Brain's on-off thirst switch identified

January 27, 2015

Brains on-off

Washington, Jan 27: Scientists have identified neurons that trigger our sense of thirst and those that turn it off.

For years, researchers have suspected that thirst is regulated by neurons in the subfornical organ (SFO), in the hypothalamus. But it has been difficult to pinpoint exactly which neurons are involved.

“When researchers used electrical current to stimulate different parts of the SFO of mice, they got confusing results,” said lead author Yuki Oka, a postdoctoral research scientist in the laboratory of Charles S Zuker, a Howard Hughes Medical Institute Investigator at Columbia University Medical Center (CUMC).

The CUMC team hypothesised that there are at least two types of neurons in the SFO, including ones that drive thirst and others that suppress it.

“Those electrostimulation experiments were probably activating both types of neurons at once, so they were bound to get conflicting results,” said Oka.

To test their hypothesis, Oka and Zuker turned to optogenetics, a more precise technique for controlling brain activity. With optogenetics, researchers can control specific sets of neurons in the brain after inserting light-activated molecules into them.

Shining light onto these molecules turns on the neurons without affecting other types of neurons nearby.

These “mind-control” experiments revealed two types of neurons in the SFO that control thirst: CAMKII neurons, which turn thirst on, and VGAT neurons, which turn it off.

When the researchers turned on CAMK11 neurons, mice immediately began to seek water and to drink intensively.

This behaviour was as strong in well-hydrated mice as in dehydrated ones. Once the neurons were shut off – by turning off the light – the mice immediately stopped drinking.

The researchers also found that light-stimulation of the CAMKII neurons did not induce feeding behaviour. In addition, light-induced thirst was specific for water and did not increase the animals’ consumption of other fluids, including glycerol and honey.

Similar experiments with VGAT neurons showed that these neurons act to turn off thirst. When the researchers turned on these neurons with light, dehydrated mice immediately stopped drinking, even if they were drinking water.

“Together, these findings show that the SFO is a dedicated brain system for thirst,” said Oka.

“The SFO is one of few neurological structures that is not blocked by the blood-brain barrier – it’s completely exposed to the general circulation,” said Oka.

“This raises the possibility that it may be possible to develop drugs for conditions related to thirst,” Oka added.

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Agencies
May 8,2020

As Europe and the US loosen their lockdowns against the coronavirus, health experts are expressing growing dread over what they say is an all-but-certain second wave of deaths and infections that could force governments to clamp back down.

"We are risking a backslide that will be intolerable," said Dr Ian Lipkin of Columbia University's Center for Infection and Immunity.

Around the world, German authorities began drawing up plans in case of a resurgence of the virus. Experts in Italy urged intensified efforts to identify new victims and trace their contacts. And France, which has not yet eased its lockdown, has already worked up a "reconfinement plan" in the event of a new wave.

"There will be a second wave, but the problem is to which extent. Is it a small wave or a big wave? It is too early to say," said Olivier Schwartz, head of the virus unit at France's Pasteur Institute.

In the US, with about half of the states easing their shutdowns to get their economies restarted and cellphone data showing that people are becoming restless and increasingly leaving home, public health authorities are worried.

Many states have not put in place the robust testing that experts believe is necessary to detect and contain new outbreaks. And many governors have pressed ahead before their states met one of the key benchmarks in the Trump administration's guidelines for reopening -- a 14-day downward trajectory in new illnesses and infections.

"If we relax these measures without having the proper public health safeguards in place, we can expect many more cases and, unfortunately, more deaths," said Josh Michaud, associate director of global health policy with the Kaiser Family Foundation in Washington.

Cases have continued to rise steadily in places such as Iowa and Missouri since the governors began reopening, while new infections have yo-yoed in Georgia, Tennessee and Texas.

Lipkin said he is most worried about two things: the reopening of bars, where people crowd together and lose their inhibitions, and large gatherings such as sporting events, concerts and plays. Preventing outbreaks will require aggressive contact tracing powered by armies of public health workers hundreds of thousands of people strong, which the US does not yet have, Lipkin said.

Worldwide the virus has infected more than 36 lakh people and killed over a quarter-million, according to a tally by Johns Hopkins University that experts agree understates the dimensions of the disaster because of limited testing, differences in counting the dead and concealment by some governments.

The US has recorded over 70,000 deaths and 12 lakh confirmed infections, while Europe has reported over 140,000 dead.

This week, the researchers behind a widely cited model from the University of Washington nearly doubled their projection of deaths in the US to around 134,000 through early August, in large part because of the easing of state stay-at-home restrictions. Newly confirmed infections per day in the US exceed 20,000 and deaths per day are running well over 1,000.

In hard-hit New York City, which has managed to bring down deaths dramatically even as confirmed infections continue to rise around the rest of the country, Mayor Bill de Blasio warned that some states may be reopening too quickly.

"My message to the rest of the country is learn from how much effort, how much discipline it took to finally bring these numbers down and follow the same path until you are sure that it is being beaten back," he said on CNN, "or else, if this thing boomerangs, you are putting off any kind of restart or recovery a hell of a lot longer."

A century ago, the Spanish flu epidemic's second wave was far deadlier than its first, in part because authorities allowed mass gatherings from Philadelphia to San Francisco.

"It is clear to me that we are in a critical moment of this fight. We risk complacency and accepting the preventable deaths of 2,000 Americans each day," epidemiologist Caitlin Rivers, a professor at Johns Hopkins, told a House subcommittee in Washington.

