A group of neurons are found to function as a “sleep switch” in the brain

From the FMS Global News Desk of Jeanne Hambleton  Embargo expired: 20-Aug-2014 Citations Brain    Source Newsroom: University of Toronto


Newswise — TORONTO, ON – As people grow older, they often have difficulty falling asleep and staying asleep, and tend to awaken too early in the morning. In individuals with Alzheimer’s disease, this common and troubling symptom of aging tends to be especially pronounced, often leading to nighttime confusion and wandering.

Now, a study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) and the University of Toronto/Sunnybrook Health Sciences Center helps explain why sleep becomes more fragmented with age. Reported online today in the journal Brain, the new findings demonstrate for the first time that a group of inhibitory neurons, whose loss leads to sleep disruption in experimental animals, are substantially diminished among the elderly and individuals with Alzheimer’s disease, and that this, in turn, is accompanied by sleep disruption.

“On average, a person in his 70s has about one hour less sleep per night than a person in his 20s,” explains senior author Clifford B. Saper, MD, PhD, Chairman of Neurology at BIDMC and James Jackson Putnam Professor of Neurology at Harvard Medical School.

“Sleep loss and sleep fragmentation is associated with a number of health issues, including cognitive dysfunction, increased blood pressure and vascular disease, and a tendency to develop type 2 diabetes. It now appears that loss of these neurons may be contributing to these various disorders as people age.”

In 1996, the Saper lab first discovered that the ventrolateral preoptic nucleus, a key cell group of inhibitory neurons, was functioning as a “sleep switch” in rats, turning off the brain’s arousal systems to enable animals to fall asleep.

“Our experiments in animals showed that loss of these neurons produced profound insomnia, with animals sleeping only about 50 percent as much as normal and their remaining sleep being fragmented and disrupted,” he explains.

A group of cells in the human brain, the intermediate nucleus, is located in a similar location and has the same inhibitory neurotransmitter, galanin, as the vetrolateral preoptic nucleus in rats. The authors hypothesized that if the intermediate nucleus was important for human sleep and was homologous to the animal’s ventrolateral preoptic nucleus, then it may also similarly regulate humans’ sleep-wake cycles.

In order to test this hypothesis, the investigators analyzed data from the Rush Memory and Aging Project, a community-based study of aging and dementia which began in 1997 and has been following a group of almost 1,000 subjects who entered the study as healthy 65-year-olds and are followed until their deaths, at which point their brains are donated for research.

“Since 2005, most of the subjects in the Memory and Aging Project have been undergoing actigraphic recording every two years. This consists of their wearing a small wristwatch-type device on their non-dominant arm for seven to 10 days,” explains first author Andrew S. P. Lim, MD, of the University of Toronto and Sunnybrook Health Sciences Center and formerly a member of the Saper lab. The actigraphy device, which is waterproof, is worn 24 hours a day and thereby monitors all movements, large and small, divided into 15-second intervals. “Our previous work had determined that these actigraphic recordings are a good measure of the amount and quality of sleep,” adds Lim.

The authors examined the brains of 45 study subjects (median age at death, 89.2), identifying ventrolateral preoptic neurons by staining the brains for the neurotransmitter galanin. They then correlated the actigraphic rest-activity behavior of the 45 individuals in the year prior to their deaths with the number of remaining ventrolateral preoptic neurons at autopsy.

“We found that in the older patients who did not have Alzheimer’s disease, the number of ventrolateral preoptic neurons correlated inversely with the amount of sleep fragmentation,” says Saper.

“The fewer the neurons, the more fragmented the sleep became.” The subjects with the largest amount of neurons (greater than 6,000) spent 50 percent or more of total rest time in the prolonged periods of non-movement most likely to represent sleep while subjects with the fewest ventrolateral preoptic neurons (less than 3,000) spent less than 40 percent of total rest time in extended periods of rest. The results further showed that among Alzheimer’s patients, most sleep impairment seemed to be related to the number of ventrolateral preoptic neurons that had been lost.

“These findings provide the first evidence that the ventrolateral preoptic nucleus in humans probably plays a key role in causing sleep, and functions in a similar way to other species that have been studied,” says Saper.

“The loss of these neurons with aging and with Alzheimer’s disease may be an important reason why older individuals often face sleep disruptions. These results may, therefore, lead to new methods to diminish sleep problems in the elderly and prevent sleep-deprivation-related cognitive decline in people with dementia.”

