APP, the resulting fragment – known as amyloid beta – forms tiny fibers that clump together into plaques in the brain, eventually killing neural cells.
Using an animal model, Dr. Weihong Song, Canada Research Chair in Alzheimer’s Disease and professor of psychiatry, found that disabling GSK3-beta’s effect in mice resulted in less BACE1 and far fewer deposits of amyloid in their brains. Song’s research, published online in the Journal of Clinical Investigation, also found that such mice performed better than untreated mice on memory tests.
Previous research had shown that GSK3-beta spurred the growth of twisted fibers inside neurons, known as tangles – another hallmark of AD. Song says his discovery of the protein’s dual destructiveness makes it a promising target for drug research.
GSK3-beta, however, is a versatile enzyme that controls many vital physiological functions. The drug used to inhibit GSK3-beta in the mice is too indiscriminate, and could cause several serious side effects, including cancer.
“If we can find a way to stop GSK3-beta’s specific reaction with BACE1, and still leave it intact to perform other crucial tasks, we have a much better chance of treating AD and preventing its progression,” says Song, a member of the Brain Research Centre at UBC and the Vancouver Coastal Health Research Institute (VCHRI), and Director of the Townsend Family Laboratories at UBC.
Surgeons may soon be able to regrow patients’ nerves, such as those in damaged spinal cords, using technology adapted from the type of inkjet printer most of us have connected to our computer at home.
The ink has to keep the cells in suspension, as well as having the right chemical composition to keep them alive. It also protects them as they are shot out of the printer at amazing speeds.
The scaffolds act as the base upon which the cells thrive, and contain substances such as growth factor molecules and electrical conduits to enable stimulation to promote cell growth. The aim is to produce structures up to 4 cm long, which can be “patched” into broken or damaged nerves or muscles.
“There’s great interest from the medical world, and we are working closely with clinicians at St Vincents Hospital in Melbourne,” says Prof Gordon Wallace, director of the Materials node of ANFF and ACES. “They’re very interested in the possibilities it raises, and the collaboration is resulting in new ideas almost every week.”
“The support from ANFF and the collaborative, interdisciplinary approach that our facilities bring has attracted the best people in the world to join our teams,” he adds.
A Loyola University Medical Center neurologist is reporting surprising results of a study of patients who experience both epileptic and non-epileptic seizures.
Non-epileptic seizures resemble epileptic seizures, but are not accompanied by abnormal electrical discharges. Rather, these seizures are believed to be brought on by psychological stresses.
Dr. Diane Thomas reported that 15.7 percent of hospital patients who experienced non-epileptic seizures also had epileptic seizures during the same hospital stay. Previous studies found the percentage of such patients experiencing both types of seizures was less than 10 percent.
Thomas reported the findings Dec. 2 at a meeting of the American Epilepsy Society.
The finding is significant because epileptic and non-epileptic seizures are treated differently. Non-epileptic seizures do not respond to epilepsy medications, and typically are treated with psychotherapy, anti-depressants, or both, Thomas said.
Non-epileptic seizures used to be called pseudoseizures. But they are quite real, and the preferred term now is psychogenic non-epileptic seizure. A non-epileptic seizure can resemble the convulsions characteristic of a grand mal epileptic seizure, or the staring-into-space characteristic of a petit mal epileptic seizure. But unlike an epileptic seizure, the brain waves during a non-epileptic seizure are normal.
Non-epileptic seizures can be triggered by stresses such as physical or sexual abuse, incest, job loss, divorce or death of a loved one. In some cases, the traumatic event may be blocked from the patient’s conscious memory.
Non-epileptic seizures often are mistaken for epileptic seizures. While some patients who have both types can distinguish between the two, others find it difficult to distinguish when they are having non-epileptic seizures.
The only way to make a definitive seizure diagnosis is to monitor a patient with an electroencephalogram (EEG) and a video camera. (The EEG can detect abnormal electrical discharges that indicate an epileptic seizure.) The patient is monitored with the camera until a seizure occurs, and the EEG recordings from the event are then analyzed.
