Study suggests fructose could drive Alzheimer's disease

 An ancient human foraging instinct, fueled by fructose production in the brain, may hold clues to the development and possible treatment of Alzheimer's disease (AD), according to researchers at the University of Colorado Anschutz Medical Campus.

The study, published recently in The American Journal of Clinical Nutrition, offers a new way of looking at a fatal disease characterized by abnormal accumulations of proteins in the brain that slowly erode memory and cognition.

"We make the case that Alzheimer's disease is driven by diet," said the study's lead author Richard Johnson, MD, professor at the University of Colorado School of Medicine specializing in renal disease and hypertension. The study co-authors include Maria Nagel, MD, research professor of neurology at the CU School of Medicine.

Johnson and his team suggest that AD is a harmful adaptation of an evolutionary survival pathway used in animals and our distant ancestors during times of scarcity.

"A basic tenet of life is to assure enough food, water and oxygen for survival," the study said. "Much attention has focused on the acute survival responses to hypoxia and starvation. However, nature has developed a clever way to protect animals before the crisis actually occurs."

When threatened with the possibility of starvation, early humans developed a survival response which sent them foraging for food. Yet foraging is only effective if metabolism is inhibited in various parts of the brain. Foraging requires focus, rapid assessment, impulsivity, exploratory behavior and risk taking. It is enhanced by blocking whatever gets in the way, like recent memories and attention to time. Fructose, a kind of sugar, helps damp down these centers, allowing more focus on food gathering.

In fact, the researchers found the entire foraging response was set in motion by the metabolism of fructose whether it was eaten or produced in the body. Metabolizing fructose and its byproduct, intracellular uric acid, was critical to the survival of both humans and animals.

The researchers noted that fructose reduces blood flow to the brain's cerebral cortex involved in self-control, as well as the hippocampus and thalamus. Meanwhile, blood flow increased around the visual cortex associated with food reward. All of this stimulated the foraging response.

"We believe that initially the fructose-dependent reduction in cerebral metabolism in these regions was reversible and meant to be beneficial," Johnson said. "But chronic and persistent reduction in cerebral metabolism driven by recurrent fructose metabolism leads to progressive brain atrophy and neuron loss with all of the features of AD."

Johnson suspects the survival response, what he calls the "survival switch," that helped ancient humans get through periods of scarcity, is now stuck in the "on" position in a time of relative abundance. This leads to the overeating of high fat, sugary and salty food prompting excess fructose production.

Fructose produced in the brain can lead to inflammation and ultimately Alzheimer's disease, the study said. Animals given fructose show memory lapses, a loss in the ability to navigate a maze and inflammation of the neurons.

"A study found that if you keep laboratory rats on fructose long enough they get tau and amyloid beta proteins in the brain, the same proteins seen in Alzheimer's disease," Johnson said. "You can find high fructose levels in the brains of people with Alzheimer's as well."

Johnson suspects that the tendency of some AD patients to wander off might be a vestige of the ancient foraging response.

The study said more research is needed on the role of fructose and uric acid metabolism in AD.

"We suggest that both dietary and pharmacologic trials to reduce fructose exposure or block fructose metabolism should be performed to determine if there is potential benefit in the prevention, management or treatment of this disease," Johnson said.

More information: Richard J. Johnson et al, Could Alzheimer's disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism?, The American Journal of Clinical Nutrition (2023). DOI: 10.1016/j.ajcnut.2023.01.002

https://medicalxpress.com/news/2023-02-fructose-alzheimer-disease.html

Can hearing loss be reversed?

 Taking a bite of an apple is considered a healthy choice. But have you ever thought about putting in earplugs before your favorite band takes the stage?

Just like your future body will thank you for the apple, your future ears (specifically your cochlear hair cells) will thank you for protecting them. The most common cause of hearing loss is progressive because these hair cells—the primary cells to detect sound waves—cannot regenerate if damaged or lost. People who have repeated exposure to loud noises, like military personnel, construction workers, and musicians, are most at risk for this type of hearing loss. But it can happen to anyone over time (even concertgoers).

On the other hand, birds and fish can regenerate these hair cells, and now researchers at the Del Monte Institute for Neuroscience are getting closer to identifying the mechanisms that may promote this type of regeneration in mammals, as explained in research recently published in Frontiers in Cellular Neuroscience.

