Systems analysis points to links between Toxoplasma infection and common brain diseasesSeptember 13, 2017
More than 2 billion people - nearly one out of every three humans on earth, including about 60 million people in the United States - have a lifelong infection with the brain-dwelling parasite Toxoplasma gondii.
In the September 13, 2017, issue of Scientific Reports, 32 researchers from 16 institutions describe efforts to learn how infection with this parasite may alter, and in some cases amplify, several brain disorders, including epilepsy, Alzheimer's and Parkinson's diseases as well as some cancers.
When a woman gets infected with T. gondii during pregnancy and passes the parasite on to her unborn child, the consequences can be profound, including devastating damage to the brain, nervous system and eyes.
There is growing evidence, however, that acquiring this infection later in life may be far from harmless. So the researchers began looking for connections between this chronic but seemingly dormant infection and its potential to alter the course of common neurologic disorders.
"We wanted to understand how this parasite, which lives in the brain, might contribute to and shed light on pathogenesis of other, brain diseases," said Rima McLeod, MD, professor of ophthalmology & visual science and pediatrics and medical director of the Toxoplasmosis Center at the University of Chicago.
"We suspect it involves multiple factors," she said. "At the core is alignment of characteristics of the parasite itself, the genes it expresses in the infected brain, susceptibility genes that could limit the host's ability to prevent infection, and genes that control susceptibility to other diseases present in the human host. Other factors may include pregnancy, stress, additional infections, and a deficient microbiome. We hypothesized that when there is confluence of these factors, disease may occur."
For more than a decade, researchers have noted subtle behavior manipulations associated with a latent T. gondii infection. Rats and mice that harbor this parasite, for example, lose their aversion to the smell of cat urine. This is perilous for a rodent, making it easier for cats to catch and eat them. But it benefits cats, who gain a meal, as well as the parasites, who gain a new host, who will distribute them widely into the environment. An acutely infected cat can excrete up to 500 million oocysts in a few weeks' time. Even one oocyst, which can remain in soil or water for up to a year, is infectious.
A more recent study found a similar connection involving primates. Infected chimpanzees lose their aversion to the scent of urine of their natural predator, leopards.
The research team decided to search for similar effects in people. They focused on what they call the human "infectome" - plausible links between the parasite's secreted proteins, expressed human microRNAs, the neural chemistry of the human host, and the multiple pathways that are perturbed by host-parasite interactions.
Using data collected from the National Collaborative Chicago-Based Congenital Toxoplasmosis Study, which has diagnosed, treated and followed 246 congenitally infected persons and their families since 1981, they performed a "comprehensive systems analysis," looking at a range of parasite-generated biomarkers and assessing their probable impact.
Working with the J Craig Venter Institute and the Institute of Systems Biology Scientists, they looked at the effect of infections of primary neuronal stem cells from the human brain in tissue culture, focusing on gene expression and proteins perturbed. Part of the team, including Huan Ngo from Northwestern University, Hernan Lorenzi at the J Craig Venter Institute, Kai Wang and Taek-Kyun Kim at the Institute for Systems Biology and McLeod, integrated host genetics, proteomics, transcriptomics and circulating microRNA datasets to build a model of these effects on the human brain.
Using what they called a "reconstruction and deconvolution," approach, the researchers identified perturbed pathways associated with neurodegenerative diseases as well as connections between toxoplasmosis, human brain disorders and some cancers.
They also found that:
- Small regulatory biomarkers - bits of microRNA or proteins found in children with severe toxoplasmosis - matched those found in patients with neurodegenerative diseases like Alzheimer's or Parkinson's disease.
- The parasite was able to manipulate 12 human olfactory receptors in ways that mimicked the cat-mouse or the chimp-leopard exchange.
- Evidence that T. gondii could increase the risk of epilepsy, "possibly by altering GABAergic signaling."
- T. gondii infection was associated with a network of 1,178 human genes, many of which are modified in various cancers.
"This study is a paradigm shifter," said co-author Dennis Steinler, PhD, director of the Neuroscience and Aging Lab at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. "We now have to insert infectious disease into the equation of neurodegenerative diseases, epilepsy and neural cancers."
"At the same time," he added, "we have to translate aspects of this study into preventive treatments that include everything from drugs to diet to life style, in order to delay disease onset and progression."
