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Long COVID: How lost connections between nerve cells in the brain may explain cognitive symptoms

<p>For a portion of people who get COVID, symptoms continue for <a href="https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/prevalenceofongoingsymptomsfollowingcoronaviruscovid19infectionintheuk/6october2022" target="_blank" rel="noopener">months or even years</a> after the initial infection. This is commonly referred to as “long COVID”.</p> <p>Some people with long COVID complain of “<a href="https://theconversation.com/what-is-and-what-isnt-brain-fog-190537" target="_blank" rel="noopener">brain fog</a>”, which includes a wide variety of cognitive symptoms affecting memory, concentration, sleep and speech. There’s also growing concern about findings that people who have had COVID are at <a href="https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(22)00260-7/fulltext" target="_blank" rel="noopener">increased risk</a> of developing brain disorders, such as dementia.</p> <p>Scientists are working to understand how exactly a COVID infection affects the human brain. But this is difficult to study, because we can’t experiment on living people’s brains. One way around this is to create <a href="https://www.nature.com/articles/s41578-021-00279-y" target="_blank" rel="noopener">organoids</a>, which are miniature organs grown from stem cells.</p> <p>In a <a href="https://www.nature.com/articles/s41380-022-01786-2.pdf" target="_blank" rel="noopener">recent study</a>, we created brain organoids a little bigger than a pinhead and infected them with SARS-CoV-2, the virus that causes COVID-19.</p> <p>In these organoids, we found that an excessive number of synapses (the connections between brain cells) were eliminated – more than you would expect to see in a normal brain.</p> <p>Synapses are important because they allow neurons to communicate with each other. Still, the elimination of a certain amount of inactive synapses is part of normal brain function. The brain essentially gets rid of old connections when they’re no longer needed, and makes way for new connections, allowing for more efficient functioning.</p> <p>One of the crucial functions of the brain’s immune cells, or <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768411/" target="_blank" rel="noopener">microglia</a>, is to prune these inactive synapses.</p> <p>The exaggerated elimination of synapses we saw in the COVID-infected models could explain why some people have cognitive symptoms as part of long COVID.</p> <p><strong>Parallels with neurodegenerative disorders</strong></p> <p>Interestingly, this pruning process is believed to go awry in several disorders affecting the brain. In particular, excessive elimination of synapses has recently been linked to <a href="https://www.nature.com/articles/s41593-018-0334-7" target="_blank" rel="noopener">neurodevelopmental disorders</a> such as <a href="https://www.nature.com/articles/s41593-018-0334-7" target="_blank" rel="noopener">schizophrenia</a>, as well as <a href="https://www.frontiersin.org/articles/10.3389/fncel.2019.00063/full" target="_blank" rel="noopener">neurodegenerative disorders</a> such as Alzheimer’s and Parkinson’s disease.</p> <p>By sequencing the RNA of single cells, we could study how different cell types in the organoid responded to the virus. We found that the pattern of genes turned on and off by the microglia in our COVID-infected organoids mimicked changes seen in neurodegenerative disorders.</p> <p>This may go some way in explaining the link between COVID and the risk of developing certain neurological disorders.</p> <figure class="align-center "><img src="https://images.theconversation.com/files/491380/original/file-20221024-17-9wi5pg.png?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;fit=clip" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px" srcset="https://images.theconversation.com/files/491380/original/file-20221024-17-9wi5pg.png?