Schematic of Toxoplasma gondii effects on glutamate and glutamate decarboxylase.
(A) Under normal conditions, glutamate, an excitatory neurotransmitter, is released into the synaptic cleft from the presynaptic neuron. Glutamate then diffuses across the synaptic cleft to act on glutamate receptors on the postsynaptic neuron, leading to excitation of the postsynaptic neuron. This glutamatergic signaling is terminated by uptake and recycling of synaptic glutamate by the glutamate transporter GLT-1 on surrounding astrocytes. Glutamate uptake by GLT-1 is essential to avoid excessive glutamate signaling, which can lead to postsynaptic excitotoxicity and neuronal death. After an infection, GLT-1–dependent transport into astrocytes is impaired, allowing for an increase in glutamate accumulation in the synaptic cleft, which is expected to lead to more excitation of the postsynaptic neuron. (B) Glutamate decarboxylase (GAD) is primarily found on presynaptic terminals, where it will process glutamate into γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain. Once GABA is released into the synaptic cleft, it will bind onto GABA receptors on the postsynaptic neuron, which decreases the excitability of the postsynaptic neuron. In the case of infection, GAD is redistributed into the cytosol of the presynaptic neuron, which would be expected to cause improper GABA localization at synapses, leading to decreased inhibition of the postsynaptic neuron.
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