"We know from our previous work that expression of an active growth gene, called ERBB2, was able to activate the growth of new hair cells (in mammals), but we didn't fully understand why," said Patricia White, Ph.D., professor of Neuroscience and Otolaryngology at the University of Rochester Medical Center. The 2018 study led by Jingyuan Zhang, Ph.D., a postdoctoral fellow in the White lab at the time, found that activating the growth gene ERBB2 pathway triggered a cascading series of cellular events by which cochlear support cells began to multiply and activate other neighboring stem cells to become new sensory hair cells.

"This new study tells us how that activation is happening—a significant advance toward the ultimate goal of generating new cochlear hair cells in mammals," said White.

Using single-cell RNA sequencing in mice, researchers compared cells with an overactive growth gene (ERBB2 signaling) with similar cells that lacked such signaling. They found the growth gene—ERBB2—promoted stem cell-like development by initiating the expression of multiple proteins—including SPP1, a protein that signals through the CD44 receptor. The CD44 receptor is known to be present in cochlear-supporting cells. This increase in cellular response promoted mitosis in the supporting cells, a key event for regeneration.

"When we checked this process in adult mice, we were able to show that ERBB2 expression drove the protein expression of SPP1 that is necessary to activate CD44 and grow new hair cells," said Dorota Piekna-Przybylska, Ph.D., a staff scientist in the White Lab and first author of the study. "This discovery has made it clear that regeneration is not only restricted to the early stages of development. We believe we can use these findings to drive regeneration in adults."

"We plan to further investigation of this phenomenon from a mechanistic perspective to determine whether it can improve auditory function after damage in mammals. That is the ultimate goal," said White.

Additional authors include Daxiang Na, Cameron Baker, and John Ashton, Ph.D., at the University of Rochester and Medical Center.

More information: Dorota Piekna-Przybylska et al, Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation, Frontiers in Cellular Neuroscience (2023). DOI: 10.3389/fncel.2022.1096872

https://medicalxpress.com/news/2023-02-loss-reversed-reveals-clues-regrow.html

Changes in how heart produces energy may be earliest sign of cardiac deterioration

 Heart failure is often identified only when the heart has already deteriorated. This is in large part because the cause is unknown for about 70% of people who experience heart failure.

Researchers at The Hospital for Sick Children (SickKids) have discovered that one of the earliest signs of heart failure is a change in how the heart produces energy, with findings offering a potential way to preempt heart failure before the heart begins to deteriorate.

Led by Dr. Paul Delgado-Olguín, a scientist in the Translational Medicine program, the research may also help to explain the diversity of causes underlying heart failure.

"We were surprised to find that dysregulation of energy production was the earliest sign of heart failure," says Delgado-Olguín. "People associate deficiency in energy production with later stage heart failure, but our findings show this could actually be the cause of heart failure, not a result."

In a healthy heart, a protein called lysine demethylase 8 (Kdm8) helps to maintain a balanced energy use, also known as metabolism, by repressing TBX15, another protein that decreases energy production.

In a study published today in Nature Cardiovascular Research, the research team analyzed a large dataset on gene expression, the process by which DNA is converted to proteins, in human hearts at a later stage of heart failure and found that KDM8 was less active. This allowed TBX15 to be more highly expressed, leading to changes in metabolism. Researchers also found that TBX15 was expressed at the highest levels in hearts where energy production genes were most strongly suppressed.

"There are many genes that help regulate energy production in our bodies, but we were able to identify changes in specific proteins that occur well before cardiac deterioration," says Delgado-Olguín.

After identifying change in energy production as an early sign of heart failure, the research team drilled down further to explore how metabolic pathways could be modified to prevent the failure. In doing so they found that the nicotinamide adenine dinucleotide (NAD+) pathway, which regulates energy metabolism, was less active. The team was then able to intervene and prevent heart failure in a mouse model by providing NAD+ injections and boosting energy production.

"This research suggests it may be possible to alter certain metabolic pathways to prevent heart failure before damage to the heart begins," says Delgado-Olguín. "Our research sets the stage to identify children and adults that may be at a higher risk of heart failure, and to improve energy balance in their hearts to prevent it."

For the study team, this research is helping contribute to the future of Precision Child Health at SickKids, a movement to deliver individualized care for every child.