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=600&amp;h=338&amp;fit=crop&amp;dpr=1 600w, https://images.theconversation.com/files/491380/original/file-20221024-17-9wi5pg.png?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=600&amp;h=338&amp;fit=crop&amp;dpr=2 1200w, https://images.theconversation.com/files/491380/original/file-20221024-17-9wi5pg.png?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=600&amp;h=338&amp;fit=crop&amp;dpr=3 1800w, https://images.theconversation.com/files/491380/original/file-20221024-17-9wi5pg.png?ixlib=rb-1.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;h=425&amp;fit=crop&amp;dpr=1 754w, https://images.theconversation.com/files/491380/original/file-20221024-17-9wi5pg.png?ixlib=rb-1.1.0&amp;q=30&amp;auto=format&amp;w=754&amp;h=425&amp;fit=crop&amp;dpr=2 1508w, https://images.theconversation.com/files/491380/original/file-20221024-17-9wi5pg.png?ixlib=rb-1.1.0&amp;q=15&amp;auto=format&amp;w=754&amp;h=425&amp;fit=crop&amp;dpr=3 2262w" alt="" /><figcaption><span class="caption">A brain organoid used in our study. You can see the microglial cells in red.</span> <span class="attribution"><span class="source">Sellgren lab</span>, <span class="license">Author provided</span></span></figcaption></figure> <p><strong>A possible target for treatment</strong></p> <p>One limitation of our research is that our organoid models closely resemble the foetal or early brain, rather than the adult brain. So we can’t say for sure whether the changes we noted in our study will necessarily be reflected in the adult brain.</p> <p>However, some <a href="https://pubmed.ncbi.nlm.nih.gov/33248159/" target="_blank" rel="noopener">post-mortem</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/35255491/" target="_blank" rel="noopener">imaging studies</a> report neuronal death and reduction in grey matter thickness in COVID patients, which hints at similar instances of synapse loss caused by an infection in adults.</p> <p>If this proves to be a fruitful line of enquiry, we believe our findings could point to a mechanism contributing to persisting cognitive symptoms after COVID and other viral infections that affect the brain.</p> <p>SARS-CoV-2 is an RNA virus and similar <a href="https://pubmed.ncbi.nlm.nih.gov/27337340/" target="_blank" rel="noopener">processes</a> have been seen in mice infected with other RNA viruses that can also cause residual cognitive symptoms, such as the <a href="https://pubmed.ncbi.nlm.nih.gov/31235930/" target="_blank" rel="noopener">West Nile virus</a>.</p> <p>From here we want to study how different drugs could inhibit the changes we saw in the infected models, hopefully paving the way towards effective treatments. In <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410571/">other research</a>, we’ve observed that an antibiotic called minocycline can reduce the degree to which microglia prune synapses in a dish. So we want to see if this drug can help in our brain organoid models following SARS-CoV-2 infection.<!-- Below is The Conversation's page counter tag. Please DO NOT REMOVE. --><img style="border: none !important; box-shadow: none !important; margin: 0 !important; max-height: 1px !important; max-width: 1px !important; min-height: 1px !important; min-width: 1px !important; opacity: 0 !important; outline: none !important; padding: 0 !important;" src="https://counter.theconversation.com/content/192702/count.gif?distributor=republish-lightbox-basic" alt="The Conversation" width="1" height="1" /><!-- End of code. If you don't see any code above, please get new code from the Advanced tab after you click the republish button. The page counter does not collect any personal data. More info: https://theconversation.com/republishing-guidelines --></p> <p><em>Writen by Samudyata and </em><em>Carl Sellgren</em><em>. Republished with permission from <a href="https://theconversation.com/long-covid-how-lost-connections-between-nerve-cells-in-the-brain-may-explain-cognitive-symptoms-192702" target="_blank" rel="noopener">The Conversation</a>.</em></p> <p><em>Image: Getty Images</em></p>

