Uncooked meat and brain disorders

undercooked meat to brain disease

Toxoplasma gondii, a protozoan parasite about five microns long, infects a third of the world’s population. Ingested via undercooked meat or unwashed vegetables, the parasite infects 15-30 percent of the US population. In France and Brazil, up to 80 percent of the population has the infection.

Particularly dangerous during pregnancy – infection in pregnant women can cause serious congenital defects and even death of the fetus – this chronic infection has two components: the unicellular parasite, and inflammation of tissues it causes.

Working on mice (like all mammals, a natural host for this parasite), a University of California, Riverside team of biomedical scientists reports in the journal PLOS Pathogens that Toxoplasma infection leads to a disruption of neurotransmitters in the brain and postulates that it triggers neurological disease in those already predisposed to such a disease.

They note that Toxoplasma infection leads to a significant increase in glutamate – the primary and most important neurotransmitter in the brain, which transmits excitatory signals between neurons. This glutamate increase is “extracellular,” meaning outside the cell, and is strictly controlled by specialized cells in the central nervous system (brain and spinal cord), called astrocytes. Glutamate buildup is seen in traumatic brain injury as well as highly pathological and neurodegenerating diseases such as epilepsy, multiple sclerosis and amyotrophic lateral sclerosis (ALS).

One role astrocytes play is to remove extracellular glutamate, lest it increase to pathological levels that could damage neurons. This is primarily achieved using a glutamate transporter, called GLT-1, tasked with regulating extracellular glutamate. GLT-1 soaks up glutamate released by neurons and converts it back into the safer substance glutamine, which can then be used by cells for energy.

“When a neuron fires it releases glutamate into the space between itself and a nearby neuron,” explained lead researcher Emma H. Wilson, an associate professor in the Division of Biomedical Sciences in the School of Medicine, who has worked on toxoplasmosis for more than 15 years. “The nearby neuron detects this glutamate which triggers a firing of the neuron. If the glutamate isn’t cleared by GLT-1 then the neurons can’t fire properly the next time and they start to die.”

Wilson and her team found that during toxoplasma infection, astrocytes swell and are not able to regulate extracellular glutamate concentrations. Further, GLT-1 is not expressed properly. This leads to a buildup of the glutamate released from neurons and the neurons misfire.

“These results suggest that in contrast to assuming chronic Toxoplasma infection as quiescent and benign, we should be aware of the potential risk to normal neurological pathways and changes in brain chemistry,” Wilson said.

When the researchers treated the infected mice with ceftriaxone, an antibiotic known to produce beneficial results in mouse models of ALS as well as neuroprotection in a variety of central nervous system injuries, they found that GLT-1 was upregulated. This restoration of GLT-1 expression significantly reduced extracellular glutamate from pathological to normal concentrations, returning neuronal function to a normal state.

“We have shown for the first time the direct disruption of a major neurotransmitter in the brain resulting from this infection,” Wilson said. “More direct and mechanistic research needs to be performed to understand the realities of this very common pathogen.”

Next, Wilson and her colleagues will research what initiates the downregulation of GLT-1 during chronic Toxoplasma infection.

“Despite the importance of this transporter to maintaining glutamate homeostasis, there is little understanding of the mechanism that governs its expression,” Wilson said. “We’d like to know how cells, including peripheral immune cells, control the parasite in the brain. Toxoplasma infection results in the lifelong presence of parasitic cysts within the neurons in the brain. We’d like to further develop a project focused on killing the cysts, which is where the parasite hides from the immune response for the rest of the infected person’s life. Getting rid of the cyst removes the threat of reactivation of the parasite and the risk of encephalitis while also allowing us to minimize chronic inflammation in the brain.”

Mysteriously, the parasite that causes toxoplasmosis can sexually reproduce only in cats. Asexually, it can replicate and live in any mammalian cell that has a nucleus. Indeed, the parasite has been found in every mammal ever tested.

Post-infection, a competent immune system is needed to prevent parasite reactivation and encephalitis. Infected people with compromised immune systems need to be on prophylactic drugs for life. Otherwise they are at risk of cyst reactivation and death. The parasite lives in areas of the brain that have the potential to disrupt certain behaviors such as risk-seeking (infected mice will run toward cat urine instead of away from it).

The parasite is not as latent or dormant as researchers once thought. Cases of congenital infection and retinal toxoplasmosis are on the rise (the brain and retina are closely linked). People who have schizophrenia are more likely to be infected with Toxoplasma. Infection shows some correlation with Alzheimer’s disease, Parkinson’s disease and epilepsy.

