Insulin-like hormones seen critical for brain plasticity

 Research from the Max Planck Florida Institute for Neuroscience has identified a mechanism through which insulin-like growth factors facilitate brain plasticity.

The insulin superfamily of hormones, including insulin, insulin-like growth factor 1 (IGF1), and insulin-like growth factor 2 (IGF2), play a crucial role not only in regulating blood sugar, metabolism, and growth, but also in healthy brain development and function, including learning and memory.

These hormones can enter the brain through the bloodstream from the liver or can be synthesized directly in neurons and glial cells within the brain. They bind to receptors, including the IGF1-receptor, activating signals that modulate neuron growth and activity. Disruption of this signaling pathway is involved in cognitive decline and diseases such as Alzheimer's.

To understand how IGF1 and IGF2 promote brain health, scientists investigated the activation of this signaling pathway in the hippocampus, an area of the brain critical for learning and memory. Specifically, they wanted to explore whether IGF signaling was active during synaptic plasticity, the cellular process that strengthens connections between neurons during memory formation and protects against cognitive decline. The research is published in the journal Science Advances.

To do this, Max Planck scientists developed a biosensor that detected when the IGF1-Receptor was active, allowing them to visualize the activity of the signaling pathway involved in plasticity. When a synapse was undergoing plasticity, the scientists observed that the IGF1-Receptor was robustly activated in the strengthening synapse and nearby synapses. This receptor activation was critical for synaptic growth and strengthening during plasticity. However, where the IGF that activates the receptor was coming from was unknown.

Lead researcher and first author of the scientific publication, Dr. Xun Tu, however, described how being able to visualize the receptor activation during plasticity gave them a clue. "The fact that the activation of the IGF-receptor was localized near the synapse undergoing plasticity suggested that IGF1 or IGF2 might be produced in hippocampal neurons and locally released during plasticity," she explained.

To explore this hypothesis, the scientists tested whether IGF1 and IGF2 were produced and could be released from hippocampal neurons.

Interestingly, they found a region-specific difference in the production of IGF1 and IGF2. One group of neurons in the hippocampus, CA1 neurons, produced IGF1; another group, CA3 neurons, produced IGF2. When either CA1 or CA3 neurons were activated in a way that mimicked synaptic plasticity, IGF wasreleased. Importantly, when the scientists disrupted the ability of the neurons to produce IGF, the activation of the IGF1-Receptor during plasticity and synaptic growth and strengthening was blocked.

Senior author on the publication and Max Planck Scientific Director, Dr. Ryohei Yasuda, summarized the findings. "This work reveals a local, autocrine mechanism in neurons that is critical for brain plasticity. When a synapse undergoes plasticity, IGF is released locally to activate the IGF1-Receptor on the same neuron. Disrupting this mechanism impairs the plasticity, highlighting its critical role in maintaining cognitive health."

This discovery of this new mechanism sheds light on how memories are encoded in the brain and highlights the importance of further study on the insulin superfamily of hormones in the brain. The scientists hope that understanding the mechanism through which IGF hormones facilitate brain plasticity, will lead to research into whether targeting this signaling pathway could prevent cognitive decline and combat diseases like Alzheimer's.

More information: Xun Tu et al, Local autocrine plasticity signaling in single dendritic spines by insulin-like growth factors, Science Advances (2023). DOI: 10.1126/sciadv.adg0666

https://medicalxpress.com/news/2023-08-insulin-like-hormones-critical-brain-plasticity.html

Cannabis use during pregnancy could cause lifelong cognitive deficits for offspring

 While previous research has shown that prenatal cannabis exposure can obstruct the normal growth of a fetus, the long-term impacts on brain development are still unknown. Western researchers are now providing fresh insight into this area, while also identifying a possible direction to treat the adverse effects.

Led by Addictions Research Group member Mohammed H. Sarikahya and Schulich Medicine & Dentistry professor Steven Laviolette, a new study, published in the journal Molecular Psychiatry has shown that prenatal exposure to cannabis in rodents led to lasting, substantial effects on cognitive and memory functions.

