"... Other researchers have also noticed the vagus nerve’s link between the gut and the brain. Around 2015, Mauro Costa-Mattioli and his colleagues at Baylor College of Medicine were investigating a link between a mother’s diet and the development of autism in her children when they inadvertently stumbled into gut microbiome research. 'Obesity is a big issue here in the US,' Costa-Mattioli explains. 'And there are epidemiological studies that actually showed that if the mom is obese, there is a higher possibility of the offspring developing autism.'
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![Brain-3.5.21[1]](https://i0.wp.com/costamattiolilab.org/news/wp-content/uploads/sites/6/2021/08/Brain-3.5.211.jpg?ssl=1 "Brain-3.5.21[1]")
In the News / Posted March 10th, 2021
BCM News: Microbes may hold the key for treating neurological disorders
"When we think about the causes of neurological disorders and how to treat them, we think about targeting the brain. But is this the best or only way? Maybe not. New research by scientists at Baylor College of Medicine suggests that microbes in the gut may contribute to certain symptoms associated with complex neurological disorders. The findings, published in the journal Cell, also suggest that microbe-inspired therapies may one day help to treat them."
"'We found that L. reuteri also can restore normal social behavior but cannot correct the hyperactivity in Cntnap2–/– mice,' said co-first author Dr. Shelly Buffington, a former postdoctoral fellow in the Costa-Mattioli lab and now an assistant professor at the University of Texas Medical Branch in Galveston."
"'We were able to separate the contribution of the microbiome and that of the animal’s genetic mutation on the behavioral changes,' co-first author Sean Dooling said. 'This shows that the gut microbiome shouldn’t be ignored as an important variable in studying health and disease.'"
In the News / Posted February 26th, 2021
Association for Psychological Science: The Gut and Brain, Inextricably Linked
"--Researchers are identifying the mechanisms involved in the brain-gut axis, laying the groundwork for more targeted interventions"
In research on ASD in animal models, Costa-Mattioli and colleagues found that treatment with the bacteria Lactobacillus reuteri—which reduces social deficits in mice that lacked those bacteria—appeared to work not by replenishing the mice’s gut microbiome but by promoting social-interaction-induced synaptic plasticity, which is impaired in ASD, through interactions with the vagus nerve (Sgritta et al., 2019). These findings support the groundbreaking idea that the gut microbiome can influence brain plasticity—and suggest that this type of research could point to novel therapies in human patients. However, the researchers cautioned that “the gut-microbiota-brain axis is an emerging field, and to ensure the success of microbial-based therapies for neurological disorders, we believe that first it would be important to establish a set of defined and objective criteria for transitioning into human clinical trials.”
Credit: Nik Spencer/Nature
In the News / Posted February 4th, 2021
Nature News Feature: How gut microbes could drive brain disorders
The paper from Dr. Martina Sgritta and her colleagues (Sean Dooling et al) was mentioned in this nice piece of summary of some highlights in studies investigating how the gut microbiota affect brain health.
"They tested L. reuteri in several other mouse models, and the bacterium was able to reverse some of the ASD-like behaviours in every one. And, just as with the Parkinson’s work, the researchers could block the effect in mice if they severed the vagus nerve.
Exactly what type of signal L. reuteri sends isn’t yet known. The team has found that some strains of L. reuteri can reverse the behaviours while others cannot, and the researchers are now working to discover which of its genes are involved. If they find the gene that produces a key metabolite, “we can just put it in any bacteria and now we may have a potential treatment”, Costa-Mattioli says. That strategy has yet to be tested.
One group in Italy is already trying L. reuteri as a therapy in 80 children with ASD. Participants will take L. reuteri or a placebo tablet for six months, and have their symptoms monitored. Costa-Mattioli is hoping to launch his own trial soon."
In the News / Posted April 24th, 2020
Science Perspective: Proteostasis dISRupted
Costa-Mattioli and Walter review the integrated stress response (ISR), a central signaling network that responds to proteostasis defects by tuning protein synthesis. (Read the review)
"The ISR is emerging as a promising avenue to reverse cognitive dysfunction in a wide range of memory disorders that resulted from disruption in protein homeostasis."
In the News / Posted Feburary 26th, 2020
Epilepsy Currents by American Epilepsy Society Commentary: mTORC2 Steals the Spotlight
"At first glance, the findings of Chen et al., 2019 may appear to contradict previous studies, in which treatment with the mTORC1-selective inhibitor rapamycin was able to both prevent and reverse abnormalities in brain size, behavior, and seizures in Pten conditional knockout mice. However, close reading of these articles reveals that the rapamycin dosing paradigms used resulted in not only inhibition of mTORC1 activity but also significant inhibition of mTORC2 activity. While short-term rapamycin exposure may selectively inhibit mTORC1, longer term exposure has been demonstrated to also inhibit mTORC2 activity, potentially through a reduction of mTOR availability for formation of the complex. ..."
Integrated Stress Response: A Molecular Switch Controlling Long-Term Memory in Down Syndrome
In the News / Posted January 7th, 2020
Cell Metabolism Preview: The Integrated Stress Response: A Central Memory Switch in Down Syndrome Author links open overlay panel
Genetic and pharmacological evidence causally demonstrate that the integrated stress response (ISR) is a central molecular switch for long-term memory formation across different species. Zhu et al. (2019) recently demonstrated that persistent activation of the ISR could explain the long-term memory and synaptic plasticity deficits in a mouse model of Down syndrome, the most common genetic cause of intellectual disability.
