New research conducted on mice suggests repeated heavy drinking causes synaptic dysfunctions that lead to anxiety.
- The study was conducted on mice, who were given the equivalent of five drinks daily for 10 days.
- Images of the alcoholic mice brains showed synaptic dysfunctions related to microglia (immune cells in the brain).
- The results suggest that regulating TNF, a signaling protein related to systemic inflammation, may someday play a part in treating alcohol addiction.
3D surface rendering of confocal maximum projection images showing volume reconstruction of PSD-95 within CD68 structures in microglia (Iba1+ cell) on tissue sections from prefrontal cortices of WT and TNF KO mice after exposure to EtOH or H2O
The role of TNF in anxiety<p>But the new study revealed an interesting finding about TNF. To find out how TNF interacts with anxiety, the researchers gave to the alcoholic mice a drug called <a href="https://www.drugs.com/mtm/pomalidomide.html" target="_blank">pomalidomide</a>, which blocks the production of TNF. After, the mice showed improved synaptic functioning and less anxiety-like behaviors.</p><p style="margin-left: 20px;">"This study suggests that regulating the levels of TNF might eventually be useful when treating alcohol addiction," Relvas told Inverse.</p>
Pixabay<p>Still, it's unclear whether or how TNF regulation might work its way into alcohol addiction treatments. After all, even if science can fix the anxiety aspect of alcoholism, heavy drinking still exacts heavy tolls on other parts of the body and brain.</p><p>For now, it's probably best to keep your drinking within moderate levels: <a href="https://health.gov/our-work/food-nutrition/2015-2020-dietary-guidelines/guidelines/appendix-9/" target="_blank">Most</a> <a href="https://www.nytimes.com/2018/08/27/health/alcohol-drinking-health.html" target="_blank">research</a> suggests that having one to two drinks per day yields no significant negative health consequences.</p>
This could change how researchers approach vaccine development.
- The reason children suffer less from the novel coronavirus has remained mysterious.
- Researchers identified a cytokine, IL-17A, which appears to protect children from the ravages of COVID-19.
- This cytokine response could change how researchers approach vaccine development.
A member of staff wearing personal protective equipment (PPE) takes a child's temperature at the Harris Academy's Shortland's school on June 04, 2020 in London, England.
Photo by Dan Kitwood/Getty Images<p>Experts don't want to place kids at the back of the line, regardless of how strong their immune systems appear. At least one company, Moderna, <a href="https://www.businessinsider.com/coronavirus-vaccine-for-kids-moderna-plans-pediatric-trial-2020-9" target="_blank">hopes to begin testing</a> vaccines in pediatric volunteers by year's end.</p><p>Innate immune response is especially high during childhood (compared to adaptive immunity). This makes evolutionary sense: nature wants an animal to survive until its ready to procreate. Turns out the children in the study possessed high levels of cytokines that boost their immune response. The biggest impact is made by IL-17A, which appears to protect the youngest cohort from the ravages of the coronavirus. </p><p>While both age groups produced antibodies to fight off the infamous spike protein, adults that produce neutralizing antibodies actually suffer a <em>worse</em> fate. Herold says this "over-vigorous adaptive immune response" might promote inflammation, triggering acute respiratory distress syndrome (ARDS). </p><p>This matters for vaccine development. As Herold says, </p><p style="margin-left: 20px;">"Our adult COVID-19 patients who fared poorly had high levels of neutralizing antibodies, suggesting that convalescent plasma—which is rich in neutralizing antibodies—may not help adults who have already developed signs of ARDS. By contrast, therapies that boost innate immune responses early in the course of the disease may be especially beneficial."</p><p>Herold says current vaccine trials are focused on boosting neutralizing-antibody levels. With this new information, researchers may want to work on vaccines that boost the innate immune response instead. </p><p>With <a href="https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html" target="_blank">at least 55 vaccine trials</a> underway, every piece of data matters. </p><p>--</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a>, <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank">Facebook</a> and <a href="https://derekberes.substack.com/" target="_blank" rel="noopener noreferrer">Substack</a>. His next book is</em> "<em>Hero's Dose: The Case For Psychedelics in Ritual and Therapy."</em></p>
Researchers from the University of Toronto published a new map of cancer cells' genetic defenses against treatment.