Interestingly, these effects are sex-specific, suggesting males and females may be affected differently by cannabis exposure in the womb.

According to the Canadian Center on Substance Use and Addiction, cannabis usage is reported among up to 22% of Canadian pregnant women aged 18–24, underlining the critical significance of the study's findings.

"Over the past two decades, concentrations of THC—the primary psychoactive component in cannabis—have risen from 3% to 22%. THC can pass through the placenta and impact the developing fetal brain," said Sarikahya.

"Our research shows that prenatal THC exposure can lead to serious cognitive and memory deficits that are sex-dependent, enduring and potentially lifelong," said Sarikahya.

The team of researchers used a variety of tests to measure the effects of prenatal THC exposure on animal models, including social interaction, spontaneous alternation and object recognition tests. These assessments showed that prenatal exposure to THC significantly impacted the offspring's desire to socialize, memory of previous social encounters and learning capabilities in both males and females.

Most importantly, the study also suggests a potential solution to these effects. By targeting irregularities in brain fatty acids it might be possible to reduce the adverse impacts of prenatal cannabis exposure.

The researchers found that THC disrupts the fetal endocannabinoid system (ECS), a key player in fetal and adolescent neurodevelopment, as well as cognitive and emotional processing.

"This disruption leads to deficiencies in vital fatty acids like DHA and ARA, potentially causing lifelong health disturbances," said Laviolette, professor in the department of anatomy and cell biology at Schulich Medicine & Dentistry.

Delving into the molecular impacts, the researchers found changes in levels of important fatty acids in the brain and variations in certain protein levels, both critical for normal brain function. These alterations were more pronounced in adult males and differed depending on the specific region of the brain.

The study also underscores the distinct impacts of prenatal cannabis exposure between males and females. Both male and female offspring showed cognitive deficits, but the mechanisms differed significantly between the sexes.

The study found that females showed very active brain activity in a part of the brain called the ventral hippocampus. The ventral hippocampus is a part of the brain involved in things like emotion and memory. On the other hand, males showed less active brain activity in this same area.

"This suggests prenatal cannabis exposure can have sex-specific effects on the developing brain, leading to different patterns of cognitive and behavioral disturbances in males and females," said Laviolette.

More information: Mohammed H. Sarikahya et al, Prenatal THC exposure induces long-term, sex-dependent cognitive dysfunction associated with lipidomic and neuronal pathology in the prefrontal cortex-hippocampal network, Molecular Psychiatry (2023). DOI: 10.1038/s41380-023-02190-0

https://medicalxpress.com/news/2023-08-cannabis-pregnancy-lifelong-cognitive-deficits.html

New Evidence Suggests Vaccinated Can Transmit Covid-19 Vax Antibodies Through The Air

 by Megan Radshaw JD via The Epoch Times (emphasis ours),

New evidence suggests vaccinated individuals can transmit antibodies generated through mRNA COVID-19 vaccination to unvaccinated individuals through aerosols, according to a peer-reviewed study (pdf) published in ImmunoHorizons.

Extended mask requirements allowed scientists at the University of Colorado to evaluate whether vaccinated individuals could transfer aerosolized antibodies generated from COVID-19 vaccines. Aerosols are a manufactured or naturally occurring suspension of particles or droplets in the air, such as airborne dust, mists, fumes, or smoke, that can be absorbed by the skin or inhaled.

Researchers used a combination of tests to detect SARS-CoV-2-specific antibodies from masks vaccinated lab members wore and donated anonymously at the end of the day. Antibodies are proteins produced by the immune system that circulate in the blood and neutralize foreign substances such as bacteria and viruses.

Consistent with results reported by others, the researchers identified both immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies in the saliva of vaccinated individuals and on their masks.

Based on their observations, the researchers hypothesized droplet or aerosolized antibody transfer might occur between individuals, similar to how droplets and aerosolized viral particles are transferred by the same route.

To test their hypothesis, they obtained and compared nasal swabs from unvaccinated children living in vaccinated, unvaccinated, and COVID-19-positive households.