In the News / Posted December 28th, 2019
Included in Best of Neuron 2018 and 2019: Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder
The paper from Dr. Martina Sgritta and her colleagues (Sean Dooling et al) was one of the most widely read papers in 2019 and was selected by Neuron as Neuron Best of 2018-2019.
In the News / Posted December 26th, 2019
Apple News Science Blog: Restoring protein imbalance improves memory deficits in Down syndrome
Down syndrome is the most common genetic cause of intellectual disability. The disorder occurs when a person has three, instead of two, copies of chromosome 21. Currently, there is no effective treatment for this condition.
Memory deficits are a hallmark of Down syndrome, but little is known about the mechanisms that lead to them. In his lab at Baylor College of Medicine, Dr. Mauro Costa-Mattioli and his colleagues study at the cellular level mechanisms that are disrupted in Down syndrome looking to identify those that may be involved in causing the condition.
“In the current study, we investigated the role protein homeostasis networks play in Down syndrome. Protein homeostasis networks refers to the cell’s processes geared at maintaining a balance between how much protein is produced and how much is degraded, which is important for keeping cells working properly,” said Costa-Mattioli, professor of neuroscience and Cullen Foundation Endowed Chair at Baylor College of Medicine. “A decline in protein homeostasis networks is strongly linked to several neurological conditions, from aging to neurodegenerative disorders, but little was known about its role in Down syndrome.”
Costa-Mattioli and his colleagues discovered that activation of the ‘integrated stress response,’ or ISR, a network that regulates protein homeostasis by regulating protein synthesis, could explain the protein synthesis deficits associated with Down syndrome.
...
“Down syndrome mice exhibit problems with long-term memory,” said first author Dr. Ping Jun Zhu, assistant professor of neuroscience and senior investigator in the Costa-Mattioli group. “In one set of experiments we trained Down syndrome and control mice in a new task. Down syndrome mice did not learn the task as well as control mice. However, when we genetically or pharmacologically inhibited the ISR, the animals were able to learn almost as well as control mice.”
“In the last 10 years, we and others have shown the ISR is a molecular switch for normal long-term memory formation. In this study, we found that the switch is off in Down syndrome. More importantly, turning the switch back on in these mice reverses their memory deficits." Costa Mattioli said.
“These very encouraging results suggest that tuning the ISR may emerge as a promising avenue to alleviate a wide range of cognitive disorders with a disruption in protein homeostasis.”
In the News / Posted December 18th, 2019
Neuron Spotlight: Therapeutic Targeting of mTORC2 in mTORopathies
Dysregulated mTOR contributes to neurodevelopmental dysfunction. A new study (Chen et al., 2019) demonstrates that suppression of mTORC2, not mTORC1, ameliorates survival, seizures, and abnormal behaviors in a Pten mutant model, highlighting mTORC2 as a potential therapeutic target in mTORopathies.
Credit: Science Photo Library/Alamy Stock Photo
In the News / Posted December 4th, 2019
Nature Review Neurology Research Highlight: Integrated stress response mediates cognitive decline in Down syndrome
Down syndrome (DS), a neurodevelopmental disorder that results from the presence of an extra copy of chromosome 21, is a common cause of intellectual disability in the general population, but little is known about the molecular mechanisms that underlie the cognitive deficits. In a new study published in Science, Mauro Costa-Mattioli, Peter Walter and colleagues provide evidence that a signalling network known as the integrated stress response (ISR) mediates cognitive decline in DS.
“We hypothesized that loss of proteostasis — the process by which the cell’s proteins are monitored and maintained at homeostasis — could explain the memory deficits associated with DS,” comments Costa-Mattioli. “Protein synthesis is known to be required for long-term memory formation, and loss of proteostasis is associated with a wide range of cognitive and neurodegenerative disorders.”
...
Genetic or pharmacological inhibition of the ISR was found to restore protein synthesis and improve long-term memory in Ts65Dn mice. “We have previously identified that the ISR serves as a long-term memory switch, and in this study we found that the switch is off in DS,” explains Costa-Mattioli. “We showed that turning the switch back on by inhibiting the ISR reverses the cognitive decline associated with DS.”
The new findings raise the possibility that pharmacological manipulation of the ISR could help to alleviate cognitive impairments in individuals with DS. The investigators plan to further explore the mechanisms that lead to ISR activation in DS and to determine whether ISR inhibition can reverse cognitive deficits in other neurological conditions in which proteostasis is dysregulated.
Mice missing PTEN, a top autism gene, have bigger brains (right) than controls do (left).
In the News / Posted November 20th, 2019
Spectrum News Mouse study reveals overlooked target for autism therapies
The mice lack a gene called PTEN. Like many people who have a mutation in PTEN, the mice have enlarged brains, seizures and behaviors associated with autism. They also have hyperactive mTOR, a key enzyme in a pathway of the same name. The mTOR pathway is best known for its role in cancer; it governs cell growth and is hyperactive in several conditions related to autism.
The enzyme is part of two complexes called mTORC1 and mTORC2, each of which has a distinct function. Both complexes are known to be hyperactive in people with a PTEN mutation and in mice missing the gene.
