Allergic reaction sparks award-winning science fair project for Missouri teen
Summary: The formation of prefrontal cortex dendritic spine formation sustains the remission of depressive related symptoms and behaviors following ketamine treatment by restoring lost spines.
Researchers have identified ketamine-induced brain-related changes that are responsible for maintaining the remission of behaviors related to depression in mice — findings that may help researchers develop interventions that promote lasting remission of depression in humans. The study, funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health, appears in the journal Science.
Major depression is one of the most common mental disorders in the United States, with approximately 17.3 million adults experienced a major depressive episode in 2017. However, many of the neural changes underlying the transitions between active depression, remission, and depression re-occurrence remain unknown. Ketamine, a fast-acting antidepressant which relieves depressive symptoms in hours instead of weeks or longer, provides an opportunity for researchers to investigate the short- and long-term biological changes underlying these transitions.
“Ketamine is a potentially transformative treatment for depression, but one of the major challenges associated with this drug is sustaining recovery after the initial treatment,” said study author Conor Liston, M.D., Ph.D., of Weill Cornell Medicine, New York City.
To understand mechanisms underlying the transition from active depression to remission in humans, the researchers examined behaviors related to depression in mice. Researchers took high-resolution images of dendritic spines in the prefrontal cortex of mice before and after they experienced a stressor. Dendritic spines are protrusions in the part of neurons that receive communication input from other neurons. The researchers found that mice displaying behaviors related to depression had increased elimination of, and decreased the formation of, dendritic spines in their prefrontal cortex compared with mice not exposed to a stressor. This finding replicates prior studies linking the emergence of behaviors related to depression in mice with dendritic spine loss.
In addition to the effects on dendritic spines, stress reduced the functional connectivity and simultaneous activity of neurons in the prefrontal cortex of mice. This reduction in connectivity and activity was associated with behaviors related to depression in response to stressors. Liston’s group then found that ketamine treatment rapidly restored functional connectivity and ensemble activity of neurons and eliminated behaviors related to depression. Twenty-four hours after receiving a single dose of ketamine, mice exposed to stress showed a reversal of behaviors related to depression and an increase in dendritic spine formation when compared to stressed mice that had not received ketamine. These new dendritic spines were functional, creating working connections with other neurons.
The researchers found that while behavioral changes and changes in neural activity in mice happened quickly (three hours after ketamine treatment), dendritic spine formation happened more slowly (12-24 after hours after ketamine treatment). While further research is needed, the authors suggest these findings might indicate that dendritic spine regrowth may be a consequence of ketamine-induced rescue of prefrontal cortex circuit activity.
Although dendritic spines were not found to underly the fast-acting effects of ketamine on behaviors related to depression in mice, they were found to play an important role in maintaining the remission of those behaviors. Using a new technology developed by Haruo Kasai, Ph.D., and Haruhiko Bito, Ph.D., collaborators at the University of Tokyo, the researchers found that selectively deleting these newly formed dendritic spines led to the re-emergence of behaviors related to depression.
“Our results suggest that interventions aimed at enhancing synapse formation and prolonging their survival could be useful for maintaining the antidepressant effects of ketamine in the days and weeks after treatment,” said Dr. Liston.
“Ketamine is the first new anti-depressant medication with a novel mechanism of action since the 1980s. Its ability to rapidly decrease suicidal thoughts is already a fundamental breakthrough,” said Janine Simmons, M.D., Ph.D., chief of the NIMH Social and Affective Neuroscience Program. “Additional insights into ketamine’s longer-term effects on brain circuits could guide future advances in the management of mood disorders.”
Nick Miller – NIH/NIMH
The image is in the public domain.
Original Research: Open access.
Liston, C. et al. “Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation”. Science. doi:10.1126/science.aat8078
Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation
The neurobiological mechanisms underlying the induction and remission of depressive episodes over time are not well understood. Through repeated longitudinal imaging of medial prefrontal microcircuits in the living brain, we found that prefrontal spinogenesis plays a critical role in sustaining specific antidepressant behavioral effects and maintaining long-term behavioral remission. Depression-related behavior was associated with targeted, branch-specific elimination of postsynaptic dendritic spines on prefrontal projection neurons. Antidepressant-dose ketamine reversed these effects by selectively rescuing eliminated spines and restoring coordinated activity in multicellular ensembles that predict motivated escape behavior. Prefrontal spinogenesis was required for the long-term maintenance of antidepressant effects on motivated escape behavior but not for their initial induction.
