Summary: Toxoplasma gondii, A protozoan parasite, infects almost a third of the world’s population. Workings on mice biomedical scientists reveal that Toxoplasma infection leads to a disruption of neurotransmitters in the brain and postulates that it triggers neurological disease in those already who are predisposed to such infection. Infection leads to a significant increase in Glutamate- the primary and most important neurotransmitter in the brain.
Toxoplasma gondii:
A protozoan parasite about 5 microns in length, infects a 3rd of the world’s population. It is ingested via undercooked meat or unwashed vegetables. The parasite infects 15-30% of the US population. In France and Brazil, up to 80% of the population has the infection.
This pathogen is particularly dangerous during pregnancy. Infection in pregnant women can cause serious congenital defects and even death of the fetus. The chronic infection has 2 components:
- Unicellular parasite.
- Inflammation of tissues
By working on mice, biomedical scientists have reported 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 predisposed to the infection.
Parasite and neurotransmitter:
Toxoplasma infection leads to a significant rise in glutamate- The primary and most vital neurotransmitter in the brain, that transmits excitatory signals between neurons. This Glutamate increase is “extracellular” meaning concentrations increase outside the cell and is strictly controlled by specialized cells in the CNS called Astrocytes. Glutamate buildup is seen in TBI as well as in neurodegenerating conditions such as Epilepsy, multiple sclerosis and amyotrophic lateral sclerosis (ALS).
Astrocytes help to remove extracellular glutamate, which otherwise leads to neuronal damage. This is achieved by using Glutamate transporter GLT-1, tasked with regulating extracellular glutamate. GLT-1 soaks up glutamate released by neurons and converts it back into safer Glutamine, that can be used by cells for energy.
Glutamate is released when a neuron fires into the space between itself and a nearby neuron. The nearby neuron detects this glutamate which triggers a firing of the neuron. If the glutamate is not cleared by GLT-1 then neurons can’t fire properly the next time and they begin to die.
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. 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.”