However, the new study suggests that mTORC2 is solely responsible for the mice’s seizures and unusual behaviors.
The findings come as a surprise because many other studies pointed to mTORC1 as the main culprit, says lead investigator Mauro Costa-Mattioli, chair of neuroscience at Baylor College of Medicine in Houston, Texas.
In the News / Posted November 20th, 2019
Neuron Featured Article Preview: NMD Takes the Immune Road to NDD
Proper mRNA quality control prevents immune activation; when it goes awry, mice and flies develop abnormal behavioral phenotypes. In this issue of Neuron, Johnson et al. (2019) report that inhibiting nonsense-mediated mRNA decay (NMD) contributes to the pathogenesis of neurodevelopmental disorder (NDD) phenotypes by triggering aberrant immune activation.
In the News / Posted November 15th, 2019
Science Perspective: Translating translation in Down syndrome.
Across the spectrum of neurological disorders, from the developmental to the degenerative, clinical features and progression are influenced not only by disease-specific genetic effects but also by more generic mechanisms. Dysregulated stress responses are emerging as common targets for therapeutic intervention independently of causal genes, offering the tantalizing prospect of new treatments for a swathe of diseases irrespective of specific etiology. The integrated stress response (ISR) is a key player in the control of proteostasis—the balance between protein synthesis and degradation that is essential for cellular health. Dysregulated proteostasis is a common feature of the neuropathological landscape, from fragile X syndrome (1) to the neurodegenerative disorders Alzheimer's and Parkinson's diseases (2). On page 843 of this issue, Zhu et al. (3) provide compelling evidence that Down syndrome (DS), the most common genetic cause of intellectual disability, joins the pantheon of neurological disorders in which dysregulated ISR signaling plays a key role.
In the News / Posted October 31st, 2019
A no-nonsense treatment for autism spectrum disorder
Mutation of the nonsense-mediated mRNA decay factor Upf2 leads to neurological phenotypes that can be corrected with immunosuppressive drugs in mice.
Many genetic mutations implicated in autism spectrum disorder (ASD) are in regulators of mRNA expression, processing, and translation. Among these, copy number variants of the UP-frameshift 2 (UPF2) gene that regulates nonsense-mediated mRNA decay (NMD) have been identified in patients with ASD. NMD is responsible for degrading mRNAs with a premature stop codon, an essential quality control mechanism limiting the creation of nonfunctional proteins. In Johnson et al., researchers identified new UPF2 variants in patients with language disorder and intellectual disability and investigated the impact of Upf2 mutation in mouse and fly models.
This study provides further understanding of how genetic mutations impacting mRNA and protein processing could lead to the behavioral changes associated with ASD. In the case of UPF2 mutations, the pathological driver may be an increased activation of the brain immune system that can be targeted by immunosuppressive drugs. Now researchers can investigate whether mutations in other NMD regulators result in similar neurological impairments and whether an immunosuppressive strategy is effective in treating patients with these mutations. A limitation of the study is the neuron-specific deletion of Upf2 in the mouse model, which does not directly match the global expression of UPF2 variants in patients. Nevertheless, this study exemplifies the importance of investigating expression regulators, such as Upf2, to determine how behavioral phenotypes arise and to identify molecular changes that can be corrected by therapeutic intervention.
In the News / Posted October 21st, 2019
New therapeutic strategy may help PTEN mutation symptoms
Autism is a developmental disorder that affects 1 in 59 children in the U.S. Mutations in specific genes, such as PTEN, can explain many autism cases. While children with mutations in PTEN exhibit autism, macrocephaly (an abnormally large skull), intellectual disability and epilepsy, there are currently no effective treatment options for those affected by this condition. But a new study by researchers at Baylor College of Medicine offers a potential new approach to therapy.
Published today in Nature Medicine, the study showed that a previously unexplored pathway goes awry in the brain of PTEN-deficient mice, and its restoration reverses their behavioral and neurophysiological abnormalities. More importantly, the researchers developed a new therapeutic strategy to treat the symptoms associated with PTEN-deficiency in this mouse model.
“PTEN is associated with the mTOR signaling pathway, which includes two distinct molecular complexes — mTORC1 and mTORC2 — each one regulating different cellular functions,” said first author Chien-Ju Chen, a graduate student in the lab of corresponding author Dr. Mauro Costa-Mattioli, professor of neuroscience and Cullen Foundation Endowed Chair at Baylor College of Medicine.
“We found that genetically silencing the mTORC1 complex in PTEN-deficiency mice only resulted in restoration of the size of the brain. It did not affect survival, the behavioral alterations or even the number seizures. Unexpectedly, genetically silencing mTORC2 complex activity resulted in prolonged lifespan, suppressed seizures, rescue of long-term memory and reduced autism spectrum disorder-like behaviors,” Costa-Mattioli said.
Currently, there is no drug that could specifically inhibit mTORC2. Thinking of possible future clinical applications of these findings, the researchers developed an antisense oligonucleotide, a molecule that silences the activity of mTORC2 by preventing the synthesis of one of its defining components.
“Amazingly, when we administered a single injection of the anti-sense oligonucleotide, we were able to reverse the abnormal behaviors and reduce seizures in Pten-deficient mice,” Chien-Ju Chen said.