Mind

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Why do antidepressants help with nerve pain relief?

<div class="copy"> <p>Tricyclic antidepressants have long been known to have more than one purpose: among other things, they can alleviate pain – particularly nerve pain.</p> <p>Recent research has finally established <em>why</em> these tricyclic antidepressants (TCAs) can help with nerve pain. The discovery could lead to the rapid development of pain relief medications that don’t include the side effects of TCAs.</p> <p>Nerve pain comes from a variety of sources – including cancer, diabetes, trauma, multiple sclerosis, and infections. These treatments could address a range of different types of nerve pain.</p> <p>It turns out the drugs inhibit a key protein in our nerves, called an N-type calcium channel. These N-type calcium channels are shaped like tiny gates, allowing positively charged calcium ions, or Ca<sup>2+</sup>, through them. This helps with the transmission of pain signals in the body.</p> <p>Researchers have long been keen to find things that “close” the gate of these calcium channels because that’s likely to have analgesic effects.</p> <p>Adjunct Professor Peter Duggan, a researcher with the CSIRO and senior collaborator on the project, says that he and his colleagues initially stumbled across TCAs from a very different direction: they were investigating the toxins of venomous marine cone snails.</p> <p>“A few of the components in that toxin are actually painkillers and they block these calcium ion channels very, very effectively,” says Duggan.</p> <p>The cone snail toxin has the potential to be very dangerous to people, as well as needing to be administered in an impractical way, so the researchers started looking at similar compounds that might have some of the same properties.</p> <p>“What we’ve been doing is designing and making small molecules that mimic the activity of those kinds of toxins,” says Duggan.</p> <p>“One class that we looked at gradually trended towards the same structure as the tricyclic antidepressants.”</p> <p>Once they realised that TCA-like molecules could block these calcium channels, the researchers set out to look at TCAs specifically.</p> <p>Duggan’s collaborators at the University of Queensland set up a lab-based experiment with 11 TCAs and two drugs that are chemically very similar to TCAs.</p> <p>These 13 drugs were administered to <em>in vitro</em> neuroblastoma cells.</p> <p>“They’re (neuroblastoma) a type of brain cancer cell that naturally expresses the channel we’re interested in,” explains Duggan.</p> <p>Analysis of the cells by UQ, CSIRO and Monash University researchers showed that the drugs could all limit the amount of calcium that got transmitted through the cells. This means that these TCAs must alleviate pain by inhibiting the N-type calcium channel.</p> <p>A paper describing the work is <a href="https://doi.org/10.1039/D1MD00331C" target="_blank" rel="noreferrer noopener">published</a> in <em>RSC Medicinal Chemistry.</em></p> <p>Duggan says that there may be other mechanisms by which TCAs kill pain as well, and they definitely have other biochemical effects in the body. But it’s unlikely that the calcium channel-blocking is helpful in treating depression.</p> <p>TCAs are a very old and well-established form of antidepressant, and for treating depression, they’ve largely been replaced by newer drugs with fewer side effects.</p> <p>“They’re what we call ‘dirty drugs’,” explains Dr Michael Vagg, dean of the Faculty of Pain Medicine at the Australian and New Zealand College of Anaesthetists, and an associate professor at Deakin University.</p> <p>“They have effects on lots of transmitter systems and receptors in the body. They don’t have just the one straightforward action; they have multiple actions.”</p> <p>This means that TCAs typically have several side effects, including drowsiness, blurred vision and constipation.</p> <p>But because the researchers now have a specific understanding of how they alleviate pain, they can develop new drugs that don’t have these side effects.</p> <p>“The more we understand about how TCAs are causing the painkilling effect, the actual intimate mechanism of how they’re doing it, then there’s more chance of us being able to develop compounds that target that type of activity and not have other side effects or the other antidepressant effects,” says Duggan.</p> <p>Vagg is optimistic that better drugs are on the way. He cites the recent proliferation of new migraine treatments, which arrived less than a decade after researchers <a href="https://cosmosmagazine.com/health/migraine-masters/" target="_blank" rel="noreferrer noopener">found a similar key mechanism</a> in the brain, as his reasoning for this.</p> <p>He emphasises that it’s not yet a done deal – any new drug based on this research would still need to make it through the development pipeline and clinical trials.</p> <p>“I think because the tricyclic drugs are already widely used, and already seem to have – for most people – an acceptable level of safety, I suspect that means that development will go smoother rather than rougher,” says Vagg.</p> <p>This is good news for the roughly one in 20 Australians who suffer from nerve pain.</p> <p>“Nerve pain is highly disabling and ruins lives. The best current treatments only work to a useful degree on every third or fourth person who receives them,” says Vagg.</p> <p>“We have not had any really effective new treatments for nerve pain for a long time and this work opens up the possibility of designing a new class of drugs with improved safety and effectiveness.”</p> <p><em>Image credits: Getty Images</em></p> <p><em><!-- Start of tracking content syndication. Please do not remove this section as it allows us to keep track of republished articles --> <img id="cosmos-post-tracker" style="opacity: 0; height: 1px!important; width: 1px!important; border: 0!important; position: absolute!important; z-index: -1!important;" src="https://syndication.cosmosmagazine.com/?id=189966&amp;title=Why+do+antidepressants+help+with+nerve+pain+relief%3F" width="1" height="1" data-spai-target="src" data-spai-orig="" data-spai-exclude="nocdn" /> <!-- End of tracking content syndication --></em></div> <div id="contributors"> <p><em>This article was originally published on <a href="https://cosmosmagazine.com/health/medicine/tricyclic-antidepressants-nerve-pain-treatments/" target="_blank" rel="noopener">cosmosmagazine.com</a> and was written by Ellen Phiddian. </em></p> </div>