Results showed high IgG in the noses of vaccinated parents was “significantly associated” with an increase in intranasal IgG within the unvaccinated child from the same household, especially compared to the “complete deficit of SARS-CoV-2-specific antibody detected” in nasal swabs obtained from children in nonvaccinated families. A similar trend was found with IgA in the same samples.

In other words, their findings suggest aerosol transmission of antibodies can occur between COVID-19 vaccinated parents and their children—and the tendency for this transfer is directly related to the amount of nasal or oral antibodies found in those who received vaccines.

This type of shedding is called “passive immunization,” where antibodies—primarily IgA—are actually exchanged between individuals through respiratory droplets, Brian Hooker, chief scientific officer at Children’s Health Defense, who holds a doctorate in biochemical engineering, wrote in an email to The Epoch Times. “But this would provide minimal immunity for the ‘bystanders’ based on the fact that the original mRNA vaccines provide so little protection.”

Mr. Hooker said passive immunization could elicit autoimmunity and “all sorts of reactions” in bystanders due to a similar “molecular mimicry between the COVID-19 Ig [immunoglobulin] antibodies and human proteins.”

Studies have shown that molecular mimicry between the foreign molecules and human molecules can lead to an autoimmune response causing antibodies to function incorrectly and interact against human proteins. Autoimmunity refers to an immune reaction where the body attacks its own tissues, resulting in damage or disease.

Mr. Hooker said the study suggests that if Ig antibodies can be transmitted person-to-person, there is a possibility the spike protein generated by COVID-19 vaccines could be transmitted as well.

“This could cause immunization of the bystanders as well as problems associated with spike protein toxicity to bloodstream components and other tissues,” he added.

COVID-19 Vaccines Were Authorized Without Studies to Assess Transmission

COVID-19 vaccines using mRNA technology like Pfizer and Moderna were authorized globally without studies into the possible expression of lipid nanoparticles (LNPs) containing the mRNA or of the spike protein manufactured by the cells of a recently vaccinated individual.

https://www.zerohedge.com/covid-19/new-evidence-suggests-mrna-covid-19-vaccine-transmission-aerosols-vaccinated-unvaccinated

Common blood thinner may double as cancer therapy

 Warfarin, a widely used blood thinner, appears to have potent anti-cancer properties, according to a study by Columbia University researchers. The study, conducted in human cells and in mice, found that warfarin stops tumors from interfering with a self-destruct mechanism that cells initiate when they detect mutations or other abnormalities.

"Our findings suggest that warfarin, which is already approved by the FDA, could be repurposed to treat a variety of cancers, including pancreatic cancer," says study leader Wei Gu, Ph.D., the Abraham and Mildred Goldstein Professor of Pathology & Cell Biology (in the Institute for Cancer Genetics) at Columbia University Vagelos College of Physicians and Surgeons.

The study is titled "Regulation of VKORC1L1 is critical for p53-mediated tumor suppression through vitamin K metabolism," and it was published July 18 in Cell Metabolism. Postdoctoral researcher scientists Xin Yang, Ph.D., and Zhe Wang, Ph.D., contributed equally as first authors.

Death by ferroptosis

The warfarin discovery was an unexpected finding from a study designed to uncover molecular processes that regulate ferroptosis, a cell death mechanism recently discovered by Columbia chemist Brent Stockwell, Ph.D., associate professor in the Departments of Biological Sciences and Chemistry, and other scientists.

Cancer researchers are excited by the idea of harnessing ferroptosis—so-named because it requires iron to work—to kill cancer cells. Drugs that induce ferroptosis may be particularly useful for cancers that elude current treatments.

To learn more about how ferroptosis is controlled in the cell, Gu, Stockwell, and their colleagues performed genetic screens on human melanoma cells to identify genes that contribute to ferroptosis. As expected, the screens identified several previously known ferroptosis genes, but a new one stood out: VKORC1L1.

In laboratory experiments, the researchers found that VKORC1L1 is a potent inhibitor of ferroptosis, and loss of VKORC1L1 sensitizes cells to ferroptotic cell death.