These findings are important because research efforts have mainly been focused on developing drugs to modulate mTORC1. Costa-Mattioli and his colleagues found that brain size and behavior are regulated by different mTOR complexes and molecular processes. More importantly, they found that mTORC2 is the major driver of the behavioral and other neurological alterations in PTEN-deficient mice, and their findings suggest that modulation of mTORC2 activity is a promising therapeutic approach.
Finally, mTOR signaling also is altered in other neurological disorders, including epilepsy, tuberous sclerosis, Fragile X syndrome and Alzheimer disease. Future experiments should determine whether mTORC2 also is the main mTOR complex implicated in these disorders.
Other contributors to this work include Chien-Ju Chen, Martina Sgritta, Jacqunae Mays, Hongyi Zhou, Rocco Lucero, Jin Park, I-Ching Wang, Jun Hyoung Park, Benny Abraham Kaipparettu, Loredana Stoica, Paymaan Jafar-Nejad, Frank Rigo, Jeannie Chin and Jeffrey L. Noebels.
In the News / Posted October 1st, 2019
Study reveals a new pathway, a potential treatment for neurological disorders
Many individuals with neurodevelopmental disorders, such as autism spectrum disorder and intellectual disability, suffer from these mental conditions without knowing the specific cause. In a multidisciplinary study, researchers at Baylor College of Medicine have revealed how dysfunction in a key quality control mechanism leads to neurological dysfunction in humans, mice and files.
Their findings, published in the current edition of Neuron, show that inhibition of nonsense-mediated decay (NMD) cause brain inflammation, and more importantly, that two FDA-approved drugs were able to help reverse the neuronal and behavioral deficits in NMD-deficient animals.
“We modeled this in mice lacking Upf2 and saw that not only did they have impaired NMD, but also memory, social and communication behavior deficits, similar to the patients,” said Dr.Jennifer Johnson, a former graduate student in the MCM lab at Baylor College of Medicine. “The function of Upf2 in the brain seems to be evolutionarily conserved because investigators also showed that flies lacking Upf2 showed memory problems.”
Because the human patients showed language problems, Yuwei Liu, a current graduate student in Costa-Mattioli’s lab, studied ultrasonic vocalization, a behavior that’s thought to reflect a type communication in mice, and discovered that mice lacking Upf2 exhibit altered vocalization patterns.
The investigators are excited with their results because they might have discovered a new pathway implicated in speech and language function and even and new way to treat speech disorders.
However, before discussing the possibility of doing experiments in humans, Costa-Mattioli and his team wish to know how disruption in NMD leads to an activation of the immune response, and, when the immune system is dampened using drugs, what communication is taking place on the molecular level that then improves or reverses behavioral deficits.
“We were totally surprised when we found that there was a significant increase in the total number of immune cells in the brain of the mice lacking Upf2,” said Dr. Loredana Stoica, a former graduate student in the lab of Costa-Mattioli.
“The importance of NMD as a key regulator of gene expression required for proper brain function is largely unappreciated,” Costa-Mattioli said. He also wonders whether NMD is implicated in normal aging or other major neurological disorders like Alzheimer’s disease.
While it is far too early to know if these two FDA approved drugs could be quickly repurposed for the treatment of brain disorders with deficient NMD, it remains an interesting possibility.
An interpretation piece published in one of the biggest Chinese online scientific community BioArt: Understanding the role of NMD in the central nervous system
In the News / Posted October 15th, 2019
In our third episode, Dr. Mauro Costa-Mattioli, the Director of the Memory and Brain Research Center at Baylor College of Medicine, gives us his thoughts on memories and microbes as well as the approaches he uses to push forward into new scientific fields.
In the News / Posted August 6th, 2019
Scientific wandering led by serendipity:
From microbiology to memory to microbial-driven behaviors — "The best is yet to come".
In the third episode of The Gastronaut Podcasts, <Debugging Our Memories>, Dr. Mauro Costa-Mattioli, the Director of the Memory and Brain Research Center at Baylor College of Medicine, gives us his thoughts on memories and microbes as well as the approaches he uses to push forward into new scientific fields.
0:12:30 Peter (the host): "What prompted you to go into the microbiome field from being very heavily focused on memory to studying the microbiome?" MCM: "I would say serendipity. So the project we started actually aimed to look at how diet could affect behaviors..."
0:20:40 MCM's advice to entering graduate students: 1,Trust no one; be vocal when needed. 2, Be curious; take your own initiative. 3, Never get discouraged; PhD training is a marathon, but not a sprint. 4, Learn to fail. 5, Take your project/experiments seriously; "give your experiment a chance to be successful".
"...From the moment you have a story that is strong and you believe in it, this is where your PhD starts."
0:27:50 MCM's advice to starting investigators: "Instead of worrying of getting more funding upon starting the lab, instead you should focus on doing your science/enjoy your science, if the science/experiment is good, it will bring money, and the money should support more science, which will bring more money... From the moment that you're in the cycle, it's nonstop. The first several years when you're not yet in the cycle, don't get into it until you need to..." "I understand the pressure is massive. The funding is actually getting low. The funding agencies like NIH or the government should increase/keep up with the support in science..."
“From memories to microbes, we’ve got the chance to see how Dr. Costa-Mattioli has not let himself be defined by one particular field. It was the refusal to let go of an interesting finding that sparked his curiosity that has made it easy for him to push forward into new fields. I feel like we should take this mentality and try invest a little bit of time every month to reflect on what excites us about what we do. Perhaps even write it down or share it with someone. If nothing comes to mind, maybe it’s time to rethink our approach to our work.”
