Too much of calcium in brain may cause Parkison's disease, says study

Agencies
February 21, 2018

Washington, Feb 21: A new study has found excessive calcium levels in the brain are behind Parkinson's disease.

The findings of the international team, led by the University of Cambridge, represent another step towards understanding how and why people develop Parkinson's.

They found that calcium can mediate the interaction between small membranous structures inside nerve endings, which are important for neuronal signalling in the brain, and alpha-synuclein, the protein associated with Parkinson's disease.

Excess levels of either calcium or alpha-synuclein may be what starts the chain reaction that leads to the death of brain cells.

Parkinson's disease is one of a number of neurodegenerative diseases caused when naturally occurring proteins fold into the wrong shape and stick together with other proteins, eventually forming thin filament-like structures called amyloid fibrils. These amyloid deposits of aggregated alpha-synuclein, also known as Lewy bodies, are the sign of Parkinson's disease.

Curiously, it hasn't been clear until now what alpha-synuclein actually does in the cell: why it's there and what it's meant to do. It is implicated in various processes, such as the smooth flow of chemical signals in the brain and the movement of molecules in and out of nerve endings, but exactly how it behaves is unclear.

"Alpha-synuclein is a very small protein with very little structure, and it needs to interact with other proteins or structures in order to become functional, which has made it difficult to study," said senior author Dr Gabriele Kaminski Schierle from Cambridge's Department of Chemical Engineering and Biotechnology.

Thanks to super-resolution microscopy techniques, it is now possible to look inside cells to observe the behaviour of alpha-synuclein. To do so, Kaminski Schierle and her colleagues isolated synaptic vesicles, part of the nerve cells that store the neurotransmitters which send signals from one nerve cell to another.

In neurons, calcium plays a role in the release of neurotransmitters. The researchers observed that when calcium levels in the nerve cell increase, such as upon neuronal signalling, the alpha-synuclein binds to synaptic vesicles at multiple points causing the vesicles to come together. This may indicate that the normal role of alpha-synuclein is to help the chemical transmission of information across nerve cells.

"This is the first time we've seen that calcium influences the way alpha-synuclein interacts with synaptic vesicles," said Dr Janin Lautenschlger, the paper's first author. "We think that alpha-synuclein is almost like a calcium sensor. In the presence of calcium, it changes its structure and how it interacts with its environment, which is likely very important for its normal function."

"There is a fine balance of calcium and alpha-synuclein in the cell, and when there is too much of one or the other, the balance is tipped and aggregation begins, leading to Parkinson's disease," said co-first author Dr Amberley Stephens.

The imbalance can be caused by a genetic doubling of the amount of alpha-synuclein (gene duplication), by an age-related slowing of the breakdown of excess protein, by an increased level of calcium in neurons that are sensitive to Parkinson's, or an associated lack of calcium buffering capacity in these neurons.

Understanding the role of alpha-synuclein in physiological or pathological processes may aid in the development of new treatments for Parkinson's disease. One possibility is that drug candidates developed to block calcium, for use in heart disease for instance, might also have potential against Parkinson's disease.

The findings have been reported in the journal Nature Communications.

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Agencies
January 25,2020

Washington D.C., Jan 25: A new study conducted by a team of researchers reveals why individuals who have a history of early life adversity (ELA) are disproportionately prone to opioid addiction.

The study conducted examined how early adversities interact with factors such as increased access to opioids to directly influence brain development and function, causing a higher potential for opioid addiction.

The study was lead by UCI researchers and was published in Molecular Psychiatry.

Tallie Z. Baram, MD, PhD, the Danette Shepard Chair in Neurological Sciences at the UCI School of Medicine and one of the senior researchers for the study, was on the take that the widely known factor genetics that plays major role in addiction vulnerability, cannot be solely held responsible for the recent rise in opioid abuse.

To further clarify, the researchers simulated ELA in rats by limiting bedding and nesting materials during a short, postnatal period of time.

In female rats, this led to striking opioid addiction-like characteristics including an increased relapse- behaviour, for example.

As observed in addicted humans, the rats were willing to work very hard (pay a very high price) to obtain the drug.

Baram said: "Ultimately, we found that conditions during sensitive developmental periods can lead to vulnerability to the addictive effects of opioid drugs, especially in females, which is consistent with the prevalence of ELA in heroin-addicted women."

These findings can be used to highlight the importance given to sex differences in future ELA-related studies on opioid addiction, and in future prevention or intervention strategies being developed to address the growing opioid crisis.

The study conducted examined how early adversities interact with factors such as increased access to opioids to directly influence brain development and function, causing a higher potential for opioid addiction.

The study was lead by UCI researchers and was published in Molecular Psychiatry.

The study found that unpredictable, fragmented early life environments may lead to abnormal maturation of certain brain circuits, which profoundly impacts brain function and persists into adolescence and adulthood.

Tallie Z. Baram, MD, PhD, the Danette Shepard Chair in Neurological Sciences at the UCI School of Medicine and one of the senior researchers for the study, was on the take that the widely known factor genetics that plays major role in addiction vulnerability, cannot be solely held responsible for the recent rise in opioid abuse.

To further clarify, the researchers implanted ELA in rats by limiting bedding and nesting materials during a short, postnatal period of time.

In female rats, this led to striking opioid addiction-like characteristics including an increased relapse- behaviour, for example.

As observed in addicted humans, the rats were willing to work very hard (pay a very high price) to obtain the drug.

Baram said: "Ultimately, we found that conditions during sensitive developmental periods can lead to vulnerability to the addictive effects of opioid drugs, especially in females, which is consistent with the prevalence of ELA in heroin-addicted women."

