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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News Network
May 13,2020

California, May 13: A fasting-mimicking diet could be more effective at treating some types of cancer when combined with vitamin C, suggests a new study conducted by the scientists from USC and the IFOM Cancer Institute in Milan.

In studies on mice, researchers found that the combination delayed tumour progression in multiple mouse models of colorectal cancer; in some mice, it caused disease regression. The results were published in the journal Nature Communications.

"For the first time, we have demonstrated how a completely non-toxic intervention can effectively treat an aggressive cancer," said Valter Longo, the study senior author and the director of the USC Longevity Institute at the USC Leonard Davis School of Gerontology and professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences.

"We have taken two treatments that are studied extensively as interventions to delay ageing-- a fasting-mimicking diet and vitamin C -- and combined them as a powerful treatment for cancer," added Longo.

The researchers said that while fasting remains a challenging option for cancer patients, a safer, more feasible option is a low-calorie, plant-based diet that causes cells to respond as if the body were fasting.

Their findings suggest that a low-toxicity treatment of fasting-mimicking diet plus vitamin C has the potential to replace more toxic treatments.

Results of prior research on the cancer-fighting potential of vitamin C have been mixed. Recent studies, though, are beginning to show some efficacy, especially in combination with chemotherapy.

In this new study, the research team wanted to find out whether a fasting-mimicking diet could enhance the high-dose vitamin C tumour-fighting action by creating an environment that would be unsustainable for cancer cells but still safe for normal cells.

"Our first in vitro experiment showed remarkable effects. When used alone, fasting-mimicking diet or vitamin C alone reduced cancer cell growth and caused a minor increase in cancer cell death. But when used together, they had a dramatic effect, killing almost all cancerous cells," said Longo.

Longo and his colleagues detected this strong effect only in cancer cells that had a mutation that is regarded as one of the most challenging targets in cancer research.

These mutations in the KRAS gene signal the body is resisting most cancer-fighting treatments, and they reduce a patient's survival rate. KRAS mutations occur in approximately a quarter of all human cancers and are estimated to occur in up to half of all colorectal cancers.

The study also provided clues about why previous studies of vitamin C as a potential anticancer therapy showed limited efficacy. By itself, a vitamin C treatment appears to trigger the KRAS-mutated cells to protect cancer cells by increasing levels of ferritin, a protein that binds iron.

But by reducing levels of ferritin, the scientists managed to increase vitamin C's toxicity for the cancer cells. Amid this finding, the scientists also discovered that colorectal cancer patients with high levels of the iron-binding protein have a lower chance of survival.

"In this study, we observed how fasting-mimicking diet cycles are able to increase the effect of pharmacological doses of vitamin C against KRAS-mutated cancers," said Maira Di Tano, a study co-author at the IFOM, FIRC Institute of Molecular Oncology in Milan, Italy.

"This occurs through the regulation of the levels of iron and of the molecular mechanisms involved in oxidative stress. The results particularly pointed to a gene that regulates iron levels: heme-oxygenase-1," added Tano.

The research team's prior studies showed that fasting and a fasting-mimicking diet slow cancer's progression and make chemotherapy more effective in tumour cells while protecting normal cells from chemotherapy-associated side effects. The combination enhances the immune system's anti-tumour response in breast cancer and melanoma mouse models.

The scientists believe cancer will eventually be treated with low-toxicity drugs in a manner similar to how antibiotics are used to treat infections that kill particular bacteria, but which can be substituted by other drugs if the first is not effective.

To move toward that goal, they say they needed to first test two hypotheses: that their non-toxic combination interventions would work in mice, and that it would look promising for human clinical trials.

In this new study, they said that they've demonstrated both. At least five clinical trials, including one at USC on breast cancer and prostate cancer patients, are now investigating the effects of the fasting-mimicking diets in combination with different cancer-fighting drugs.

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Agencies
March 15,2020

Should you let your babies "cry it out" or rush to their side? Researchers have found that leaving an infant to 'cry it out' from birth up to 18 months does not adversely affect their behaviour development or attachment.

The study, published in the Journal of Child Psychology and Psychiatry, found that an infant's development and attachment to their parents is not affected by being left to "cry it out" and can actually decrease the amount of crying and duration.

"Only two previous studies nearly 50 or 20 years ago had investigated whether letting babies 'cry it out' affects babies' development. Our study documents contemporary parenting in the UK and the different approaches to crying used," said the study's researcher Ayten Bilgin from the University of Warwick in the UK.

For the study, the researchers followed 178 infants and their mums over 18 months and repeatedly assessed whether parents intervened immediately when a baby cried or let the baby let it cry out a few times or often.

They found that it made little difference to the baby’s development by 18 months.

The use of parent’s leaving their baby to ‘cry it out’ was assessed via maternal report at term, 3, 6 and 18 months and cry duration at term, 3 and 18 months.

Duration and frequency of fussing and crying was assessed at the same ages with the Crying Pattern Questionnaire.

According to the researchers, how sensitive the mother is in interaction with their baby was video-recorded and rated at 3 and 18 months of age.

Attachment was assessed at 18 months using a gold standard experimental procedure, the strange situation test, which assesses how securely an infant is attached to the major caregiver during separation and reunion episodes.

Behavioural development was assessed by direct observation in play with the mother and during assessment by a psychologist and a parent-report questionnaire at 18 months.

Researchers found that whether contemporary parents respond immediately or leave their infant to cry it out a few times to often makes no difference on the short - or longer term relationship with the mother or the infants behaviour.

This study shows that 2/3 of mum's parent intuitively and learn from their infant, meaning they intervene when they were just born immediately, but as they get older the mother waits a bit to see whether the baby can calm themselves, so babies learn self-regulation.

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Agencies
January 5,2020

Washington D.C., Jan 5: After a woman filed a lawsuit against a diet soda company, the California court has declared that the beverage does not promise to help buyers in losing weight.

The woman had gulped down the drink for over a decade but did not lose inches as a result.

The three-judge panel declared during the hearing: "The prevalent understanding of the term in (the marketplace) is that the 'diet' version of a soft drink has fewer calories than its 'regular' counterpart."

However, the members of the US 9th circuit court have felt that the consumers tend to make out something of their own that is unreasonable and eventually hamper the reputation of brands through a deceptive allegation, reports Fox News.

The response was due to a misleading case filed against Diet Dr Pepper by Shana Becerra from Santa Rosa, California. Shana claimed that she has been addictively purchasing the low-calorie beverage for the past 13 years hoping for losing some fat but failed to lose even a single inch.

The woman also stated that the attractive and fit models misled her into believing that drink will help her in perfecting her body like them.

However, the court's decision was that advertisements are for representational purposes only. "Cannot be reasonably understood to convey any specific meaning at all," as written by Judge Jay Bybee.

Shana had last week made such allegation against Diet coke as well where the court came to a similar verdict. She claimed that she had found various studies where it is evident that the artificial sweetener aspartame used in diet beverages actually boosts weight gain.

But the artificial sweetener is approved in by the concerned administrative department and thus is used in most American drinks.

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