In the News / Posted June 26th, 2019
Supplements, worms and stool: How families are trying to game the gut to treat autism traits
Scientists are playing catch-up as microbiome-based treatments for autism proliferate.
"....About 19 percent of physicians surveyed in 2009 said they recommend probiotics to the autistic people they treat. An unpublished survey of 100 people found 2 adults trying stool transplants at home for autism.
These unregulated therapies can be costly and unpredictable — and they pose significant, even life-threatening, risks. Home-grown stool transplants and parasites, for example, can introduce deadly infections. This month, the U.S. Food and Drug Administration issued a safety alert about fecal transplants after two recipients contracted an antibiotic-resistant infection and one of them died.
Given the public’s interest in these therapies, researchers should “speed up the process, as far as investigating and understanding why,” says Chiazotam Ekekezie, who led the survey of 100 people when she was chief medical resident at Rhode Island Hospital at Brown University. 'Rather than [have] people taking it into their own hands, maybe we can standardize it and make access equitable and safe.' "
...
"The mechanisms involved in brain-gut communication are many and layered. The vagus nerve, for example, connects the brainstem to the visceral organs; signaling molecules in the immune system, as well as hormones and neurotransmitters, can all modulate messages traveling back and forth. Costa-Mattioli has focused on a single species of gut bacteria, Lactobacillus reuteri, found in yogurt and commercial probiotics. In 2016, his team found that these bacteria seem to restore sociability in pups born to obese mice.
In a follow-up study last year, the team tested L. reuteri in three mouse models raised without a microbiome. Again the bacteria restored the mice’s social behaviors — but only under certain conditions. 'We were very surprised to find that when we cut the vagus nerve, the bacteria were no longer able to reverse the social deficits,' Costa-Mattioli says. The mice also did not respond if the researchers knocked out the oxytocin receptors in the brain. Costa-Mattioli speculates that L. reuteri produces a metabolite that activates the vagus nerve to promote oxytocin, the ‘cuddle hormone.’ This hormone then turns on the brain’s reward center for social behavior. Impeding the message at any point along this relay — from bacteria to metabolite to vagus nerve to oxytocin receptors — impairs the animals’ sociability, but Costa-Mattioli points out that other microbes may also produce this same factor or metabolite."
Source: Adapted from Front. Integr. Neurosci. 2013, DOI: 10.3389/fnint.2013.00070.
In the News / Posted April 8, 2019
How your gut might modify your mind
The microbes that live in your body might be influencing your behavior. Researchers want to know what they’re saying to your brain and how.
'To make a long story short, what we discovered is that the maternal diet eliminates a particular bacterium, Lactobacillus reuteri, in the offspring', Costa-Mattioli explains. Reintroducing the bacterium, either by intervention from the scientists or by the mice eating poop, reverses the social deficit. The scientists also found that the bacterium sends signals from the gut to the brain via the vagus nerve, increasing production of the hormone oxytocin, which promotes social bonding (Cell 2016, DOI: 10.1016/j.cell.2016.06.001). ..."
In the News / Posted April 2, 2019
Can this mouse treat Autism?
“In this research, we determined that the vagus nerve and the oxytocin-dopamine reward system were both necessary for the social behaviors to be restored,” explained Martina Sgritta, a postdoctoral associate in the Costa-Mattioli lab at Baylor. “When we cut the vagus nerve, the treatment with the bacteria had no effect. When we prevented the oxytocin to bind to its receptors in the specific brain area involved in social reward, the bacteria was not able to have an effect either. So L. reuteri needed both the vagus nerve and the oxytocin receptors to restore the behavior.”
That deeper understanding of the mechanisms involved plays a critical role in analyzing exactly how the bacteria restored social behaviors in the mice models, since increased levels of oxytocin—also known as the “love hormone”—are related to a boost in sociability.
In the News / Posted January 28, 2019
Germs in Your Gut Are Talking to Your Brain. Scientists Want to Know What They’re Saying.
"...To study autism, Dr. Mauro Costa-Mattioli and his colleagues at the Baylor College of Medicine in Houston investigated different kinds of mice, each of which display some symptoms of autism. A mutation in a gene called SHANK3 can cause mice to groom themselves repetitively and avoid contact with other mice, for example. ..."
"...Dr. Costa-Mattioli found evidence that L. reuteri releases compounds that send a signal to nerve endings in the intestines. The vagus nerve sends these signals from the gut to the brain, where they alter production of a hormone called oxytocin that promotes social bonds. ..."
In the News / Posted December 20, 2018
Can autism be treated with a simple microbial-based therapy?
"... The dream of this unconventional approach is that we would be using this or a similar microbial-based treatment. This particular bacterium, for instance, is considered safe in people and it was already given to infants to treat colic. There are no secondary effects and there is no toxicity. It is non-invasive and, perhaps, could someday just be added to yogurt—or taken in a pill form or, perhaps, with water. It is still extremely early to envision this, but if this were to be true, I think not only will we have to change the way we think about the disease, but also new treatments. Because you’re treating the brain through the gut, which, a few years ago, was sort of unthinkable. But now, it might become a reality. ..."