"Heart failure is so diverse," says Delgado-Olguín. "But if we could determine that an individual's particular heart is not using energy efficiently early on and is at risk of heart failure, we may be able to predict how they respond to treatment targeted to specific metabolic pathways that could prevent cardiac deterioration."

While international research on NAD+ treatment in late-stage heart failure is underway, the team hopes that this latest research from the Delgado-Olguín Lab will spark new research on early identification and preventative treatment.

More information: Abdalla Ahmed et al, KDM8 epigenetically controls cardiac metabolism to prevent initiation of dilated cardiomyopathy, Nature Cardiovascular Research (2023). DOI: 10.1038/s44161-023-00214-0

https://medicalxpress.com/news/2023-02-heart-energy-earliest-cardiac-deterioration.html

Quebec tells Eric Adams to stop buying NY migrants bus tickets

 The government of Canada’s largest province is demanding that Mayor Eric Adams “immediately” stop helping migrants illegally enter the Great White North, as recently revealed by The Post.

“Any form of assistance to migrants crossing the border where it is strictly forbidden to do so should stop immediately,” a spokesperson for Quebec Premier Francois Legault said.

“We understand that the situation of migrants in New York poses major challenges, but the situation in Quebec and particularly in Montreal is even worse and constitutes an important humanitarian issue.”

Earlier this month, The Post exclusively reported that Adams was using taxpayer funds to get bus tickets for migrants in the Big Apple to travel upstate to Plattsburgh.

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Migrants from NYC cross the US-Canadian border in Champlain, NY.

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Guards warn migrants that if they cross the border into Canada, they will be arrested.

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Migrants must walk 100 feet to cross the border.

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From there, migrants take taxis and vans to a cul-de-sac at the end of Roxham Road in Champlain, where they walk across the border and surrender to Canadian Mounties to seek asylum, as The Post documented on Feb. 5.

As many as 250 migrants use the Roxham Road crossing to illegally enter Canada each day, with nearly all of them settling in Montreal, Quebec’s biggest city, Legault spokesperson Ewan Sauves said.

The situation has overwhelmed Montreal’s ability to provide housing and other public services, with the flood of new students alone equivalent to the opening of 13 new schools, he said.

Last year, 39,161 people used Roxham Road to illegally enter Canada, comprising 99.1% of all such border crossings, Sauves said.

By comparison, the latest figures released by City Hall on Monday showed that officials have processed more than 45,600 migrants since the spring, with about 29,100 housed in 91 emergency shelters as of Sunday.

Mayor Eric Adams has defended funding nonprofits to “reticket” migrants who want to leave the city and go to Canada.

Paul Martinka

Those figures likely represent an undercount, however, because they don’t include migrants who stay with relatives, friends and other people in their networks after arriving in New York, according to City Hall.

But while the Big Apple’s population is nearly 8.5 million, Montreal’s is just 1.7 million.

Adams’ office didn’t immediately return a request for comment, but the mayor last week defended funding various nonprofits, including Catholic Charities, to “reticket” migrants who want to leave the city and go to Canada.

Quebec Premier Francois Legault said all aiding of migrants crossing the border “should stop immediately.”

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“We are not encouraging anyone to go to another country,” Adams said during a Wednesday appearance on CNN. “If we speak with a migrant, interview them, [we] find out their desires and make sure that we are assisting them like we’ve done.”

The surge in border crossings at Roxham Road has sparked controversy in Quebec, with the separatist Parti Québécois recently calling for police intervention and the creation of an “enclave” to block the Roxham Road path between the US and Canada.

Another separatist political party, Bloc Québécois, tweeted Friday that Quebec was not an “all-inclusive,” sparking outrage from the democratic socialist party Québec solidaire, the Canadian Press reported Sunday.

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Mayor Eric Adams used taxpayer funds to get bus tickets for migrants to travel upstate to Plattsburgh.

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From Plattsburgh, migrants take taxis and vans to the border crossing at the end of Roxham Road in Champlain.

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“An all-inclusive is a place where we go to crash on the beach drinking margaritas,” Québec solidaire spokesperson Gabriel Nadeau-Dubois said while attending the party’s national council in Montreal.

“The people who enter Quebec to apply for asylum are people who are fleeing violence, exploitation, persecution. They are not people who want to take it easy.”

Nadeau-Dubois added: “These comparisons have no place.”

https://nypost.com/2023/02/13/quebec-tells-eric-adams-to-stop-buying-ny-migrants-bus-tickets/