VKORC1L1 levels also have clinical consequences, an analysis of human cancer data then revealed: Patients with low levels of VKORC1L1 activity generally lived longer than patients with higher levels.

Warfarin promotes ferroptosis in cancer cells

Warfarin (also known by the trade name coumadin) was first approved for medical use in 1954. It has since become a mainstay therapy for preventing blood clots, which can cause stroke, heart attack, or pulmonary embolism.

Warfarin is also a known VKORC1L1 inhibitor, so the researchers explored its potential as a cancer drug. They found that warfarin, by reducing VKORC1L1 activity, sensitized human pancreatic cancer cells to ferroptosis and strongly repressed tumor growth in a mouse model of pancreatic cancer.

Data from other studies also support the idea that warfarin has potential against cancer. Warfarin and other anticoagulants are commonly given to cancer patients, who are at increased risk for blood clots. Recently, investigators have noticed that pancreatic, gastric, and colorectal cancer patients who received warfarin survived significantly longer than those taking other anticoagulants.

"Since warfarin has been extensively used in the clinic in cancer patients, we think warfarin could be tested soon as an anticancer drug, particularly for tumors with high levels of VKORC1L1 expression," Gu says.

That may extend beyond pancreatic and gastric cancers to many other types, Gu adds. The researchers also found that VKORC1L1 is a direct target of p53, a well-known tumor suppressor gene that is mutated in more half of all cancers.

More information: Xin Yang et al, Regulation of VKORC1L1 is critical for p53-mediated tumor suppression through vitamin K metabolism, Cell Metabolism (2023). DOI: 10.1016/j.cmet.2023.06.014

https://medicalxpress.com/news/2023-08-common-blood-thinner-cancer-therapy.html

What happens in brain under influence of psychedelics, meditating, hypnosis

 Changes in a person's "normal" mental state after taking drugs, while meditating, during hypnosis or due to specific medical conditions have been a topic of study for several years now. Some of these mental changes, which are known as altered states of consciousness, have been found to have potentially beneficial effects, reducing stress and fostering greater well-being.

Researchers at University of Zurich's Psychiatric Hospital have recently been exploring the potential of psychedelic drugs, such as psilocybin and lysergic acid diethylamide (LSD) for treating depression and other mental disorders. In a recent paper published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, they compared the brains of people who had taken psychedelics to those of others who were meditating or were hypnotized.

"Our group has plenty of experience studying altered states," Nathalie Rieser, one of the researchers who carried out the study, told Medical Xpress. "We have been investigating the effects of psychedelics on the brain in various studies, given that altered states of consciousness are becoming increasingly relevant in the treatment of psychiatric disorders. Anecdotally, people often report similarities in experiences induced by hypnosis, meditation, or psychedelics. However, our neurobiological understanding of these states is only just evolving."

While many studies looked at individual altered states of consciousness and how they manifest in the brain, comparisons between these states remain scarce. Rieser and her colleagues wished to fill this gap in the literature, by comparing the neural correlates of psychedelics, meditation and hypnosis.

"We did not know if the same neurobiological alterations give rise to the experience of all altered states or whether these states are different on a brain-level," Rieser said.

Rather than conducting a single experiment that collectively involved psychedelics, meditation and hypnosis, the researchers analyzed datasets conducted during four distinct experimental trials. The first two trials examined the effects of two different psychedelic drugs on the brain, namely psilocybin and LSD, while the last two focused on hypnosis and meditation.

"We combined four different datasets that were collected at the Psychiatric University Hospital in Zurich using the same MRI-scanner," Rieser explained. "For the psychedelic studies, we included healthy participants who subsequently received psilocybin, LSD, or a placebo, whereas the meditation and hypnosis studies were conducted with participants who were experts in the respective field to make sure they can reach the state in an MR environment."

During the team's four experimental trials, all participants were asked to simply lay inside an MRI scanner without completing any task or engaging in any activity. The MRI scanner recorded their brain activity both while they were in a normal state of consciousness and under the altered state of consciousness relevant to that trial (i.e., after taking psychedelics, while meditating or while under hypnosis).