Thomas conducted her study at the University of Maryland Medical Center, where she did a fellowship in epilepsy before recently joining Loyola. Thomas and colleagues reviewed 256 patients who had come to the hospital to have their seizures monitored. Seventy of the patients had documented non-epileptic seizures. Of these, 11 patients (15.7 percent) also experienced epileptic seizures during their hospital stays.
Forgive your mind this minor annoyance because it has worked to save your life—or more accurately, the lives of your ancestors. Most likely you have not needed to worry whether the rustling in the underbrush is a rabbit or a leopard, or had to identify the best escape route on a walk by the lake, or to wonder whether the funny pattern in the grass is a snake or dead branch. Yet these were life-or-death decisions to our ancestors. Optimal moment-to-moment readiness requires a brain that is working constantly, an effort that takes a great deal of energy. (To put this in context, the modern human brain is only 2 percent of our body weight, but it uses 20 percent of our resting energy.) Such an energy-hungry brain, one that is constantly seeking clues, connections and mechanisms, is only possible with a mammalian metabolism tuned to a constant high rate.
Constant thinking is what propelled us from being a favorite food on the savanna—and a species that nearly went extinct—to becoming the most accomplished life-form on this planet. Even in the modern world, our mind always churns to find hazards and opportunities in the data we derive from our surroundings, somewhat like a search engine server. Our brain goes one step further, however, by also thinking proactively, a task that takes even more mental processing.
So even though most of us no longer worry about leopards in the grass, we do encounter new dangers and opportunities: employment, interest rates, “70 percent off” sales and swindlers offering $20 million for just a small investment on our part. Our primate heritage brought us another benefit: the ability to navigate a social system. As social animals, we must keep track of who’s on top and who’s not and who might help us and who might hurt us. To learn and understand this information, our mind is constantly calculating “what if?” scenarios. What do I have to do to advance in the workplace or social or financial hierarchy? What is the danger here? The opportunity?
For these reasons, we benefit from having a brain that works around the clock, even if it means dealing with intrusive thoughts from time to time.
Scientists at the Gladstone Institutes have defined for the first time a key underlying process implicated in multiple sclerosis (MS)—a disease that causes progressive and irreversible damage to nerve cells in the brain and spinal cord. This discovery offers new hope for the millions who suffer from this debilitating disease for which there is no cure.
Researchers in the laboratory of Gladstone Investigator Katerina Akassoglou, PhD, have identified in animal models precisely how a protein that seeps from the blood into the brain sets off a response that, over time, causes the nerve cell damage that is a key indicator of MS. These findings, which are reported in the latest issue of Nature Communications, lay the groundwork for much-needed therapies to treat this disease.
Professor José Miguel Soria, a member of the Institute of Biomedical Sciences, Universidad CEU Cardenal Herrera, has co-directed with Professor Manuel Monleón of the Universitat Politècnica de València a study on the compatibility of polymeric biomaterials in the brain and its effectiveness to favour neuroregeneration in areas with some kind of damage or brain injury.
The research carried out has shown that these types of implants, made of a biocompatible synthetic material, are colonized within two months by neural progenitor cells and irrigated by new blood vessels. This allows the generation, within these structures, of new neurons and glia, capable of repairing injured brain tissue caused by trauma, stroke or neurodegenerative disease, among other causes.
The synthetic structures used in this study are made with a porous and biocompatible polymeric material called acrylate copolymer. In the first phase of the project, the structures have been studied in vitro by implanting them into neural tissue, and subsequently also in vivo, when implanted in two areas of the adult rat brain: the cerebral cortex and the subventricular zone, the most important source of generation of adult neural stem cells.
The study has confirmed the high biocompatibility of polymeric materials, such as acrylate copolymer, with brain tissue and opens new possibilities of the effectiveness of the implementation of these structures in the brain, seeking optimum location for developing regenerative strategies of the central nervous system.
Furthermore, the results are particularly relevant when one considers that in the adult brain neuroregeneration capacity is more limited than in younger individuals and that the main impediment for this is the lack of revascularization of damaged tissue, something that the biomaterial studied has shown to favour.