President Donald Trump, who has pressed hard to ease the restrictions that have throttled the economy and thrown more than three crore Americans out of work, pulled back Wednesday on White House plans revealed a day earlier to wind down the coronavirus task force.

He tweeted that the task force will continue meeting indefinitely with a "focus on SAFETY & OPENING UP OUR COUNTRY AGAIN".

Underscoring those economic concerns, the European Union predicted the worst recession in its quarter-century history. And the US unemployment rate for April, which comes out on Friday, is expected to hit a staggering 16 per cent, a level last seen during the Great Depression of the 1930s.

Governors continue to face demands, even lawsuits, to reopen. In Michigan, where armed demonstrators entered the Capitol last week, the Republican-led Legislature sued Democratic Governor Gretchen Whitmer, asking a judge to declare invalid her stay-at-home order, which runs at least through May 15.

In hard-hit Italy, which has begun easing restrictions, Dr Silvio Brusaferro, president of the Superior Institute of Health, urged "a huge investment" of resources to train medical personnel to monitor possible new cases of the virus, which has killed about 30,000 people nationwide.

He said that contact-tracing apps which are being built by dozens of countries and companies are not enough to manage future waves of infection.

German Chancellor Angela Merkel said after meeting with the country's 16 governors that restaurants and other businesses will be allowed to reopen in the coming weeks but that regional authorities will have to draw up a "restriction concept" for any county that reports 50 new cases for every 100,000 inhabitants within a week.

Lothar Wieler, head of Germany's national disease control centre, said scientists "know with great certainty that there will be a second wave" of infections.

Britain, with over 30,000 dead, the second-highest death toll in the world behind the US, plans to extend its lockdown but has begun recruiting 18,000 people to trace contacts of those infected.

In other developments, the US Centers for Disease Control and Prevention said nearly 5,000 coronavirus illnesses and at least 88 deaths have been reported among inmates in American jails and prisons. An additional 2,800 cases and 15 deaths were reported among guards and other staff members.

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Agencies
May 19,2020

Researchers have found that patients with peripheral artery disease or stroke were less likely to receive recommended treatments to prevent heart attack than those with coronary artery disease. All three are types of atherosclerotic cardiovascular disease.

Depending on the location of the blockage, atherosclerosis increases the risk for three serious conditions: coronary artery disease, stroke and peripheral artery disease.

"Our study highlights the need for public health campaigns to direct equal attention to all three major forms of atherosclerotic cardiovascular disease," said senior study author Erin Michos from the Johns Hopkins University in the US.

"We need to generate awareness among both clinicians and patients that all of these diseases should be treated with aggressive secondary preventive medications, including aspirin and statins, regardless of whether people have heart disease or not," Michos added.

Since atherosclerosis can affect arteries in more than one part of the body, medical guidelines are to treat coronary artery disease, stroke and peripheral artery disease similarly with lifestyle changes and medication, including statins to lower cholesterol levels and aspirin to prevent blood clots.

Lifestyle changes include eating a healthy diet, being physically active, quitting smoking, controlling high cholesterol, controlling high blood pressure, treating high blood sugar and losing weight.

What was unclear was if people with stroke and peripheral artery disease received the same treatments prescribed for those with coronary artery disease.

This study compared more than 14,000 US adults enrolled in the 2006-2015 Medical Expenditure Panel Survey, a national survey of patient-reported health outcomes and conditions, and health care use and expenses.

Slightly more than half of the patients were men, the average age was 65, and all had either coronary artery disease, stroke or peripheral artery disease.

These individuals were the representative of nearly 16 million US adults living with one of the three forms of atherosclerotic cardiovascular disease.

Compared to participants with coronary artery disease, participants with peripheral artery disease were twice more likely to report no statin use and three times more likely to report no aspirin use.

Additionally, people with peripheral artery disease had the highest, annual, total out-of-pocket expenditures among the three atherosclerotic conditions.

The findings showed that participants with stroke were more than twice as likely to report no statin or aspirin use.

Moreover, those with stroke were more likely to report poor patient-provider communication, poor health care satisfaction and more emergency room visits.

"Our study highlights a missed opportunity for implementing life-saving preventive medications among these high-risk individuals," Michos said.

The study was presented in the virtual conference at the American Heart Association's Quality of Care & Outcomes Research Scientific Sessions 2020.

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Agencies
March 16,2020

New Delhi, Mar 16: A recent survey across 140 districts of the country shows that about 54 per cent of Indians are finding travelling to be unsafe as the deadly coronavirus (COVID-19) pandemic sweeps globally.

The big worry that people have is community transmission, something that researchers from around the world have approximated at 10 per cent of total infections and more common in places like Wuhan in China, South Korea, Iran and Italy.

The months of March to June have historically been high travel season for most Indians, largely due to the summer vacations in schools. "But it seems that Indians do not want to take a chance with this rather scary virus and are either cancelling or postponing their travel plans," concluded the survey by LocalCircles.

The survey gathered more than 22,000 responses from participants in tier one, two and three cities. It said 48 per cent Indians plan to cancel their international business travel for the next four months.

Besides, nearly 38 per cent of respondents said they had to pay cancellation fee to the website, travel agent, airline or railways.

"These are testing times for the entire travel and tourism industry -- airlines, hotels, travel agents as well as small tour and taxi operators. The best solution at this point is to adjust cost structures, stay flexible and work with a collective approach to minimise the period of impact to both citizens and business," said LocalCircles.

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