"We analyzed the participants' brain activity throughout the whole brain and investigated whether different brain areas work together in a distinct way compared to the baseline scan," Rieser said. "Our findings showed that even though psilocybin, LSD, meditation and hypnosis induce overlapping subjective effects, the underlying brain changes are distinct."

The findings gathered by this team of researchers suggest that while some might report having similar experiences or feelings under these different states of consciousness, what is happening in their brain is actually very different. While psilocybin and LSD appeared to produce similar brain activity, the changes they induced were markedly different from those observed during meditation or hypnosis. This suggests that psychedelics, meditation and hypnosis have distinct underlying mechanisms of action and overall different effects on the brain.

Overall, these results suggest that these three distinct states may have synergistic therapeutic effects and may not therapeutically substitute each other. In the future, they could pave the way for further investigations of their unique strengths and benefits, potentially informing the development of new promising therapeutic strategies for psychiatric disorders.

"We are now simultaneously working on investigating mechanisms of action of psychedelics in healthy controls as well as their clinical application in the treatment of patients with alcohol use disorder and major depressive disorder," Rieser added. "We are assessing their efficacy and exploring brain, behavioral, and cognitive changes in response to psychedelic-assisted therapy. The current study is informing future investigations on optimizing psychedelic-assisted therapy."

More information: Flora F. Moujaes et al, Comparing neural correlates of consciousness: from psychedelics to hypnosis and meditation, Biological Psychiatry: Cognitive Neuroscience and Neuroimaging (2023). DOI: 10.1016/j.bpsc.2023.07.003

https://medicalxpress.com/news/2023-08-exploring-brain-psychedelics-meditating-hypnosis.html

RFK Jr. Sues Google, YouTube Over Censorship

 Democratic presidential candidate Robert F. Kennedy Jr. has filed a lawsuit against Google and YouTube, who he claims are 'state actors' who have violated his free speech.

Kennedy, who's campaigning against President Joe Biden for the Democratic party nomination said in a 27-page complaint that the sites caved to pressure from the Biden administration, and that his videos about Covid vaccines were being censored through "overt and covert" means.

"Under these circumstances, YouTube is a state actor and it violated Mr Kennedy’s First Amendment rights by engaging in viewpoint discrimination," reads the filing. "This complaint concerns the freedom of speech and the extraordinary steps the United States government has taken under the leadership of Joe Biden to silence people it does not want Americans to hear."

The lawsuit points to several instances of the sites removing Kennedy's speeches and interviews, including one with Joe Rogan, and a March speech he gave to the New Hampshire Institute of Politics.

"Unlike other tech companies — notably Facebook and Instagram (both owned by Facebook parent Meta) and Twitter (now owned by Elon Musk) — YouTube has not treated Mr Kennedy differently now that he is a political candidate," the suit states.

"Although it cited its own COVID vaccine misinformation policies when censoring Mr. Kennedy, the policies rely entirely on government officials to decide what information gets censored," reads the complaint. "They say that YouTube does not allow people to say anything ‘that contradicts local health authorities’ (LHA) or the World Health Organization’s (WHO) medical information about COVID-19.'"

According to the complaint, while other social media companies have stopped suppressing Kennedy since he declared his candidacy, YouTube has continued to silence him. "This censorship campaign prevents Mr. Kennedy’s message from reaching millions of voters. It also makes it harder for groups that are supporting his campaign to amplify his message through public sources."

Last month, the 69-year-old told the GOP's House Subcommittee on the Weaponization of the Federal Government that he's being censored by a cabal of "big government, big tech and big media."

In response, Google told The Independent: "YouTube applies its Community Guidelines independently, transparently, and consistently, regardless of political viewpoint.

"These claims are meritless and we look forward to refuting them."

Kennedy also filed a class action lawsuit against Biden and the US Government in March for attempting to induce Facebook, Google and Twitter to "censor constitutionally protected speech."

https://www.zerohedge.com/political/rfk-sues-google-youtube-over-censorship

Medical Students Are Skipping Class Lectures: Does It Matter?