Additional authors include Ying Zhou, Kamal El Bissati, Ernest Mui, Laura Fraczek, Fiona L. Henriquez, Kelsey Wheeler, Ian Begeman, Carlos Naranjo-Galvis, Ney Alliey-Rodriguez and Shawn Withers from the University of Chicago; Huan Ngo, Gwendolyn Noble and Charles N. Swisher from Northwestern University; Hernan Lorenzi and Seesandra V. Rajagopala from the Craig Venter Institute; Kai Wang, Taek-Kyun Kim, Yong Zhou and Leroy Hood from the Institute of Systems Biology, Seattle; Craig W. Roberts from the 6University of Strathclyde, Glasgow; Alexandre Montpetit from Genome Quebec, Montréal, Canada; Jenefer Blackwell from McGill University; Sarra Jamieson from the University of Western Australia; Roderick Davis from the University of Illinois-Chicago, Liliana Soroceanu from California Pacific Medical Center, Charles Cobbs from Tufts University, Kenneth Boyer and Peter Heydemann from Rush University Medical Center, Chicago; Peter Rabiah from Northshore University Health System, Evanston, IL; and Patricia Soteropoulos from Rutgers University.
University of Chicago Medical Center
Related Epilepsy Articles:
There's good news for kids with epilepsy. While several new drugs have come out in the last several years for adults with epilepsy, making those drugs available for children and teenagers has been delayed due to the challenges of testing new drugs on children.
People with epilepsy want their health care providers to tell them about a rare risk of death associated with the disorder, according to a preliminary study released today that will be presented at the American Academy of Neurology's 69th Annual Meeting in Boston, April 22 to 28, 2017.
Scientists have discovered a gene network in the brain associated with epilepsy.
New research from the University of Liverpool, published in the journal Brain, has highlighted the potential reasons why many patients with severe epilepsy still continue to experience seizures even after surgery.
Approximately 2.9 million people in the United States suffer from epilepsy, according to the CDC.
Long-term use of antiepileptic drugs is a significant risk factor for vitamin D deficiency in children with epilepsy.
Researchers at Case Western Reserve University have found that the parasympathetic nervous system modulates breathing and slows the heart rate of sleeping children with epilepsy substantially more than in healthy children.
To increase understanding of mortality in epilepsy, including SUDEP, Partners Against Mortality in Epilepsy (PAME) unites physicians, scientists, health care professionals, people with epilepsy, caregivers and bereaved family members for a unique conference that facilitates collaboration and spurs action.
A study published ahead of print in the Journal of General Physiology has revealed new insights into Retigabine, a known pharmacological treatment for epilepsy.
In the largest study of contraceptive practices of women with epilepsy, 30 percent did not use highly effective contraception despite being at higher risk of having children with fetal malformations due to the anti-epilepsy medications they take.
Related Epilepsy Reading:
Epilepsy Board Review: A Comprehensive Guide
by Mohamad Z. Koubeissi (Editor), Nabil J. Azar (Editor)
This concise text mirrors the content of the Epilepsy Board as distributed by the American Board of Psychiatry and Neurology. Epilepsy diagnosis, classification and treatment are thoroughly covered, along with seizure classification, epidemiology, normal and abnormal EEG, and treatment with antiepileptic medications and other modalities. Formatted with multiple choice questions and explanations, this complete resource will prepare physicians and students for the Epilepsy Board examination and provide the latest clinical approaches.
Navigating Life with Epilepsy (Neurology Now Books)
by David C. Spencer (Author)
Roughly 3 million people in the United States have already been diagnosed with epilepsy and another 200,000 new cases are diagnosed each year. Worldwide, approximately 1 percent of the global population is diagnosed with epilepsy at some point in their lives. With the diagnosis come questions, concerns, and uncertainties from both the person diagnosed and their family. So, where to go?