Mind

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Kate Middleton shows she has nerves of steel

<p><span style="font-weight: 400;">A day after <a rel="noopener" href="https://oversixty.com.au/entertainment/movies/royals-hit-the-red-carpet-at-bond-world-premiere" target="_blank">gracing the red carpet</a> premiere of </span><em><span style="font-weight: 400;">No Time To Die</span></em><span style="font-weight: 400;">, Prince William and Kate Middleton have made a <a rel="noopener" href="https://honey.nine.com.au/royals/prince-william-kate-middleton-duchess-of-cambridge-northern-ireland/3073b11b-6622-49c2-b939-55f4829b6e40" target="_blank">series of appearances</a> in Northern Island.</span></p> <p><span style="font-weight: 400;">During their first visit to Derry-Londonderry, the couple made a stop at the petting zoo on Ulster University’s Magee Campus, where Kate held a tarantula named Charlotte in the palm of her hand.</span></p> <p><span style="font-weight: 400;">“A surprise guest appearance from Charlotte the tarantula,” the Duke and Duchess of Cambridge wrote on social media.</span></p> <p><span style="font-weight: 400;">Prince William appeared less enthused and seemed to keep his distance from the arachnid in photos.</span></p> <p><span style="font-weight: 400;">He also joked that Kate’s bright purple suit prompted the spider to be unusually animated.</span></p> <p><span style="font-weight: 400;">“Maybe she’s not so keen on purple, or maybe she thinks you’re a flower,” he quipped.</span></p> <p><span style="font-weight: 400;">Instead, the Duke of Cambridge was spotted holding a snake, admitting that his eldest son would have loved it.</span></p> <p><span style="font-weight: 400;">“George is obsessed with snakes, he’s going to be so upset he missed this,” William said of the eight-year-old.</span></p> <p><span style="font-weight: 400;">The royal couple then made a stop at the Student Union, which was hosting a “Culture Shock” event, and sampled some local treats, as well as whiskey and Guinness.</span></p> <p><span style="font-weight: 400;">The Duke and Duchess then played a game with the students that saw them attempt to pronounce Irish words.</span></p> <p><span style="font-weight: 400;">“I’m going to have another drink, I’m not doing very well at this,” William joked.</span></p> <p><span style="font-weight: 400;">The pair also met with some nursing students they had spoken to earlier this year, then kicked a football around with City of Derry Rugby players, coaches, and volunteers involved in the Sport Uniting Communities initiative.</span></p> <p><em><span style="font-weight: 400;">Images: Getty Images</span></em></p>

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“It upset me”: Amanda Keller opens up about why Tom Gleeson’s Logies speech struck a nerve

