#neurodegenerative diseases
In a new study published in Applied Physiology, Nutrition, and Metabolism, scientists from the University of Guelph have found that exercise has the potential to decrease toxic build-up in the brain, reducing the severity of brain disorders such as Huntington’s disease.
Glutamate, an amino acid that is one of the twenty amino acids used to construct proteins, is used by the brain to transmit signals, but too much glutamate blocks future signals and can lead to toxicity in the brain. Since the majority of the brain relies on glutamate as the main neurotransmitter for communication between neural cells, it is essential that glutamate is reabsorbed and disposed of to prevent blockage. While glutamate reuptake is a normal process for healthy brains, several diseases such as Huntington’s disease, ALS, and epilepsy result in either failed reuptake of glutamate or high levels of glutamate in the brain. This can lead to unwanted and in some cases excessive stimulation of neighbouring cells which can worsen the disease.
The findings of this study show that exercise has the potential to increase the use of glutamate in the brain and may help reduce the toxicity caused by glutamate build-up in these diseases. “As we all know, exercise is healthy for the rest of the body and our study suggests that exercise may present an excellent option for reducing the severity of brain disorders” says Dr. Eric Herbst, lead author of the study. “Taking into account that there are no cures for neurodegenerative diseases where glutamate is implicated, this study offers another example of the benefits of exercise for our brains” continued Dr. Herbst. “In short, these findings offer another reason to exercise with the aim of either preventing or slowing the neurodegeneration caused by these disorders”.
The findings of this study are of particular importance to other researchers exploring different approaches to treating brain disorders. The main approaches to treating neurodegenerative diseases are hindered by the need to produce drugs that both have the intended effect for treating the disease and are also able to pass the blood brain barrier. Through the use of exercise, the brain can direct glutamate to be used as an energy source to dispose of excess amounts of the neurotransmitter, without relying on the difficult development of pharmaceuticals. Identifying and targeting the mechanisms that increase glutamate metabolism in the brain may also provide the medical field with additional ways of treating problems within the brain. How the findings of this study translates to people affected by neurodegenerative diseases still needs exploring and is an important next step.
Scientists identify the cause of Alzheimer’s progression in the brain
For the first time, researchers have used human data to quantify the speed of different processes that lead to Alzheimer’s disease and found that it develops in a very different way than previously thought. Their results could have important implications for the development of potential treatments.
The international team, led by the University of Cambridge, found that instead of starting from a single point in the brain and initiating a chain reaction which leads to the death of brain cells, Alzheimer’s disease reaches different regions of the brain early. How quickly the disease kills cells in these regions, through the production of toxic protein clusters, limits how quickly the disease progresses overall.
The researchers used post-mortem brain samples from Alzheimer’s patients, as well as PET scans from living patients, who ranged from those with mild cognitive impairment to those with late-stage Alzheimer’s disease, to track the aggregation of tau, one of two key proteins implicated in the condition.
In Alzheimer’s disease, tau and another protein called amyloid-beta build up into tangles and plaques – known collectively as aggregates – causing brain cells to die and the brain to shrink. This results in memory loss, personality changes and difficulty carrying out daily functions.
By combining five different datasets and applying them to the same mathematical model, the researchers observed that the mechanism controlling the rate of progression in Alzheimer’s disease is the replication of aggregates in individual regions of the brain, and not the spread of aggregates from one region to another.
The results, reported in the journal Science Advances, open up new ways of understanding the progress of Alzheimer’s and other neurodegenerative diseases, and new ways that future treatments might be developed.
For many years, the processes within the brain which result in Alzheimer’s disease have been described using terms like ‘cascade’ and ‘chain reaction’. It is a difficult disease to study, since it develops over decades, and a definitive diagnosis can only be given after examining samples of brain tissue after death.
For years, researchers have relied largely on animal models to study the disease. Results from mice suggested that Alzheimer’s disease spreads quickly, as the toxic protein clusters colonise different parts of the brain.
“The thinking had been that Alzheimer’s develops in a way that’s similar to many cancers: the aggregates form in one region and then spread through the brain,” said Dr Georg Meisl from Cambridge’s Yusuf Hamied Department of Chemistry, the paper’s first author. “But instead, we found that when Alzheimer’s starts there are already aggregates in multiple regions of the brain, and so trying to stop the spread between regions will do little to slow the disease.”
This is the first time that human data has been used to track which processes control the development of Alzheimer’s disease over time. It was made possible in part by the chemical kinetics approach developed at Cambridge over the last decade which allows the processes of aggregation and spread in the brain to be modelled, as well as advances in PET scanning and improvements in the sensitivity of other brain measurements.