Co-authors include first author Andrew S. P. Lim of BIDMC and the University of Toronto and BIDMC investigators Brian A Ellison and Joshua L. Wang; and Rush University investigators Lei Yu, Julie A. Schneider, Aron S. Buchman and David A. Bennett.



From the FMS Global News Desk of Jeanne HambletonReleased: 20-Aug-2014                    Journal of Neuroscience  Source Newsroom: Seattle Children’s Hospital

Newswise — Scientists at Seattle Children’s Research Institute have discovered an area of the brain that could control a person’s motivation to exercise and participate in other rewarding activities – potentially leading to improved treatments for depression.

Dr. Eric Turner, a principal investigator in Seattle Children’s Research Institute’s Center for Integrative Brain Research, together with lead author Dr. Yun-Wei (Toni) Hsu, have discovered that a tiny region of the brain – the dorsal medial habenula – controls the desire to exercise in mice. The structure of the habenula is similar in humans and rodents and these basic functions in mood regulation and motivation are likely to be the same across species.

Exercise is one of the most effective non-pharmacological therapies for depression. Determining that such a specific area of the brain may be responsible for motivation to exercise could help researchers develop more targeted, effective treatments for depression.

“Changes in physical activity and the inability to enjoy rewarding or pleasurable experiences are two hallmarks of major depression,” Turner said

“But the brain pathways responsible for exercise motivation have not been well understood. Now, we can seek ways to manipulate activity within this specific area of the brain without impacting the rest of the brain’s activity.”

Dr. Turner’s study, titled “Role of the Dorsal Medial Habenula in the Regulation of Voluntary Activity, Motor Function, Hedonic State, and Primary Reinforcement,” was published today by the Journal of Neuroscience and funded by the National Institute of Mental Health and National Institute on Drug Abuse. The study used mouse models that were genetically engineered to block signals from the dorsal medial habenula. In the first part of the study, Dr. Turner’s team collaborated with Dr. Horacio de la Iglesia, a professor in University of Washington’s Department of Biology, to show that compared to typical mice, who love to run in their exercise wheels, the genetically engineered mice were lethargic and ran far less. Turner’s genetically engineered mice also lost their preference for sweetened drinking water.

“Without a functioning dorsal medial habenula, the mice became couch potatoes,” Turner said.“They were physically capable of running but appeared unmotivated to do it.
In a second group of mice, Dr. Turner’s team activated the dorsal medial habenula using optogenetics – a precise laser technology developed in collaboration with the Allen Institute for Brain Science. The mice could “choose” to activate this area of the brain by turning one of two response wheels with their paws. The mice strongly preferred turning the wheel that stimulated the dorsal medial habenula, demonstrating that this area of the brain is tied to rewarding behavior.

Past studies have attributed many different functions to the habenula, but technology was not advanced enough to determine roles of the various subsections of this area of the brain, including the dorsal medial habenula.

“Traditional methods of stimulation could not isolate this part of the brain,” Turner said. “But cutting-edge technology at Seattle Children’s Research Institute makes discoveries like this possible.”

As a professor in the University of Washington Department of Psychiatry and Behavioral Sciences, Dr. Turner treats depression and hopes this research will make a difference in the lives of future patients.

“Working in mental health can be frustrating,” Turner said. “We have not made a lot of progress in developing new treatments. I hope the more we can learn about how the brain functions the more we can help people with all kinds of mental illness.”

About Seattle Children’s Research Institute
Located in downtown Seattle’s biotech corridor, Seattle Children’s Research Institute is pushing the boundaries of medical research to find cures for pediatric diseases and improve outcomes for children all over the world. Internationally recognized investigators and staff at the research institute are advancing new discoveries in cancer, genetics, immunology, pathology, infectious disease, injury prevention and bioethics, among others. As part of Seattle Children’s Hospital, the research institute brings together leading minds in pediatric research to provide patients with the best care possible. Seattle Children’s serves as the primary teaching, clinical and research site for the Department of Pediatrics at the University of Washington School of Medicine, which consistently ranks as one of the best pediatric departments in the country.



From the FMS Global News Desk of Jeanne Hambleton                                                               PULSE 19 August 2014         By Caroline Price


GPs feel pressure to prescribe antibiotics and sometimes prescribe them even when they do not feel it is necessary, a survey has revealed.

The survey of 1,000 GPs found 90% of respondents felt pressure from patients to prescribe them antibiotics, while over a quarter – 28% – said they prescribe them several times a week when they are unsure they are medically necessary.