Navigating Life with Epilepsy provides accessible, comprehensive, and up-to-date information about epilepsy shared from the two decades of experience of epileptologist David Spencer, MD, FAAN. This book... View Details
Mommy, I Feel Funny! A Child's Experience with Epilepsy
by Danielle M. Rocheford (Author), Chris Herrick (Illustrator)
Based on a true story, Mommy, I Feel Funny! introduces the reader to Nel, a little girl who is diagnosed with epilepsy. The story takes you through the days following Nels first seizure. Suddenly, Nel and her family are faced with thoughts, fears and emotions that come with the discovery, understanding and acceptance of epilepsy. View Details
Epilepsy in Children: What Every Parent Needs to Know
by Orrin Devinsky MD (Author), Erin Conway MS RN CPNP (Author), Courtney Schnabel Glick MS RD CDN (Author)
From a leading neurologist, experienced nurse practitioner, and registered dietitian comes the complete guide to managing your child‚Äôs life with epilepsy. Epilepsy in Children offers the practical advice and information you need to respond to your child‚Äôs seizures safely and effectively, understandthe latest treatment options, and find hope for a seizure-free future.Get the right diagnosis for your child and the correct treatment to reduce the frequency of seizures faster Learn the benefits and risks of pharmaceutical, surgical, and alternative... View Details
EPILEPSY 101-The Ultimate Guide for patients and Families
by The National Epilepsy Educational Alliance (Author), Dr. Ruben Kuzniecky (Editor)
This patient and family guide to seizures and epilepsy was written by the leading epilepsy experts in the USA. This effort resulted in a balanced, comprehensive and informative guide intended to inform and guide patient and families through the the diagnosis, treatment and outcome of the disorder. The text is also meant to me used as a companion helping patients with side effects, treatment options, resources, etc. View Details
The Sacred Disease: My Life with Epilepsy
by Kristin Seaborg MD (Author)
Young Kristin Seaborg had the world at her fingertips: a loving family, happiness and security, early admission to medical school--until the frightening diagnosis of epilepsy threatened to destroy both her career path and her health. Living in constant fear that her seizures would intensify and prevent her from practicing medicine, Kristin kept her condition a closely guarded secret, leading a tenuous double life as patient and practitioner. A memoir of discovery, acceptance, and hope, The Sacred Disease chronicles Kristin’s tenacious fight for a seizure-free life. Remarkably, although... View Details
Treating Epilepsy Naturally : A Guide to Alternative and Adjunct Therapies
by Patricia A. Murphy (Author)
Hard-to-find information on epilepsy, presented by an author living successfully with the condition
Drugs commonly used to treat epilepsy have some extremely harmful side effects. Treating Epilepsy Naturally is an empathetic, practical, empowering look at treatment options, lifestyle choices, and ways of living well. Written by an author who has been successfully living with it herself for most of her adult life, this comprehensive guide offers alternative treatments to replace and to complement traditional therapies and sound advice to find the right health... View Details
The Great Katie Kate Explains Epilepsy
by M. Maitland DeLand (Author), Jennifer Zivoin (Illustrator)
A book designed specifically to help young epilepsy patients understand their condition and overcome their fears
When Jimmy is diagnosed with epilepsy, he starts to worry. What is happening to my body? Am I ok? Does this mean I m different from other kids?
Jimmy and the other young patients in the neurologist's office get a visit from the Great Katie Kate, a spunky redheaded superhero who appears when kids get worried. Katie Kate takes the children on a medical adventure to learn about the various forms of epileptic seizures and treatments. Along the way, they meet the Worry... View Details
Epilepsy Board Review
by Pradeep N. Modur MD MS (Author), Puneet K. Gupta MD MSE (Author), Deepa Sirsi MD (Author)
Epilepsy Board Review is designed as a primary study tool to help candidates prepare for the epilepsy board certification exam. Using structured question formats typically encountered on the boards, this book covers the base knowledge tested and allows users to assess their proficiency in a wide range of topics necessary to achieve subspecialty certification in the field of epilepsy.
This high-yield review contains over 360 questions with answers, detailed explanations, and references. The book consists of four parts that cover the phenomenology of seizures and epileptic disorders,... View Details
Seizures and Epilepsy in Childhood: A Guide (Johns Hopkins Press Health Book)
by John M. Freeman MD (Author), Eileen P. G. Vining MD (Author), Diana J. Pillas (Author)
The award-winning Seizures and Epilepsy in Childhood is the standard resource for parents in need of comprehensive medical information about their child with epilepsy. Now in its third edition, this highly praised book has been thoroughly revised and updated to reflect the latest approaches to the diagnosis and treatment of epilepsy in childhood, including the use of the ketogenic diet as a treatment for children who either do not respond to traditional drug therapy or who suffer intolerable side effects from medications.
In addition to providing up-to-date information about... View Details