Home

New key player in long-term memory

A McGill-led multi-institutional research team has discovered that during memory consolidation, there are at least two distinct processes taking place in two different brain networks -- the excitatory and inhibitory networks. The excitatory neurons are involved in creating a memory trace, and the inhibitory neurons block out background noise and allow long-term learning to take place.

The team, led by McGill University Professors Nahum Sonenberg and Arkady Khoutorsky, Université de Montréal Professor Jean-Claude Lacaille, and University of Haifa Professor Kobi Rosenblum, senior authors on the paper published today in Nature, also found that each neuronal system can be selectively manipulated to control long-term memory. The research, which answers a long-standing question about which neuronal subtypes are involved in memory consolidation, has potential implications for novel targets for medication for disorders such as Alzheimer's disease and autism, which involve altered memory processes.

Looking for the neurons involved in memory consolidation

How do short-term memories (which last just a few hours) transform into long-term memories (which may last years)? It's been known for decades that this process, called memory consolidation, requires the synthesis of new proteins in brain cells. But until now, it hasn't been known which subtypes of neurons were involved in the process.

To identify which neuronal networks are essential in memory consolidation, the researchers used transgenic mice to manipulate a particular molecular pathway, eIF2α, in specific types of neurons. This pathway had already been shown to play a key role in controlling the formation of long-term memories and regulating protein synthesis in neurons. Moreover, earlier research had identified eIF2α as pivotal for both neurodevelopmental and neurodegenerative diseases.

Excitatory and inhibitory systems both play a role in memory consolidation

"We found that stimulation of protein synthesis via eIF2α in excitatory neurons of the hippocampus was sufficient to enhance memory formation and modification of synapses, the sites of communication between neurons," says Dr. Kobi Rosenblum.

However, interestingly, "we also found that stimulation of protein synthesis via eIF2α in a specific class of inhibitory neurons, somatostatin interneurons, was also sufficient to augment long-term memory by tuning the plasticity of neuronal connections," says Dr. Jean-Claude Lacaille.

"It is fascinating to be able to show that these new players -- inhibitory neurons -- have an important role in memory consolidation," added Dr. Vijendra Sharma, a research associate in Prof. Sonenberg's lab and the first author on the paper. "It had been assumed, until now, that eIF2α pathway regulates memory via excitatory neurons."

"These new findings identify protein synthesis in inhibitory neurons, and specifically somatostatin cells, as a novel target for possible therapeutic interventions in disorders such as Alzheimer's disease and autism," concluded Dr. Nahum Sonenberg. "We hope that this will help in the design of both preventative and post-diagnosis treatments for those who suffer from disorders involving memory deficits."

The research was funded by: Canada's International Development Research Centre (IDRC), in partnership with the Azrieli Foundation, the Canadian Institutes of Health Research (CIHR), and the Israel Science Foundation (ISF) to K.R. and N.S., JCL is supported by a CIHR Project grant and a Canada Research Chair in Cellular and Molecular Neurophysiology.

Story Source:

Materials provided by McGill University. Note: Content may be edited for style and length.

https://www.sciencedaily.com/releases/2020/10/201007123121.htm

Journal Reference:

Vijendra Sharma, Rapita Sood, Abdessattar Khlaifia, Mohammad Javad Eslamizade, Tzu-Yu Hung, Danning Lou, Azam Asgarihafshejani, Maya Lalzar, Stephen J. Kiniry, Matthew P. Stokes, Noah Cohen, Alissa J. Nelson, Kathryn Abell, Anthony P. Possemato, Shunit Gal-Ben-Ari, Vinh T. Truong, Peng Wang, Adonis Yiannakas, Fatemeh Saffarzadeh, A. Claudio Cuello, Karim Nader, Randal J. Kaufman, Mauro Costa-Mattioli, Pavel V. Baranov, Albert Quintana, Elisenda Sanz, Arkady Khoutorsky, Jean-Claude Lacaille, Kobi Rosenblum, Nahum Sonenberg. eIF2α controls memory consolidation via excitatory and somatostatin neurons. Nature, 2020; DOI: 10.1038/s41586-020-2805-8

Heartburn Meds Tied to Higher Diabetes Risk

Often-used drugs called proton pump inhibitors (PPIs) ease heartburn symptoms, but a new study suggests they might also increase the risk of type 2 diabetes.