<p>Amanda Keller has spoken out about comedian Tom Gleeson’s controversial Gold Logie win, and admitted that she was “upset” by parts of his speech.</p> <p>Gleeson, who hosts ABC’s <em>Hard Quiz</em> won the Gold Logie at the Logie Awards, after a satirical political style campaign as he targeted fellow nominees with short adverts outlining why he should win. No nominee was safe.</p> <p>It didn’t help that Gleeson ruffled feathers with his acceptance speech of the awards.</p> <p>“Just because all of you want it and I’ve got it, don’t get angry with me. It’s all right, you’ll all survive. It’s a shame this is the last Gold Logie that’s ever going to be handed out — according to Grant Denyer, I’ve ruined the Logies. But at least I won this all by myself,” he said according to <a rel="noopener" href="https://www.news.com.au/entertainment/awards/logies/amanda-keller-admits-tom-gleesons-gold-logie-speech-upset-her/news-story/cc5277821822a1fc1cba650e5efc21e5" target="_blank">news.com.au</a>.</p> <p>“Do you know what would have been weirder? If I campaigned for this award sincerely … Imagine me just sincerely saying I was humbled by the award. I wouldn’t be able to live with myself. It would make me want to vomit.”</p> <blockquote class="twitter-tweet" data-lang="en"> <p dir="ltr">Massive thank you to everyone who voted! Last night, I was mostly showing off to you at home. I really hope you got your money’s worth. Thank you again. <a href="https://twitter.com/hashtag/Gleeson4Gold?src=hash&amp;ref_src=twsrc%5Etfw">#Gleeson4Gold</a> <a href="https://t.co/N4d6tXNZky">pic.twitter.com/N4d6tXNZky</a></p> — Tom Gleeson (@nonstoptom) <a href="https://twitter.com/nonstoptom/status/1145583828703928320?ref_src=twsrc%5Etfw">July 1, 2019</a></blockquote> <p>Keller addressed the dig on the first Jonesy and Amanda show since the Logies, and admitted that while she understood the comedic angle, Gleeson made a joke about everyone who works hard in the television industry.</p> <p>“I think in his speech when he said, ‘everyone who works in TV, if you want to win this you’re a big wanker’, pretty much, and that upset me because he was mean to (last year’s Gold Logie winner) Grant (Denyer) I felt,” she told WSFM co-host Brendan “Jonesy” Jones. </p> <p>“He said, ‘Yeah I won it last year for Grant, and sucker, now I’ve done it on my own for me.’</p> <p>“That’s not fair to Grant, he won that last year on his own two feet. And people that have won in the past — Carrie Bickmore changed the world, she’s raised $10 million for brain cancer research. Grant spoke about redemption. Waleed Aly spoke about inclusiveness.”</p> <p>The day after he won, Gleeson was quick to assure everyone he doesn’t have bad blood with Keller. </p> <p>He said on <em>The Project</em>: <span>“She has a sense of humour — she would actually be offended by the idea that I felt sorry for her,” the comedian said.</span></p> <p>“So, I find it hard to do that because if I do, I’m denying her a sense of humour, and she was finding it funny.”</p> <p>However, Keller clarified her position on the Jonesy &amp; Amanda show , by saying that while she has “no problem with Tom”, she was still upset about some of his words.</p> <p>“I like Tom, we saw him at the airport, no problem with Tom. But (his speech) gave everyone permission to say, ‘yeah you’re all up yourselves, and this is all a big joke’. And it wasn’t a joke to me,” she explained.</p> <p>“I don’t know why in television we’re embarrassed to be proud of our work. The tourism industry has awards, the restaurant industry has awards … He got to a point where he said, ‘Sucko for wanting this, you know it’s all a dumb joke’ — and that’s what made me feel bad, because to the other nominees, it wasn’t.</p> <p>“We were all worthy, and I don’t think we should be embarrassed for being worthy.”</p>

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7 ways to calm those preflight jitters