“This research shows the value of working with human data instead of imperfect animal models,” said co-senior author Professor Tuomas Knowles, also from the Department of Chemistry. “It’s exciting to see the progress in this field – fifteen years ago, the basic molecular mechanisms were determined for simple systems in a test tube by us and others; but now we’re able to study this process at the molecular level in real patients, which is an important step to one day developing treatments.”
The researchers found that the replication of tau aggregates is surprisingly slow – taking up to five years. “Neurons are surprisingly good at stopping aggregates from forming, but we need to find ways to make them even better if we’re going to develop an effective treatment,” said co-senior author Professor Sir David Klenerman, from the UK Dementia Research Institute at the University of Cambridge. “It’s fascinating how biology has evolved to stop the aggregation of proteins.”
The researchers say their methodology could be used to help the development of treatments for Alzheimer’s disease, which affects an estimated 44 million people worldwide, by targeting the most important processes that occur when humans develop the disease. In addition, the methodology could be applied to other neurodegenerative diseases, such as Parkinson’s disease.
“The key discovery is that stopping the replication of aggregates rather than their propagation is going to be more effective at the stages of the disease that we studied,” said Knowles.
The researchers are now planning to look at the earlier processes in the development of the disease, and extend the studies to other diseases such as Frontal temporal dementia, traumatic brain injury and progressive supranuclear palsy where tau aggregates are also formed during disease.
(Image caption: SumaLateral Whole Brain Image. Credit: National Institute of Mental Health, National Institutes of Health, USA)
New research “sniffs out” how associative memories are formed
Has the scent of freshly baked chocolate chip cookies ever taken you back to afternoons at your grandmother’s house? Has an old song ever brought back memories of a first date? The ability to remember relationships between unrelated items (an odor and a location, a song and an event) is known as associative memory.
Psychologists began studying associative memory in the 1800s, with William James describing the phenomenon in his 1890 classic The Principles of Psychology. Scientists today agree that the structures responsible for the formation of associative memory are found in the medial temporal lobe, or the famous “memory center” of the brain, but the particular cells involved, and how those cells are controlled, have remained a mystery until now.
Neuroscientists at the University of California, Irvine have discovered specific types of neurons within the memory center of the brain that are responsible for acquiring new associative memories. Additionally, they have discovered how these associative memory neurons are controlled. We rely on associative memories in our everyday lives and this research is an important step in understanding the detailed mechanism of how these types of memories are formed in the brain.
“Although associative memory is one of the most basic forms of memory in our everyday life, mechanisms underlying associative memory remain unclear” said lead researcher Kei Igarashi, faculty fellow of the Center for the Neurobiology of Learning and Memory and assistant professor of anatomy & neurobiology at the UCI School of Medicine.
The study published in the journal Nature reports for the first time that specific cells in the lateral entorhinal cortex of the medial temporal lobe, called fan cells, are required for the acquisition of new associative memories and that these cells are controlled by dopamine, a brain chemical known to be involved in our experience of pleasure or reward.
In the study, researchers used electrophysiological recordings and optogenetics to record and control activity from fan cells in mice as they learn to associate specific odors with rewards. This approach led researchers to discover that fan cells compute and represent the association of the two new unrelated items (odor and reward). These fan cells are required for successful acquisition of new associative memories. Without these cells, pre-learned associations can be retrieved, but the new associations cannot be acquired. Additionally acquiring new associations also requires dopamine.
“We never expected that dopamine is involved in the memory circuit. However, when the evidence accumulated, it gradually became clear that dopamine is involved,” said Igarashi. “These experiments were like a detective story for us, and we are excited about the results.”
This discovery is an important piece in the puzzle of understanding how memories are formed in the brain and lays a foundation on which other researchers can continue to build. Associative memory abilities are known to decline in neurodegenerative diseases like Alzheimer’s Disease. Understanding the neurobiological mechanism of how these memories are formed is the first step to developing therapeutics to slow the loss of associative memory abilities in Alzheimer’s Disease.
Two Queens join forces in the fight against neurodegenerative diseases
Two queens, one still on the throne, one emerita, and a common cause. Queen Silvia of Sweden and Queen Sofía of Spain have joined forces in Salamanca for the Global Summit Neuro.
Upon arrival, both Queens were welcomed by many authorities, including the Government Delegate in the Castilla y León Autonomic Province, the Mayor of Salamanca, the Undersecretary of Health and the Dean of Salamanca…