A moving target<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQzNjQ2Ny9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY1MDM3OTA0N30.z4u2eaulqRu8cslqqny8t9G7iaHr_DarbDJSFKLdDwI/img.jpg?width=980" id="21b22" class="rm-shortcode" data-rm-shortcode-id="aefbbccdf3bb0d25bf14268ab87a821f" data-rm-shortcode-name="rebelmouse-image" alt="IV drip" />
Credit: Marcelo Leal/Unsplash<p>Speaking to <a href="https://www.utoronto.ca/news/u-t-researchers-identify-genes-enable-cancer-evade-immune-system" target="_blank" rel="noopener noreferrer">U of T News</a>, lead author of the study molecular geneticist <a href="http://www.moleculargenetics.utoronto.ca/faculty/2014/9/30/jason-moffat" target="_blank" rel="noopener noreferrer">Jason Moffat</a> of the university's <a href="https://ccbr.utoronto.ca/donnelly-centre-cellular-and-biomolecular-research" target="_blank" rel="noopener noreferrer">Donnelly Centre for Cellular and Biomolecular Research</a> says, "Over the last decade, different forms of immunotherapy have emerged as really potent cancer treatments, but the reality is that they only generate durable responses in a fraction of patients and not for all tumor types."</p><p>There can be a significant degree of heterogeneity between cancer cells from human to human, and even within the same person, making the development of therapies maddeningly difficult. Attempting to address potential cancer-cell vulnerabilities across these variations is a life-or-death game of whack-a-mole.</p><p>"It's an ongoing battle between the immune system and cancer, where the immune system is trying to find and kill the cancer whereas the cancer's job is to evade that killing," says Moffat.</p>
Mapping the mechanisms<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQzNjQ3Ni9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyMjQ1OTM0MX0.HNtivrlU9VBYxcG9JaWKvPJ5RrBsgqd8Fw6ohfSpfh0/img.jpg?width=980" id="0faa6" class="rm-shortcode" data-rm-shortcode-id="7687cdc5abe93503764c1c0401b65fd4" data-rm-shortcode-name="rebelmouse-image" />
Illustration: genes (red, green, and blue spots within the nuclei of HeLa cells) artificially superimposed on images of multi-well plates.
Credit: National Cancer Institute/Unsplash<p>Moffat and his colleagues decided to investigate and identify genes within cancer cells that help them defeat treatment. Co-lead author Keith Lawson of Moffat's lab explains that "it's important to not just find genes that can regulate immune evasion in one model of cancer, but what you really want are to find those genes that you can manipulate in cancer cells across many models because those are going to make the best therapeutic targets."</p><p>To accomplish this, the researchers, working with scientists at <a href="https://www.agios.com" target="_blank">Agios Pharmaceuticals</a> in Cambridge, Massachusetts, first exposed cells from breast, colon, kidney and skin cancer tumors to T cells in lab dishes. This established a baseline of their responses to treatment. Next, using CRISPR, the scientists went through the cells, exhaustively turning off one gene at a time to determine its role in immunotherapy resistance by comparing the cells' response to the T cells compared to their original baseline response.</p><p>The team identified 182 "core cancer intrinsic immune evasion genes" that affected the cells' response to T cells. The fact that some of the identified genes were already known to be involved in resistance provided the researchers with some confidence that they were on the right track.</p><p>Still, many of the genes they ID'ed had not been previously implicated. "That was really exciting to see because it means that our dataset was very rich in new biological information," says Lawson.</p>
It's complicated<p>Unfortunately, Moffat's research also makes clear that defeating cancer-cell resistance is not as simple as removing certain genes. It's true that when the team switched off some of the genes they'd identified, the cancer cells became more vulnerable to T cells, but on the other hand, removal of some other genes made the cancer cells more resistant.</p><p>There also appear to be relationships between multiple genes that complicate matters. </p><p>The team explored the manipulation of the genes that allow cancer cells to engage in <a href="https://en.wikipedia.org/wiki/Autophagy" target="_blank">autophagy</a>, the process by which cells clear out no-longer useful materials to facilitate speedy recovery from damage. Surprisingly, when the researchers deleted certain genes responsible for cancer cells' autophagy, they found the cells' resistance to T cells increased. Apparently, removing one autophagy gene strengthened another mutated autophagy gene.</p><p>"We found this complete inversion of gene dependency," said Moffat. "We did not anticipate this at all. What it shows us is that genetic context — what mutations are present — very much dictates whether the introduction of the second mutation will cause no effect, resistance or sensitivity to therapy."</p><p>There remains a long road ahead when it comes to unraveling cancer cells' resistance to immunotherapy. However, this new study presents a new map that can help scientists navigate what comes next.</p>
UNC School of Medicine researchers identified the amino acid responsible for the trip.