Chinese researchers drew on information from studies of more than 200,000 U.S. health care professionals and found that regular use of PPIs (such as Aciphex, Nexium, Prilosec, Prevacid, Protonix) was associated with a 24% higher risk of developing type 2 diabetes.

The researchers also found that the longer people used the drugs, the higher their odds of diabetes.

"Regular PPI use was likely to be associated with an increased risk of type 2 diabetes, particularly for those with prolonged use," the authors wrote in the report published online Sept. 28 in the journal Gut.

Jinqiu Yuan, a researcher from the Sun Yat-Sen University, Shenzhen, Guangdong, China, led the study.

PPIs are available by prescription or over-the-counter to treat acid reflux, peptic ulcers and other digestive conditions. They are among the top 10 drugs used worldwide. Long-term use has previously been linked to a greater risk of bone fractures, kidney disease, digestive tract infections and stomach cancer.

Based on the new findings, the researchers suggested that people taking PPIs for a long time should have their blood sugar monitored for changes that might indicate developing diabetes.

It's important to note, however, that this study was not designed to prove a cause-and-effect relationship between PPIs and type 2 diabetes. It can only show a link between the two.

The researchers relied on data from three long-term studies of U.S. health professionals that began in the 1970s and 1980s. They included more than 176,000 women and nearly 29,000 men.

Participants provided information on their health and behaviors every two years. In the early 2000s, the questions expanded to include whether they had used a PPI two or more times a week.

The investigators tried to control for factors that might affect type 2 diabetes risk, including high blood pressure, weight and physical inactivity.

Besides linking regular use of PPIs to an increased risk of type 2 diabetes, the researchers found that long-term use increased the odds, too. Study participants who used PPIs for up to two years had a 5% increased risk, and the risk rose 26% for those who took the drugs more than two years.

The study authors also noted that when people stopped taking these drugs, the risk of diabetes fell, and it continued to do so even more over time.

Surprisingly, the risk of diabetes associated with PPI use appeared to be highest in people with normal blood pressure and lower weight. Typically, higher weight is a risk factor for type 2 diabetes.

The study also found a 14% higher risk of type 2 diabetes in people taking another type of heartburn medication called H2 receptor blockers (such as Pepcid, Tagamet, Zantac).

It's unclear exactly how taking acid-reducing medications might increase diabetes risk, the researchers said. One possible way might be through altering the body's natural balance of bacteria (microbiome), they suggested. Another possibility: PPI use may lead to weight gain that can increase the odds of diabetes. More research is needed.

Dr. David Bernstein, a digestive disease specialist from Northwell Health in Manhasset, N.Y., reviewed the findings.

"PPIs are the most effective therapies for the treatment of acid reflux, gastritis and peptic ulcers," Bernstein said. "When first introduced, they were considered 'miracle' drugs as they alleviated previously refractory abdominal pains."

Unfortunately, as the study authors noted, these drugs have been linked to some serious long-term side effects.

"This report, despite its weaknesses, adds yet another potential consequence to an already growing list of medical conditions associated with long-term PPI use," Bernstein said. Weaknesses included the observational nature of the study and lack of randomized comparison groups, he noted.

Still, based upon the findings, it seems reasonable to check patients who have been taking PPIs for more than two years for development of diabetes at regular intervals, he said. "Further studies are required to determine what that interval should be," Bernstein explained.

Another digestive disease specialist, Dr. Arun Swaminath, from Lenox Hill Hospital in New York City, agreed that the study had limitations.

"The main limitation of the study is that the true estimation of PPI exposure is based on memory and recall bias," he said.

But, due to this study's findings and other associated risks of long-term PPI use, Swaminath said, "it's reasonable to always see if a patient still needs their PPI" or if their dose could be lowered.

