Infection with the common parasite Toxoplasma gondii promotes accumulation of a neurotransmitter in the brain called glutamate, triggering neurodegenerative diseases in individuals predisposed to such conditions.
Written by Honor Whiteman
This is the finding of a new study conducted by researchers from the University of California-Riverside (UC-Riverside), recently published in PLOS Pathogens.
T. gondii is a single-celled parasite that can cause a disease known as toxoplasmosis.
Infection with the parasite most commonly occurs through eating undercooked, contaminated meat or drinking contaminated water.
It may also occur through accidentally swallowing the parasite after coming into contact with cat feces – by cleaning a litter tray, for example.
Though more than 60 million people in the United States are believed to be infected with T. gondii, few people become ill from it; a healthy immune system can normally stave it off.
As such, most people who become infected with the parasite are unaware of it.
Those who do become ill from T. gondii infection may experience flu-like symptoms – such as swollen lymph glands or muscle aches – that last for at least a month.
In severe cases, toxoplasmosis can cause damage to the eyes, brain, and other organs, though such complications usually only arise in people with weakened immune systems.
The new study, however, suggests there may be another dark side to T. gondii infection: it may lead to development of neurodegenerative disease in people who are predisposed to it.
To reach their findings, lead author Emma Wilson – an associate professor in the Division of Biomedical Sciences at the UC-Riverside School of Medicine – and colleagues focused on how T. gondii infection in mice affects glutamate production
How a build-up of glutamate can damage the brain
Glutamate is an amino acid released by nerve cells, or neurons. It is one of the brain’s most abundant excitatory neurotransmitters, aiding communication between neurons.
However, previous studies have shown that too much glutamate may cause harm; a build-up of glutamate is often found in individuals with traumatic brain injury (TBI) and people with certain neurodegenerative diseases, such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS).
The researchers explain that excess glutamate accumulates outside of neurons, and this build-up is regulated by astrocytes – cells in the central nervous system (CNS).
Astrocytes use a glutamate transporter called GLT-1 in an attempt to remove excess glutamate from outside of neurons and convert it into a less harmful substance called glutamine, which cells use for energy.
“When a neuron fires, it releases glutamate into the space between itself and a nearby neuron,” explains Wilson. “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.”
T. gondii increases glutamate by inhibiting GLT-1
n mice infected with T. gondii, the researchers identified an increase in glutamate levels.
They found that the parasite causes astrocytes to swell, which impairs their ability to regulate glutamate accumulation outside of neurons.
Furthermore, the parasite prevents GLT-1 from being properly expressed, which causes an accumulation of glutamate and misfiring of neurons. This may lead to neuronal death, and ultimately, neurodegenerative disease.
“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.” – Emma Wilson
Next, the researchers gave the infected mice an antibiotic called ceftriaxone, which has shown benefits in mouse models of ALS and a variety of CNS injuries.
They found the antibiotic increased expression of GLT-1, which led to a reduction in glutamate build-up and restored neuronal function.
Wilson says their study represents the first time that T. gondii has been shown to directly disrupt a key neurotransmitter in the brain.
“More direct and mechanistic research needs to be performed to understand the realities of this very common pathogen,” she adds.
While their findings indicate a link between T. gondii infection and neurodegenerative disease, Wilson says they should not be cause for panic.
“We have been living with this parasite for a long time,” she says. “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.”
The team now plans to further investigate what causes the reduced expression of GLT-1 in T. gondii infection.
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