- Researchers at UNC's School of Medicine have discovered the protein responsible for LSD's psychedelic effects.
- A single amino acid—part of the protein, Gαq—activates the mind-bending experience.
- The researchers hope this identification helps shape depression treatment.
What is Bicycle Day?<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="d346092205da3c9ed10bad283222c9f1"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/L32mAiLXnLs?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>Back in the world of clinical science, LSD has always showed promise. That trend continues as restrictions are finally easing up. Understanding LSD's effects on our brain's complex system of networks is an important step toward discovering therapeutic actions. As Roth <a href="https://www.inverse.com/mind-body/how-lsd-binds-to-the-brain-study" target="_blank">says</a> of his research,</p><p style="margin-left: 20px;">"Now we know how psychedelic drugs work – finally! Now we can use this information to, hopefully, discover better medications for many psychiatric diseases."</p><p>Using X-ray crystallography, Roth's team discovered a single amino acid—a building block of the protein, Gαq—responsible for binding to serotonin receptors. As LSD is only a partial agonist, they also experimented with a full-agonist designer psychedelic in order to observe complete receptor activation. This amino acid appears to be the master switch for the psychedelic experience. </p><p>While psilocybin has been in the news, the psychedelic renaissance is expanding in all directions. Phase 1 clinical trials on the <a href="https://newatlas.com/science/landmark-clinical-trial-lsd-mdma-mindmed/" target="_blank">combination</a> of LSD, MDMA, and psychotherapy will soon commence. LSD's effects on <a href="https://clinicaltrials.gov/ct2/show/NCT03866252" target="_blank" rel="noopener noreferrer">Major Depressive Disorder</a> and <a href="https://www.sciencealert.com/first-clinical-trial-shows-micro-doses-of-lsd-can-increase-a-person-s-pain-tolerance" target="_blank">pain management</a> are ongoing. With the <a href="https://www.bloomberg.com/news/articles/2020-09-18/-magic-mushroom-company-moves-toward-mainstream-in-nasdaq-ipo" target="_blank" rel="noopener noreferrer">first psychedelics company</a> to IPO on the American stock market, along with hundreds of millions of dollars of investment flowing into similar companies and organizations, the push for legalized psychedelics intensifies. </p>
Credit: ynsga / Shutterstock<p>Researchers are actively attempting to remove the hallucinogenic component of psychedelics for widespread therapeutic usage—<a href="https://www.healtheuropa.eu/could-ibogaine-offer-a-revolutionary-long-term-solution-to-addiction/100635/" target="_blank">trials</a> using ibogaine for addiction treatment, for example. Identifying the chemical effects of psychedelics on our brains is an essential step in that process.</p><p>Of course, believing psychedelics <em>only</em> matters to brain chemistry is problematic as well. The rituals associated with their use are just as relevant. The "<a href="https://en.wikipedia.org/wiki/Set_and_setting" target="_blank">set and setting</a>" model espoused by Timothy Leary reminds us that biology isn't everything; environmental factors play just as important a role in mental health. </p><p>Isolating specific chemicals without understanding the impact of the drug <em>and</em> the environment overlooks the holistic nature of the psychedelic experience. For example, ketamine trials <a href="https://bigthink.com/surprising-science/ketamine-depression" target="_self">were rushed</a> and could potentially backfire; we can't afford to make that mistake again. </p><p>Still, understanding the pathways LSD utilizes is an important step forward. As Roth says, "Our ultimate goal is to see if we can discover medications which are effective, like psilocybin, for depression but do not have the intense psychedelic actions." In a world where more people are growing anxious and depressed by the day, every intervention should be explored.</p><p> --</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a>, <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank" rel="noopener noreferrer">Facebook</a> and <a href="https://derekberes.substack.com/" target="_blank" rel="noopener noreferrer">Substack</a>. His next book is</em> "<em>Hero's Dose: The Case For Psychedelics in Ritual and Therapy."</em></p>
A team at the University of Basel discovered a connection between antidepressants and REM sleep.
- Researchers at the University of Basel measured the efficacy of antidepressants by measuring brain waves during REM sleep.
- Antidepressants take weeks to begin working, and over 50 percent of users don't find success with the first prescription.
- This research could offer a powerful new diagnostic tool for psychiatrists and doctors.