For those who need to stay on PPIs, doctors and patients need to discuss the drugs' risks and benefits, he advised. Because PPIs are available over-the-counter, "it will not be a simple process to identify all at-risk patients," Swaminath pointed out. (By Serena Gordon, HealthDay Reporter)

Source:https://www.medicinenet.com/script/main/art.asp?articlekey=247429

VCO a potential antiviral agent against COVID-19 — Filipino research

Filipino experiments revealed evidence that virgin coconut oil may be a means to defeat COVID-19.

“There are still alternative solutions against COVID-19 aside from vaccines. Although further investigation is needed before we develop a possible prevention or treatment option, we aim to give Filipinos hope through our ongoing local research initiatives,” said Department of Science and Technology Secretary Fortunato de la Peña.

After six months of experiments, results showed that compounds from coconut oil and virgin coconut oil, or VCO, a readily available commodity in the Philippines, decreased coronavirus count by 60-90% at low viral load.

Researchers also discovered that said compounds were observed to improve cell survival. More experiments, however, are needed to determine whether higher concentrations of these compounds will further reduce the replication rate of the virus.

"The results are very promising, as not only does it show that the VCO, by itself, can destroy the virus, but it also has a key mechanism in upregulating the immune response against COVID-19. Indeed, we look forward to the results of clinical trials on the various uses of VCO as an adjunct for the treatment of COVID-19," said Dr. Jaime C. Montoya, Executive Director of the Philippine Council for Health Research and Development (PCHRD).

Funded by the DOST-PCHRD, the research led by Dr. Fabian Dayrit of Ateneo De Manila University sought to investigate if coconut oil compounds are effective antiviral agents to prevent or reduce COVID-19 infection, following reports of previous research that VCO compounds are effective at killing other viruses.

With the lack of an available vaccine for COVID-19, DOST seeks to intensify the thrust for alternative solutions to the increasing cases of COVID-19 by all means supporting Filipino research and innovations. Currently, the DOST, together with the Food and Nutrition Research Institute and the University of the Philippines - Manila, is already exploring the capability of VCO to upregulate the immune system. Results from these ongoing VCO Clinical trials will determine whether VCO can be used as an adjunct therapy for COVID-19 patients.

Aside from facilitating the eventual conduct of the WHO vaccine clinical trials in the Philippines, the DOST-PCHRD is also supporting projects under its initiatives on Repurposing of Existing Drugs, Supplements, and other Formulations, and Clinical Trials of Candidate Drugs to find viable treatment options against COVID-19. (Written by Christine Jane Gonzalez)

Source: http://www.pchrd.dost.gov.ph/index.php/news/6599-vco-a-potential-antiviral-agent-against-covid-19-filipino-research

How Are Vitamin D Levels Tied to COVID-19 Risks?

Low blood levels of vitamin D might heighten people's odds for severe or even fatal COVID-19, new research shows.

Taking in a healthy level of vitamin D may therefore "reduce the complications, including the cytokine storm [release of too many proteins into the blood too quickly] and ultimately death from COVID-19," said study author Dr. Michael Holick. He's a professor of medicine, physiology, biophysics and molecular medicine at Boston University School of Medicine.

Vitamin D is called the "sunshine vitamin" because it's manufactured naturally by the skin upon contact with sunlight. But it can also be sourced through certain foods and supplements.

One respiratory health expert who wasn't involved in the study said the findings echo those of prior research.

"Several studies have brought to light that patients with vitamin D deficiency have a worse outcome in COVID-19," said pulmonologist and internist Dr. Len Horovitz, of Lenox Hill Hospital in New York City. "This is not surprising since vitamin D seems to have a beneficial effect on the immune system and wound healing."

In the new study, Holick and his colleagues assessed vitamin D levels in blood samples from 235 hospitalized COVID-19 patients. The blood samples were also checked for an inflammatory marker called C-reactive protein and for the number of lymphocytes, a type of immune cell that helps fight infection.