In the News / Posted December 6, 2018
Gut bacteria may offer a treatment for autism - A common probiotic holds the key
"...The crucial aspect of this work is L. reuteri’s wide availability—an availability approved by regulators such as America’s Food and Drug Administration. This existing approval, which means L. reuteri poses no known health hazard, simplifies the process of organising clinical trials.
Clearly, autism in people is more complicated than a mere willingness to associate with others. And getting too excited about a mouse trial is usually a mistake. But in Dr. Costa-Mattioli’s view his results, which have been replicated in part by Evan Elliot’s laboratory in Bar-Ilan University, Israel, would justify embarking on at least preliminary trials intended to determine whether L. reuteri has positive effects on people with autism, and might thus be worth pursuing. ..."
In the News / Posted August 17, 2017
Khatiwada: Funding uncertainty threatens addiction research
"...As a Ph.D candidate at Baylor College of Medicine, my research seeks to develop a deeper understanding of the brain, including identifying risk factors that make some individuals more susceptible than others to the effects of addictive drugs. These advancements, which will assist in the development of novel therapeutic approaches to prevent drug addiction, are contingent upon robust federal funding of keystone agencies, including the National Institutes of Health (NIH) and the National Science Foundation (NSF).
Recognizing the critical importance of supporting scientific research, Congress has expressed opposition to the substantial cuts to NIH and NSF proposed in the president's fiscal year 2018 budget. Although House lawmakers are showing support for NIH in their draft funding bill, they have proposed cuts to NSF. Any cuts to research would have widespread repercussions, including delayed progress toward life-saving medical advancements. ..."
In the News / Posted July 25, 2016
A single species of gut bacteria can reverse autism-related social behavior in mice
"...In particular, the researchers believe that their work, which uses a human-sourced bacterial species to promote oxytocin levels and improve social behavioral deficits in deficient mice, could be explored as a probiotic intervention for the treatment of neurodevelopmental disorders in humans.
'This is where the science is unexpectedly leading us. We could potentially see this type of approach developing quite quickly not only for the treatment of ASD but also for other neurodevelopmental disorders; anyway, this is my gut feeling,' Costa-Mattioli says. ..."
In the News / Posted June 18, 2016
Gut feelings - The theory that bacteria are involved in some cases of autism gets a boost
ONE of the less-known problems of obesity is that obese mothers are 50% more likely than those of normal weight to give birth to children who go on to develop autism. This correlation is perplexing, but some suspect it is connected to differences between the gut bacteria of the overweight and of those who are not. One researcher who thinks this way is Mauro Costa-Mattioli of Baylor College of Medicine, in Houston. He has just published evidence in Cell that, in mice at least, a clear relationship does exist between gut flora, obesity and social behaviour. What is particularly intriguing is that the culprit seems to be a single bacterial species.
Dr Costa-Mattioli and his colleague Shelly Buffington set up a series of experiments, each of which involved feeding 100 female mice a normal diet or a high-fat diet for eight weeks, getting those mice pregnant and then examining both the behaviour and the gut flora of their offspring. To monitor behaviour, the researchers put the pups through tests that measured how long they spent interacting with strangers and with inanimate objects. To study the gut floras, they used a test called ribosomal-RNA sequencing to identify which species the animals’ faeces contained.
In the News / Posted Feburary 1, 2015
Mauro Costa-Mattioli: Memory’s Puppeteer
"...During Mauro Costa-Mattioli’s childhood in rural Uruguay, the government was transitioning from fascism to democracy. “At the time it was very difficult to pursue science,” he says. Yet he fell in love with biology, and throughout his elementary school years, as a military government ruled the country, Costa-Mattioli spent his time dissecting plants and animals and staring into a microscope. He continued to study microbiology as an undergrad at the University of the Republic in Montevideo, and when he saw the opportunity to go abroad to pursue graduate work, Costa-Mattioli left for France to study the genomic strategies viruses deploy to escape immune attack. ..."
"...Upon relocating to Canada, Costa-Mattioli heard a talk by Nobel laureate Eric Kandel discussing the as-yet-unknown role of protein synthesis in memory formation. Costa-Mattioli was intrigued and decided that working out the mechanisms of such a phenomenon would help him carve out a niche in the translation world. “And I was in the best lab in the world to develop this project,” he says. The only problem? “We didn’t know anything about neuroscience,” adds Sonenberg.
Costa-Mattioli was not deterred. He reached out to experts to get training in behavior, neurobiology, and electrophysiology, and in 2005, he, Sonenberg, and colleagues provided genetic evidence that protein synthesis is necessary for long-term memory in mice. They then showed that this process is governed by the phosphorylation of a translational regulator, eIF2α; reducing phosphorylation enhanced memory in mice, and ramping it up impaired memory. 'It was amazing to see: you change a particular amino acid, and you make an animal smart. Or you do the opposite and make it stupid,' Costa-Mattioli says. 'That is the power of biology.' ..."
In the News / Posted June 21, 2014
Key process required to weaken strength of synaptic connections, store memory identified
Pictured are the authors for the Nature Neuroscience Paper: Dr. Gonzalo Viana Di Prisco, assistant professor; Wei Huang, graduate student; Dr. Shelly A. Buffington, postdoctoral fellow, all in the department of neuroscience.
In a study published in Nature Neuroscience, researchers at Baylor College of Medicine have identified a new model by which LTD – and related behaviors – is generated, opening the door to creating new avenues toward treatments for many neurological conditions.