The survey was commissioned by charity Nesta for the £10 million Longitude Prize – after the public voted for the prize to be focused on antibiotic use and the growing problem of antibiotic resistance.

Nearly half – 45% – of the GPs surveyed said they had prescribed antibiotics for a viral infection, knowing it would not be effective. But 70% of GPs also said they sometimes prescribed them because of doubts about whether an infection was viral or bacterial, with 24% citing a lack of easy-to-use diagnostic tools.

Dr Rosemary Leonard, a GP in London, said: ‘These results show the pressure GPs face to prescribe antibiotics when they are not necessary, something I understand very well.’

‘The more antibiotics taken, the more resistant bacteria come to them. Antibiotic resistance is a real issue and more needs to be done conserve antibiotics for the future. Diagnostics play a valuable role in making this happen. Not only can diagnostics help determine the type of infection someone has, they could gather valuable data and aid the global surveillance efforts.’



From the FMS Global News Desk of Jeanne Hambleton   PULSE 20 August 2014                      By Christina Kenny


The proposed closure of a GP surgery arm in Sheffield has been described by GP leaders as the possible first casualty of England-wide PMS reviews, with the local MP stepping in to demand answers from NHS England over claims that ‘half the patients in his constituency’ could be affected by cuts.

The Sothall and Beighton Medical Practice has informed its 10,000-plus patients that it stands to potentially lose £220,000 – roughly a quarter of its total funding – over a four-year period, and has invited patients to take part in a three-month consultation to decide whether to keep both arms of its surgery open but with drastically reduced services, or close the recently-refurbished Beighton Medical Centre.

NHS England’s local area team for South Yorkshire and Bassetlaw confirmed that it had informed practices of how much funding would come under review as part of plans to ensure ‘all GP practices have equitable access to funds’. It said that the process was ‘at an early stage’ but urged patients to participate in the consultation launched by the practice.

A spokesperson said: ‘Measures are being put in place to ensure funding for every GP practice is equitable and all practices have equal access to funds.’

‘Under new arrangements practices will be able to received additional funding providing they met a number of key performance indicators centred on the services they offer to their patients. We would encourage patients registered with the Sothall and Beighton GP practice to get involved in the surgery’s public consultation by filling in and sending back the relevant forms.’

‘NHS England in South Yorkshire and Bassetlaw is committed to ensuring patients have access to the best primary care services available and that patients everywhere have equal access to high quality services.’

But Sothall and Beighton Medical Practice’s manager, Jackie Ashton, told Pulse it was likely that there would be a significant reduction in clinical appointments whether or not both surgeries remained open.

She added: ‘We feel that this is likely to be more dramatic if we have to keep both sites operational.’

‘Predictably, patients who live closest to the Beighton Health Centre and would likely be more profoundly affected have argued for this site to remain open and we have encouraged them to present their views to their MP and councillors as well as completing our questionnaire.’

Labour MP for Sheffield South East Clive Betts told Pulse he has written to commissioners demanding information on how many GP practices were affected and how much total funding is at stake, but that he is waiting for a response.

Mr Betts said: ‘I am pretty angry about it. GP practices are already struggling – I have had more complaints about problems getting doctors’ appointments in the last year than I have ever had.’

‘We are supposed to be trying to increase the level of services delivered at primary level and reducing the pressure on acute beds in hospitals, and keeping people in the community because it is better for them and more cost-effective. How can you do that if you cut GP funding? It is completely counter-productive.’

GPC deputy chair Dr Richard Vautrey said that the proposed closure was ‘the first very clear example of the impact of the PMS review that I have come across’.

He added: ‘I anticipate it will be the first of many. The amount of money being cut from PMS practices is three times as much as the amount being recycled from correction factors payments for GMS practices.’

‘I think there are huge concerns that this is going to have a massive impact right around the country. Practices are starting to be told how much they are going to be losing, and some practices stand to lose massive amounts of money in a very short space of time.’

GP leaders have warned of ‘illogical’ variety of approaches by area teams to the PMS reviews that have been centrally decreed by NHS England, with some area teams offering support to pratices switching to GMS and other not. Meanwhile, London PMS practices are set to be paid based on a set of ‘outcomes standards’ which could include cancer survival rates and A&E attendances. In some areas, accountants have warned that practices were facing losses of up to £400,000 which would also leave them unviable.

Where will it all end I wonder? Back tomorrow Jeanne






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