<p>Nervous flyer? Use these tips for a smooth flight.</p> <p><strong>1. Get some sleep</strong></p> <p>All of your emotions are heightened when you’re tired and that applies to nerves too. In the lead up to your flight, make sure you’re well rested. Get to bed early for the few nights before or even try to sneak in a quick nap before take off. </p> <p><strong>2. Avoid caffeine</strong></p> <p>Caffeine can make you jittery at the best of times, so you’ll want to steer clear of it before a flight. It’s also known to increase anxiety, which isn’t a good idea if you’re already feeling nervous.</p> <p><strong>3. Get some exercise</strong></p> <p>Light exercise before a flight can put you in a better mindset and get your body feeling relaxed. Studies show that exercise can reduce anxiety also, preparing you mentally for the flight ahead.</p> <p><strong>4. Arrive early</strong></p> <p>The last thing you need is a terrifying dash through the airport five minutes before departure. Arrive at the airport nice and early so you can check in, go through security and be ready at the gate with plenty of time to spare.</p> <p><strong>5. Go easy on the booze</strong></p> <p>One drink can certainly put you in a more relaxed mood, but be careful not to drink too much. It can be very easy to knock back a few too many G&amp;Ts in the name of calming your nerves, yet it will ultimately have the opposite effect.</p> <p><strong>6. Pop a pill</strong></p> <p>If you’re really terrified at the thought of flying, medication might be the way to go. Explain the situation to your doctor and they will be able to prescribe you something to take the edge off.</p> <p><strong>7. Keep the window shade up</strong></p> <p>Once onboard, keep the window shade up so you can see outside. It will lessen any feelings of claustrophobia you might have from being inside the plane. Looking out at the world below can also be a beautiful distraction for when you need it.</p> <p>Are there any tips you would suggest? Let us know in the comments below.</p>

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Tips for travelling with people that get on your nerves

<p>Hey, of course we love our family and friends and nothing's going to change that. But sometimes when you're overseas this love is put to the test.</p> <p>Whether it's the fact that your brother refuses to leave the hotel or the fact that your best friend of 20 years has no idea what happened to those 200 Euros you lent her, there are moments where our loved ones can get on our nerves while holidaying.</p> <p>So what's the solution? Aside from running away from them in a crowded square, there are a number of measure you can take that can save your trip (and your relationships)!</p> <p><strong>Set expectations</strong></p> <p>Sometimes problems occur because people have different expectations for the trip. By making sure you and your travel buddies are aware of the sort of trip you'll be taking, you can generally get a sense as to whether there'll be any problems before you go.</p> <p><strong>Take the right approach to money</strong></p> <p>Money is often the biggest cause of conflict overseas. While it's important to make sure you're not being taken advantage of, at the same time you don't want to be too overzealous in your bookkeeping. There comes a point where you have to remember you're on holidays. A relaxed approach can make a big difference.</p> <p><strong>Divide rather than compromise</strong></p> <p>There’s going to be a point at your trip where you reach a fork in the road and you have to make a decision between doing one thing or another. Instead of compromising or choosing only one don’t be afraid to split up and each do what you want to do separately. It ensures you don’t miss out on what you really want to do, and gives each of you a story when you get back together.</p> <p><strong>Do what you’re best at</strong></p> <p>Good at reading maps? Then make sure you’re the person who’s doing the navigating. Encyclopaedic knowledge of exchange rates? Then make sure you’re the person who’s handling the money. Little things like this can ensure that you don’t waste any time caught up in activities that don’t cater to your talents and will generally save you from a bit of unnecessary passive aggression if you make some minor mistakes.</p> <p><strong>Roll with the punches</strong></p> <p>Things not going entirely as you planned? Well, it wouldn’t be the first time in the history of the world a holiday hasn’t gone to script. Instead of getting stressed out and taking the experience out on the people you're travelling with, take a deep breath and relax.</p> <p><strong>Related links:</strong></p> <p><span style="text-decoration: underline;"><em><strong><a href="/travel/travel-tips/2015/12/funny-way-to-avoid-losing-luggage/">One man’s genius way to avoid losing your luggage</a></strong></em></span></p> <p><span style="text-decoration: underline;"><em><strong><a href="/travel/travel-tips/2015/12/random-act-of-airport-kindness/">Stranger buys stranded traveller a flight to see her dying mother</a></strong></em></span></p> <p><span style="text-decoration: underline;"><em><strong><a href="/travel/travel-tips/2016/01/12-daggiest-tourist-photo-poses/">12 daggiest tourist photo poses</a></strong></em></span> </p>

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