 Medical students are taking more control over how and when they learn. It's a practice propelled by the pandemic, but it started long before COVID shifted many traditional classrooms to virtual education.

New technologies, including online lectures and guided-lesson websites, along with alternative teaching methods, such as the flipped classroom model, in which med students complete before-class assignments and participate in group projects, are helping to train future physicians for their medical careers.

So though students may not be attending in-person lectures like they did in the past, proponents of online learning say the education students receive and the subsequent care they deliver remains the same.

Association of American Medical Colleges' (AAMC's) most recent annual survey of second-year medical students found that 25% "almost never" attended their in-person lectures in 2022. The figure has steadily improved since 2020 but mirrors what AAMC recorded in 2017.

"The pandemic may have exacerbated the trend, but it's a long-standing issue," said Katherine McOwen, senior director of educational and student affairs at AAMC. She told Medscape Medical News that she's witnessed the pattern for 24 years in her work with medical schools.

"I know it sounds alarming that students aren't attending lectures. But that doesn't mean they're not learning," said Ahmed Ahmed, MD, MPP, MSc, a recent graduate of Harvard Medical School and now a resident at Brigham and Women's Hospital.

Today's generation of medical students grew up in the age of technology. They are comfortable in front of the screen, so it makes sense for them to learn certain aspects of medical sciences and public health in the same way, Ahmed told Medscape Medical News.

Ahmed said that at Harvard, he participated in one or two case-based classes per week that followed a flipped classroom model, which allows students to study topics on their own before discussing in a lecture format as a group. "We had to come up with a diagnostic plan and walk through the case slide by slide," he said. "It got us to think like a clinician."

The flipped classroom allows students to study at their own pace using their preferred learning style, leading to more collaboration in the classroom and between students, according to a 2022 article on the "new standard in medical education" published in Trends in Anaesthesia & Critical Care.

Students use online education tools to complete pre-class assignments such as watching short videos, listening to podcasts, or reading journal articles. In-class time can then be used to cement and create connections through discussions, interactive exercises, group learning, and case studies, the article stated.

Benefits of the flipped classroom include student satisfaction, learner motivation, and faculty interest in learning new teaching methods, according to the article: "Students are performing at least as well as those who attended traditional lectures, while some studies in select healthcare settings show increased retention in flipped classroom settings."

Another study on the flipped classroom, published in BMC Medical Education in 2018, found that the teaching method was superior to traditional classrooms for health professions education. Researchers focused specifically on flipped classrooms that provided prerecorded videos to students.

Molly Cooke, MD, director of education for global health sciences at the University of California San Francisco School of Medicine, said that the school no longer requires attendance at lectures. "Personally, my position is that medical students are very busy people and make, by and large, rational decisions about how to spend their time. As learning and retention from 50-minute lectures has been shown for decades to be poor, I think it's perfectly reasonable to watch lectures on their own time."

Ahmed agrees. "By our standards, the old model is archaic. It's passive, and instead we should be encouraging lifelong, self-directed learning."

To that end, Ahmed and his fellow students also relied heavily during medical school on secondary educational sources such as Boards and Beyond and Sketchy. "There's an entire community of medical school students across the country using them," Ahmed explained. "You can learn what you need in a tenth of the time of lectures."

Today lectures only provide a portion of the information delivered to students, McGowen said. "They also learn in small groups, in problem-solving sessions, and in clinical experiences, all of which make up the meat of their education."

The purpose of medical school is to prepare students for residency, she added. "Medical school education is very different from other types of education. Students are examined in a variety of ways before they move on to residency and ultimately, practice."

For example, every student must pass the three-part United States Medical Licensing Examination. Students complete the first two parts in medical school and the third part during residency. "The tests represent a combination of everything students have learned, from lectures, clinical time, and in self-directed learning," McGowen said.

Post-pandemic, the tools and styles of learning in medical education have changed, and they are likely to continue to evolve along with students and technology, according to the 2022 article on the flipped classroom. "The future of medical education will continue to move in ways that embrace digital technology, as this is what digital native learners are increasingly expecting for their healthcare education," states the article.

https://www.medscape.com/viewarticle/994751