Nevertheless, Wilson notes that infection is no cause for major worry.

 

“We have been living with this parasite for a long time,” she said. “It does not want to kill its host and lose its home. The best way to prevent infection is to cook your meat and wash your hands and vegetables. And if you are pregnant, don’t change the cat litter.”

Explore further: New research investigates how the common ‘cat parasite’ gets into the brain


Infection in domestic cats

A number of studies have been presented in recent years showing that the toxoplasmosis parasite affects its host even during the dormant phase. It has, for example, already been observed that rats become unafraid of cats and even attracted by their scent, which makes them easy prey. This has been interpreted as the parasite assuring its survival and propagation, since the consumed rat then infects the cat, which through its faces can infect the food that other rats might then proceed to eat. A number of studies also confirm that mental diseases like schizophrenia, depression and anxiety syndrome are more common in people with toxoplasmosis, while others suggest that toxoplasmosis can influence how extroverted, aggressive or risk-inclined an individual’s behaviour is.

 


 

 

More information: PLOS Pathogens, dx.plos.org/10.1371/journal.pat.1005643

 

Journal reference: PLoS Pathogens search and more info website

 

Provided by: University of California – Riverside

A journal retracted a study linking genetically modified corn to tumor growth and death risk in rats

tumors in rats

A scientific journal has formally retracted a controversial study linking genetically modified corn to tumor growth and death risk in rats.

The study had appeared in the Sept. 19, 2012 issue of Food and Chemical Toxicology, and made headlines around the world with its stark images of rats who purportedly were more likely to develop large tumors and die early after eating Monsanto’s genetically modified maize, whether or not it was treated with a weed killer.

But now the journal’s publisher, Elsevier, says the study led by biologist Dr. Gilles-Eric Seralini of Caen University in France is being retracted due to concerns with the research methodology.

Elsevier emphasized there’s no evidence of fraud or intentional misrepresentation.

“This retraction comes after a thorough and time-consuming analysis of the published article and the data it reports, along with an investigation into the peer-review behind the article,” Elsevier said in the statement. “Ultimately, the results presented (while not incorrect) are inconclusive, and therefore do not reach the threshold of publication for Food and Chemical Toxicology.”

For the original study, about 200 albino Sprague-Dawley rats were divided into groups of 10 and fed diets with GM corn cultivated with our without the Roundup weed killer, or they were assigned to drink Roundup alone in water. Twenty rats served as controls.

Female mice on GM diets were found to be two to three times more likely to die than those in the control group, and their health seemed to be more negatively affected by the diets whether it was sprayed with Roundup or not. About 50 percent of males and 70 percent of the females eating Monsanto GM corn died prematurely, compared to 30 percent of males and 20 percent of females not eating the corn.

Large mammary tumors developed in female rats about four months into the two-year study, some that were so large they blocked organ function.

Yet, some experts at the time questioned the findings, nothing Sprague-Dawley rats are more likely to develop tumors anyway, and that 20 rats make for too small of a comparison control group.

“The most evocative part of the paper is those pictures of tumorigenesis,” said Maurice Moloney, a research biologist at Rothamsted Research in Harpenden, England, said in Sept. 2012. “If there was a control that ended up showing similar kinds of tumorigenesis then a picture of that rat should be shown as well, just so we can see if there are any qualitative differences between them.”

The journal’s editor-in-chief began to review these questions and allegations soon after the study was published, and requested to see all the raw data from the researcher, with Seralini complying.

A “more in-depth analysis” showed that “no definitive conclusions can be reached with this small sample size… in regards to overall mortality or tumor incidence.”

Given these rats are more likely to develop tumors, normal variability cannot be excluded as a cause of what the researchers found, according to the journal.

“The peer review process is not perfect, but it does work,” said Elsevier. “The retraction is only on the inconclusiveness of this one paper. The journal’s editorial policy will continue to review all manuscripts no matter how controversial they may be.”

Nature reports the news shouldn’t come as a surprise, because editor-in-chief Wallace Hayes announced earlier this month that he’d retract the paper if Seralini and his colleagues didn’t withdraw the study, which the team reportedly refused to do at a Nov. 28 press conference, standing by their research.

Seralini told Reuters the criticism of his work was “unacceptable” and threatened legal action.

Joel Spiroux, president of the France-based Committee for Research and Independent Information on Genetic Engineering (CRIIGEN), which collaborated on the study, called the retraction a “a public-health scandal” to Nature.

Monsanto could not be reached for comment at press time.

Concerns about health risks of GM foods have led to calls for labeling requirements, which were rejected by voters this year in Washington state and last year in California.

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