“We knew that long-term depression (LTD) required the synthesis of new proteins but we didn’t know how the process was regulated or the identify of the newly synthesized proteins. Our study identifies the precise mechanism by which LTD occurs,” said Dr. Mauro Costa-Mattioli, associate professor of neuroscience at Baylor and senior author on the study.
“We found that the translation factor elF2a tightly controls the induction of LTD; reduction of eIF2a activity blocks LTD while its induction triggers LTD,” said Dr. Gonzalo Viana Di Prisco, assistant professor of neuroscience at Baylor and a lead author on the study.
In the News / Posted April 24, 2014
Baylor College of Medicine celebrates $100 million in Albert and Margaret Alkek Foundation grant funding.
Symposium highlight:
"...Dr. Mauro Costa-Mattioli, associate professor of neuroscience. Costa-Mattioli has discovered key signaling pathways that are required for the formation of long-term memory. He is a recipient of an Alkek Award for Pilot Projects in Experimental Therapeutics, a college-wide seed fund to build Baylor expertise and capacity in target validation as well as in preclinical translational research focused on the development of promising therapeutic targets, devices or diagnostic tools. ..."
The winners include Dr. Mauro Costa-Mattioli, assistant professor neuroscience; Dr. Martin Matzuk, professor of pathology & immunology; Dr. Jeffrey Noebels, professor of neurology; Dr. Matthew Rasband, professor of neuroscience, and Dr. Thomas "Trey" Westbrook, professor of biochemistry and molecular biology and molecular and human genetics.
In the News / Posted July 12, 2013
Five DeBakey Excellence in Research Award winners showcase breadth of Baylor College of Medicine research.
Five scientists whose recent research demonstrates the breadth and depth of basic science at Baylor College of Medicine received the 2013 Michael E. DeBakey Excellence in Research Award, named in honor of the College’s first president, in ceremonies today.
" In his most recent paper in Nature Neuroscience, Costa-Mattioli and colleagues discovered that by regulating actin polymerization, the recently discovered mTORC2 complex links structural changes in the neuron that contribute long-term changes required for memory storage. This paper, the first in the memory field to combine mouse and fly genetics, show that mTORC2 decides whether a long-term memory will be stored in the brain. In addition, they have found a small molecule that promotes mTORC2 activity and acts as a "memory-enhancing drug.” Hence, mTORC2 could be a novel therapeutic target for the treatment of cognitive dysfunction."
"... 'To briefly indicate the level at which this work has penetrated the popular consciousness, it has become an answer on the long-running TV game show Jeopardy! for $1,200, 'M. Costa-Mattioli found a protein that controls memory formation, a possible help for this disease named for a German,'' wrote Dani. ..."
Jeopardy / Archived Jan 5, 2012
The answer is...
In the News / Posted May 4, 2013
Novel storage mechanism allows command, control of memory
Introductions at a party seemingly go in one ear and out the other. However, if you meet someone two or three times during the party, you are more likely to remember his or her name. Your brain has taken a short-term memory - the introduction - and converted it into a long-term one. The molecular key to this activity is mTORC2 (mammalian target of rapamycin complex 2), according to researchers at Baylor College of Medicine in an article that appeared online in the journal Nature Neuroscience.
"Memory consolidation is a fundamental process," said Dr. Mauro Costa-Mattioli, assistant professor of neuroscience at BCM and corresponding author of the report. "Memories are at the center of our identity. They allow us to remember people, places and events for a long time, even a lifetime. Understanding the precise mechanism by which memories are stored in the brain will lead to the development of new treatments for conditions associated with memory loss".
In the News / Posted December 19, 2011
“Super memory” pill–and possibly an Alzheimer’s cure–could be around the corner
Scientists have isolated a gene in mice that works to give them "super memories" and reverses the course of several degenerative mental illnesses like Alzheimer's. And because of the similarity of mice and human brains, a powerful brain pill for humans may now not be far off.
The brains of both mice and humans release a gene known as PKR, which is triggered by the onset of Alzheimer's. But the newly discovered gene can apparently block PKR's release--a development that not only can reverse the course of degenerative brain diseases such as Alzheimer's, but induces a state of "super memory" in the mice it has been tested on.
"If we were to find an inhibitor, a molecule, a drug that will specifically block PKR, we should be able to do the same [in humans]," Maura Costa-Mattioli, who led the research study at Baylor College of Medicine, told the Vancouver Sun. "And we did."
In the News / Posted February 11, 2011
Pharmacogenetics reveal key memory protein complex.
Researchers from Baylor College of Medicine have provide the first direct genetic evidence that a complex of proteins known as mammalian target of rapamycin complex 1 (mTORC1) plays a crucial role in memory formation.
The findings, which could have implications in treating those suffering from post traumatic stress disorder and a wide range of cognitive memory disorders, can be found in the current edition of the Proceedings of the National Academy of Sciences.
"In the study we use a drug called rapamycin. We have known that this drug could reduce brain activity that strengthens long-term memory and can partially block long-term memory,"said Dr. Mauro Costa-Mattioli, assistant professor of neuroscience at BCM and the senior author of the study. "However the effect of the drug could be non-specific. In addition, the evidence that mTORC1 promotes long-term memory and enhances the connection between brain cells has been controversial."