Ketamine is used for starting and maintaining anesthesia and induces a trance-like state while providing pain relief, sedation, and memory loss. It can cause confusion and hallucinations as it wears off. Discovered in 1962 it was used in the Vietnam War due to its safety and is on the WHO’s list of essential medicines.
It’s also used as a recreational drug in raves and as a club drug. Due to this, it’s a schedule III substance in the U.S.
That said, it’s been shown to limit borrelia in vitro: https://madisonarealymesupportgroup.com/2018/03/10/ketamine-limits-bb-in-vitro/
It’s also been shown to relieve her chronic pain, improve quality of life, reduce depression and suicidal ideation, and reduce opioid consumption: https://madisonarealymesupportgroup.com/2017/09/14/iv-ketamine-in-ptls/
This podcast features Jari Laukkanen, M.D., Ph.D., a cardiologist and scientist at the Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio. Dr. Laukkanen has been conducting long-term trials looking at the health effects of sauna use in a population of over 2,000 middle-aged men in Finland. The results? Massive reductions in mortality and memory disease in a dose-response fashion at 20-year follow-up. In this almost 25-minute episode, we talk about…
Further, Dr. Mary Shackelton, MPH, ND talks about skin as a pathway for detoxification and how important it is to sweat on a weekly basis. Infrared saunas are one of the most effective ways of releasing toxins from deep within one’s tissues.
https://madisonarealymesupportgroup.com/2018/01/03/the-invisible-universe-of-the-human-microbiome-msm/ Briefly, MSM stands for Methylsulfonylmethane and is 34% sulfur by weight. Sulfur plays a crucial role in detoxification and is an important antioxidant for producing glutathione. If you aren’t getting enough sulfur, glutathione can not work. Even if you have a diet rich in sulfur (think cabbage, onions, garlic, broccoli, etc – essentially the stinky veggies – and many other food items as well) your body still could use supplementation.
https://madisonarealymesupportgroup.com/2019/03/14/melatonin-benefits-uses/ Besides helping sleep, melatonin is known for protecting the brain. Research has shown starting to supplement in middle age protects against Alzheimer’s, reduces the risk of Parkinson’s, shrinks the size of the infarct area in a stroke, minimizes brain swelling & dysfunction after head injury, and increases the “longevity protein” SIRT1.
In certain regions of New York state, USA, Ixodes scapularis ticks can potentially transmit 4 pathogens in addition to Borrelia burgdorferi: Anaplasma phagocytophilum, Babesia microti, Borrelia miyamotoi, and the deer tick virus subtype of Powassan virus. In a prospective study, we systematically evaluated 52 adult patients with erythema migrans, the most common clinical manifestation of B. burgdorferi infection (Lyme disease), who had not received treatment for Lyme disease. We used serologic testing to evaluate these patients for evidence of co-infection with any of the 4 other tickborne pathogens. Evidence of co-infection was found for B. microti only; 4–6 patients were co-infected with Babesia microti. Nearly 90% of the patients evaluated had no evidence of co-infection. Our finding of B. microti co-infection documents the increasing clinical relevance of this emerging infection.
Sigh…..where to even begin
STAMFORD, CONN (April 12, 2019)—Global Lyme Alliance’s commitment to identify and fund innovative and promising Lyme disease research is unrivaled. A vital component to GLA’s leadership role in Lyme disease research is its success with early-stage funding. Discovering and supporting researchers who are new to Lyme but bring years of relevant disease work or are at the beginning of their careers, helps distinguish GLA’s approach to finding the evidence-based answers that will ultimately help patients.
In 2009, on a limited research budget, GLA had decided to proactively recruit scientists and fund research in new areas to further the understanding of Borrelia burgdorferi (the Lyme bacteria) that could lead to an improved diagnostic test and ultimately, a cure, for Lyme disease. GLA’s objectives were to:
Based on early findings of the Zhang/Johns Hopkins study that showed that the Lyme bacteria could ‘morph’ into persisters, GLA then recruited Kim Lewis, Ph.D., Director of the Antimicrobial Discovery Center at Northeastern University, who is an expert in the area of bacterial persistence and antibiotic tolerance. GLA worked with Dr. Lewis on developing a multi-year study design and agreed to fund it. This study would ultimately confirm the ability of Lyme organisms to become persisters and went on to then find existing and new drugs to kill these persister (non-growing) forms. Both Northeastern and Johns Hopkins were running parallel, independent experiments and drug discovery protocols backed by GLA.