The study couldn't prove cause and effect. But patients who were vitamin D-sufficient -- a blood level of at least 30 nanograms per milliliter -- had a significantly lower risk for serious complications from COVID-19, including losing consciousness, low blood oxygen levels and death.

Among patients older than 40, those who were vitamin D-sufficient were also 51.5% less likely to die from COVID-19 compared to those who were vitamin D-deficient or insufficient, the team said.

The study was published Sept. 25 in the journal PLOS ONE.

A prior study by Holick found that having a sufficient amount of vitamin D might also reduce the risk of becoming infected with the new coronavirus by 54%. Along with helping reduce the risks associated with the new coronavirus, being vitamin D-sufficient does the same against other viruses that cause upper respiratory tract illnesses, including the flu, according to Holick.

"There is great concern that the combination of an influenza infection and a coronal viral infection could substantially increase hospitalizations and death due to complications from these viral infections," he said in a university news release.

All in all, vitamin D could offer a simple and cost-effective way to combat the new coronavirus, Holick believes. "Because vitamin D deficiency and insufficiency is so widespread in children and adults in the United States and worldwide, especially in the winter months, it is prudent for everyone to take a vitamin D supplement to reduce risk of being infected and having complications from COVID-19," he said.

But Horovitz noted that vitamin D might be a bit tougher to come by this year.

"During lockdown, people were indoors more and so their natural D level was lower than ever," he pointed out. "In people who don't take D, their level is usually low unless they take D as a supplement.

"I have been testing the level in all patients for years, and have found especially low levels since people have been indoors and quarantining," Horovitz said. "The dose is usually several thousand international units per day and can be tested with a blood test routinely." (By E.J. Mundell, HealthDay Reporter)

Source: https://www.medicinenet.com/script/main/art.asp?articlekey=247206

Foods, Medicines That Can Lower Colon Cancer Risk

Certain nutrients, foods, and medicines may help protect you against colon cancer, a large research review suggests.

A team of international researchers led by Dr. Marc Bardou, of Dijon Bourgogne University Hospital in France, reviewed about 80 studies that examined how diet and certain medicines affected colon cancer risk. The studies were published between September 1980 and June 2019.

In terms of medicines, aspirin (a nonsteroidal anti-inflammatory drug, or NSAID) appears to lower the risk by 14% to 29% at doses as low as 75 milligrams (mg)/day and as high as 325 mg/day.

The use of NSAIDs for up to five years was associated with a 26% to 43% reduction in incidence.

High intake of folic acid, a B vitamin, was associated with up to a 15% lower risk, although it wasn't possible to determine a minimum dose, according to findings published Sept. 28 in the journal Gut.

Similarly, eating dairy products appeared to lower risk by 13% to 19%, but the amount needed to protect against colon cancer was unclear.

Fiber intake was associated with a 22% to 43% lower risk, while fruit/vegetable consumption with as much as a 52% lower risk.

There was no evidence that vitamins E, C, multivitamins, beta carotene or selenium were protective against colon cancer, the review found.

Results on the impact of tea, garlic or onions, vitamin D either alone or combined with calcium, coffee, and caffeine, fish and omega-3 were weak or uncertain, and there were inconsistent findings on whether vitamin A and the B vitamins offered any protection.

There was conflicting data on high calcium intake and cholesterol-lowering statin drugs.

Meat, particularly red and processed meat, was associated with a 12% to 21% increased risk of colon cancer.

Alcohol also was linked to significantly higher risk. Even one or two drinks a day increased colon cancer odds, and the more people drank, the higher their risk.

In a journal news release, the researchers noted that the level of evidence of nutrients, foods and medicines providing protection against colon cancer is low or very low in most cases.

Even so, they said their findings could help doctors advise patients on the best diet to reduce bowel cancer risk and also guide future research.

Worldwide, more than 2.2 million new cases of colon cancer and 1.1 million deaths are projected annually by 2030. In the United States, colon cancer strikes about 1 in 20 people.

-- Robert Preidt

Source: https://www.medicinenet.com/script/main/art.asp?articlekey=247319