In the News / Posted November 6, 2008
Mauro Costa-Mattioli was awarded the Eppendorf and Science Prize for Neurobiology.
"2008 Grand Prize winner: Mauro Costa-Mattioli for his essay "Switching Memories ON and OFF."
DR. Costa-Mattioli received his bachelor's degree in biology from the University of the Republic, Montevideo, Uruguay. In 1998, he was offered an opportunity to continue his studies in France, where he received his master's degree (diplôme universitaire) from Pierre and Marie Curie University, Paris, and his Ph.D. from the University of Nantes under the supervision of Sylviane Billaudel. During his graduate work, he studied genetic variability of positive-stranded RNA viruses. In 2002, he joined the laboratory of Nahum Sonenberg at McGill University, Montreal, as a postdoctoral fellow. His work defined the role of translational (protein synthesis) control in long-lasting synaptic plasticity and memory formation. In the summer of 2008, he joined the faculty at Baylor College of Medicine in Houston, Texas, as an assistant professor of neuroscience. Using multidisciplinary approaches, Dr. Costa-Mattioli's laboratory studies the molecular and cellular mechanisms underlying long-term synaptic plasticity, learning and memory, and related neurological disorders."
Switching Memory ON and OFF.
by Mauro Costa-Mattioli.
"...Ireneo Funes, the fictional main character in Jorge Luis Borges' short story “Funes el Memorioso,” could remember in vivid detail every day of his life after he was thrown from a wild horse at a ranch in Fray Bentos, Uruguay. He had acquired a prodigious ability to store new information without any practice. Unlike Funes [and real 'autistic savants'], who could store information with a glance, most people learn new things only after many attempts. ..."
"...If making new proteins is the rate-limiting step required to store new long-lasting memories, how is this process turned on? If one were able to identify the triggering mechanism and switch it on, then stimulation normally eliciting short-lasting changes should evoke long-lasting ones. Could an increase in the ability to make new proteins explain extraordinarily long-lasting memories? ..."
"... As 'Ireneo Funes died in 1889', we shall never know whether eIF2α activity was exceptionally low in his brain; however, it remains a possibility. ..."
Courtesy of Nahum Sonenberg/McGill University.
In the News / Posted September 3, 2007
Hold That Thought.
"... WHEN WAS THE LAST TIME you misplaced your car in a parking lot? Gave you a bit of a scare, didn't it? What about when you blanked on the name of a longtime friend—did you wonder if you were showing the first signs of Alzheimer's disease? These are not trivial fears. Memory is as vital to your trip to the grocery store as it is to your role at work and to your very personality. ..."
"...Researchers have discovered multiple genetic and pharmacological techniques to improve memory, an accomplishment that will no doubt capture the attention of an aging population (see page 22). They have also determined what happens when memory malfunctions. These findings could one day enable physicians to cure learning disabilities or to erase the unbearable memories associated with posttraumatic stress disorder. ..."
in lab vs in news @ McGill 2007
Dr. Mauro Costa-Mattioli is one of the researchers at McGill University who have discovered a gene which improves the memory of mice, a discovery which may lead to better treatment for humans.
In the News / Posted April 5, 2007
Scientists find key to memory.
"Memory has been called 'the sublime miracle' of the mind – and a team of Canadian scientists believes it has pinpointed what may be the molecular master switch that underlies our ability for long-term recall.
What's more, they hope their discovery will lead to a drug that can help people with Alzheimer's disease and other forms of dementia, whose ability to remember is increasingly impaired.
The researchers, led by molecular biologist Nahum Sonenberg of McGill University, discovered that laboratory mice with a mutation to a certain gene have an enhanced ability to learn and remember compared to normal mice.
"... 'If such a pill could be generated, it might provide a new method for treating people with memory-related diseases such as Alzheimer's,' said Mauro Costa-Mattioli, a senior postdoctoral fellow in Sonenberg's lab. 'While a drug that worked in this way wouldn't cure the disease itself, it might rescue the symptoms of memory loss.' ..."
Genetic Mutation Boosts Memory
“Working with mice, lead researcher Mauro Costa-Mattioli, a postgraduate fellow at McGill University in Montreal, and colleagues found that rodents that had a defective version of a gene that produces a memory-blocking protein could learn and remember tasks faster than normal mice. ‘We discovered a protein that is called eIF2a that, when mutated, mice have an enhanced memory," Mattioli said. "We hope that this could be a good target to develop a compound that will mimic this mutation, and we can enhance memory in humans,’ he said. ..."
"... for most people, it might take several times to memorize everything. 'But if a human had the same mutation, one would be able to remember it after one reading,' he said. ..."
"...Mattioli thinks that finding a way to get the same memory-enhancing effect in humans could benefit patients with memory loss, including Alzheimer's patients. 'We wouldn't cure Alzheimer's, but, hopefully, we can rescue the memory deficit, which is associated with the disease,' he said.
One expert thinks this discovery could be important in understanding memory loss in Alzheimer's disease. 'Many researchers are pursuing the hypothesis that memory loss in Alzheimer's disease is caused by defects in the complicated machinery controlling the formation of synapses -- the critical connections between nerve cells that define functional circuits,' said Greg M. Cole, associate director of the UCLA Alzheimer's Disease Research Center, and a professor of medicine and neurology at the University of California, Los Angeles. ..."
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