These findings can be used to highlight the importance given to sex differences in future ELA-related studies on opioid addiction, and in future prevention or intervention strategies being developed to address the growing opioid crisis.

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Agencies
July 24,2020

Colorado, Jul 24: A new study has found that physical stress in one's job may be associated with faster brain ageing and poorer memory.

Aga Burzynska, an assistant professor in the Department of Human Development and Family Studies, and her research team connected occupational survey responses with brain-imaging data from 99 cognitively normal older adults, age 60 to 79. They found that those who reported high levels of physical stress in their most recent job had smaller volumes in the hippocampus and performed poorer on memory tasks. The hippocampus is the part of the brain that is critical for memory and is affected in both normal ageing and in dementia.

Their findings were published this summer in Frontiers in Human Neuroscience under the research topic 'Work and Brain Health Across the Lifespan.'

"We know that stress can accelerate physical ageing and is the risk factor for many chronic illnesses," Burzynska said. "But this is the first evidence that occupational stress can accelerate brain and cognitive ageing."

She added that it is important to understand how occupational exposures affect the ageing of our brains.

"An average American worker spends more than eight hours at work per weekday, and most people remain in the workforce for over 40 years," Burzynska said. "By pure volume, occupational exposures outweigh the time we spend on leisure social, cognitive and physical activities, which protect our ageing minds and brains."

Physical demands at work

Burzynska explained that the association between "physical stress" and brain/memory were driven by physical demands at work. These included excessive reaching, or lifting boxes onto shelves, not necessarily aerobic activity. This is important because earlier work by Burzynska and her colleagues showed that leisure aerobic exercise is beneficial for brain health and cognition, from children to very old adults. Therefore, the researchers controlled for the effects of leisure physical activity and exercise.

As expected, leisure physical activity was associated with greater hippocampal volume, but the negative association with physical demands at work persisted.

"This finding suggests that physical demands at work may have parallel yet opposing associations with brain health," Burzynska explained. "Most interventions for postponing cognitive decline focus on leisure, not on your job. It's kind of unknown territory, but maybe future research can help us make some tweaks to our work environment for long-term cognitive health."

She added that the results could have important implications for society.

"Caring for people with cognitive impairment is so costly, on economic, emotional and societal levels," Burzynska said. "If we can support brain health earlier, in middle-aged workers, it could have an enormous impact."

The researchers considered and corrected for several other factors that could be related to work environment, memory and hippocampus, such as age, gender, brain size, educational level, job title, years in the occupation and general psychological stress.

One piece of the puzzle

"The research on this topic is so fragmented," Burzynska said. "One previous study linked mid-life managerial experience with greater hippocampus volume in older age. Another showed that taxi drivers had larger hippocampi than a city's bus drivers, presumably due to the need to navigate. In our study, job complexity and psychological stress at work were not related to hippocampal volume and cognition. Clearly, our study is just one piece of the puzzle, and further research is needed."

The magnetic resonance imaging (MRI) data used for the study was collected at the University of Illinois Urbana-Champaign between 2011 and 2014.

CSU researchers now can collect MRI data with the new 3T scanner at the University's Translational Medicine Institute.

With this new capability, Burzynska, along with Michael Thomas and Lorann Stallones of CSU's Department of Psychology, is launching a new project, "Impact of Occupational Exposures and Hazards on Brain and Cognitive Health Among Aging Agricultural Workers," which will involve collecting MRI brain scans and identifying risk and protective factors that could help the agricultural community age successfully. The project recently obtained funding as an Emerging Issues Short-Term Project from the High Plains Intermountain Center for Agricultural Health and Safety.

The Department of Human Development and Family Studies is part of CSU's College of Health and Human Sciences.

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Agencies
April 15,2020

Dear parents, if you want your children to have proper sleep, read this carefully. Joining a growing list of studies that tell parents to shun devices at bed-time, researchers say that children who use devices and decide what time they go to sleep, achieve less sleep and feel more sleepier the following day than their peers.

The study of children in this age-group (aged 11 to 13 years), published in the New Zealand Medical Journal, found most (72 per cent) of the 163 students interviewed by University of Otago researchers achieved recommended guidelines of an average 9 to 11 hours sleep nightly over one week.

"But that also means that almost one in four students did not achieve sleep within these guidelines, which highlights an area for improvement," said study researcher Kate Ford.

However, consistent with previous research in 15 to 17-year-old New Zealanders, the study results show less sleep on the nights where devices are used in the hour before bed.

According to the researchers, students who used devices before going to sleep were also more likely to report that they felt sleepy the following morning. Watching television before bed had no significant effect on sleep length.

There were also some interesting observations over the weekends where students went to bed later but woke later achieving similar sleep length to the school days, the researchers said.

A small group of students (six per cent) who reported less than seven hours of sleep, including a small number reporting not sleeping at all, according to the study,

Therefore, while the average across the week of 72 per cent of students reporting adequate sleep is reassuring, it is far from the goal of every child achieving sleep within the recommended guidelines," Ford said.

Dr Paul Kelly, head of the Sleep Health Service at Canterbury District Health Board, supervised the study and explained that the foundations for good health are based on proper nutrition, regular exercise and good sleep quality.

Sleep quality is often overlooked as a contributory factor to poor health.

"The study findings suggest the need for parental guidance around bedtimings and moderation of the use and availability of electronic devices before bed," Kelly said.

"Respect and protect your sleep, as good daytime functioning is reliant on adequate sleep," Kelly added.

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