By 2018, Dr. Ying Zhang and his team at Johns Hopkins made significant strides:
By 2018: Dr. Kim Lewis and his team at Northeastern University, independently, also made considerable findings:
The complete path from initial seed funding to results that will impact patients follows.
GLA Initial Seed Funding (2013)
GLA Annual Lyme Disease Research Symposium (2014)
Published Findings (2015): The Lyme bacteria morphs to evade antibiotics
GLA Fosters Collaboration & Continues Funding (2016, 2017, 2018)
Published Findings (2018): Vancomycin is the strongest antibiotic in treating Lyme disease
Clinical Trials & Helping Patients (2019)
Lyme disease is extremely complex, and the challenge to understand it and ascertain how to most successfully treat patients impacted by it is a herculean task. Through an aggressive and innovative research strategy, backed by a world-renowned Scientific Advisory Board and top-notch in-house science team, GLA is finding the answers.
About Global Lyme Alliance
Global Lyme Alliance is the leading 501(c)(3) organization dedicated to conquering Lyme and other tick-borne diseases through research, education and awareness. GLA has gained national prominence for funding some of the most urgent and promising research in the field, while expanding education and awareness programs for the general public and physicians. We support those around the globe in need of information about tick-borne diseases. Learn more at GLA.org.
Currently, Disulfiram is being used on numerous Lyme/MSIDS patients in Mexico and many more in the U.S. with pretty astounding results. The herxes can be surreal so it takes an experienced practitioner, but, it has action against malaria, HIV, cancer and Lyme (borrelia):
Do not self-treat. Talk to your practitioner about these findings and work with him/her. While Disulfiram (Antabuse) is cheap, it can cause vast die-off and an inflammatory response that could put you in the ER.
Lyme disease is primarily transmitted by ticks; that much most people know. The link between the words ‘Lyme’ and ‘ticks’ is cemented in the public consciousness, so much so that in 2018, many will instinctively conjure images of ticks when they hear or read something concerning Lyme disease. This is certainly progress. The enigmatic disease was only discovered a mere 43 years ago, although it has been around for centuries. Since its discovery in the town of Old Lyme, Connecticut, the disease has had a hard time being taken seriously, or at least being considered as the debilitating threat it undoubtedly is. Now that Lyme is finally becoming more visible in the mainstream medical community, patients and doctors alike are looking at ways it can be transmitted. One of the areas up for discussion is the possibility of sexual transmission.
Many severe and extreme conditions can be transmitted sexually, and everyone is aware of the dangers of prominent STDs like AIDS, HIV, syphilis, gonorrhoea and herpes. But could Lyme disease also join the line-up of threats? It was previously thought that any type of human-to-human Lyme transmission was impossible, and only specific types of tick could spread the disease. Borrelia burgdorferi is the bacteria responsible for causing Lyme; it’s carried by deer ticks in North America, and sheep ticks in Europe. It is estimated that as many as one in three ticks are contaminated with Borrelia, making the likelihood of catching Lyme in tick-populated areas quite high. Many people dismiss Lyme disease as they believe it’s easy to tell if you’ve been bitten by a tick or not. However, it is not altogether straightforward. Ticks will often seek out sheltered or hard-to-reach places on the human body before biting, and their saliva is laced with a paralytic agent that further minimises the risk of detection.
The appearance of a distinctive bullseye rash is one of the most concrete indicators of Lyme disease, although it can be quite hard to spot, and never appears in the first place in a minority of cases. This rash is accompanied by flu-like symptoms as the disease spreads in its acute stage. When these symptoms subside, the bacteria settle into the body, and the condition mutates into its chronic stage, which is notoriously hard to both diagnose and treat, and remains a point of contention between Lyme experts and other medical professionals. If the offending bacteria remains in a person’s system for many years, then it’s logical to assume that they can potentially transmit Lyme disease to their sexual partner(s) at any point during the prolonged infection. Therefore, it’s crucial to know if and how this type of transmission is possible.
According to the CDC (the Centres of Disease Control and Prevention), the case is crystal clear: their website officially states that ‘there is no credible scientific evidence that Lyme disease is spread through sexual contact’, going so far as to say that ‘the biology of the Lyme disease spirochete is not compatible with this route of exposure’. However, the CDC hasn’t got a great track history of Lyme expertise. Their position on the chronic form of Lyme is still a grey area at best, and their website also states that, in relation to the transmission of Lyme disease from mother to child during pregnancy, ‘no negative effects on the foetus have been found’. In fact, the transmission of Lyme during pregnancy is well-documented by Lyme experts and researchers, and although it’s a rare scenario, it is still possible.
So how do the experts see it? Dr. Carsten Nicolaus, head of Lyme specialists BCA-clinic in Augsburg, thinks that the question is not easily answered, and although it’s a probability, the risk seems very low. He cites a study conducted by Marianne Middelveen and Dr. Ray Stricker in 2014, which confirmed the presence of Borrelia burgdorferi in the genital secretions of Lyme-positive heterosexual couples. In one case, a couple was found to secrete an identical strain of Lyme spirochete in their separate samples, strongly indicating that the bacteria can be transmitted through unprotected sex. However, the study conducted is far too small to be of any diagnostic use; although the findings are interesting and alarming, more research and studies need be conducted to produce a concrete answer.
In theory, certainly, sexual transmission of Lyme disease is possible. The corkscrew-shaped Lyme spirochete shares many traits with Treponema pallidum, the microbe that causes syphilis. The latter is well-versed in the sexual transmission pathway, and has honed the method to near perfection. Borrelia has repeatedly been shown to be both opportunistic and insidious in the way it infects and survives in its host; it follows that if the opportunity for a new method of infection arose, it would almost certainly take it. As Lyme disease becomes more visible all over the world, it is important to remember that we know startlingly little about it, in comparison to other disorders. As such, it is crucial that meticulous study and tests continue, so we can rule out certain methods of transmission, or devise new ways to fight them.
Although this was written 4 months ago, it still demands an answer.
Isn’t it interesting that the small 2014 study barely raised eye-brows except for in the Lyme world? That should tell you something right away.
Authorities don’t want to know the answer to this question because first they’d have to admit stupidity & that they were wrong, and second, they’d have to do something about it….and heaven forbid either of those two things happen.
I’m quite open about the fact I believe I got this STD from my infected husband. All my initial symptoms were gynecological, it’s just I didn’t know anything about Lyme/MSIDS at the time. I went down the rabbit-hole of transmission fairly quickly in my journey due to my own case and I write about it, with tons of links to studies and experts disagreeing with the accepted narrative here: https://madisonarealymesupportgroup.com/2017/02/24/pcos-lyme-my-story/
Nothing is going to happen unless we demand it to happen. I find it highly interesting that at the first whiff of Zika being sexually transmitted, authorities followed through and it was the shot heard around the world – even though mosquitoes can’t even carry it in Wisconsin and many, many other states.
Here’s the map of places in the U.S. where the mosquitoes capable of transmitting Zika live:
Here’s where the black legged tick able to transmit Borrelia burgdorferi and B. mayonii (which cause Lyme disease), Anaplasma phagocytophilum (anaplasmosis), B. miyamotoidisease (a form of relapsing fever), Ehrlichia muris eauclairensis (ehrlichiosis), Babesia microti (babesiosis), and Powassan virus (Powassan virus disease) lives:
Here’s where the brown dog tick capable of transmitting Rocky Mountain spotted fever lives:
Here’s where the Gulf Coast tick capable of transmitting Rickettsia parkeri rickettsiosis, a form of spotted fever lives:
Tick distribution maps found: https://www.cdc.gov/ticks/geographic_distribution.html
In total – 7 types of ticks spreading deadly diseases in every single state in the U.S. but we know more about a tropical disease that in 80% of those who contract it have ZERO symptoms, and 1 out of 5 will have mild symptoms that last a week. https://madisonarealymesupportgroup.com/2016/12/21/how-zika-got-the-blame/. Call me crazy, but the disparity of risk between the two diseases couldn’t be greater.
Not to mention that migrating birds are transporting ticks worldwide:
I literally could go on and on with this….