The Toxoplasma Blog: Chronic murine toxoplasmosis is defined by subtle changes in the neuronal connectivity

Recent studies correlate chronic Toxoplasma gondii (T. gondii) infection
with behavioral changes in rodents, besides the seropositivity in
humans is reported to be associated with behavioral and neuropsychiatric
diseases. In this study we investigated if the described behavioral
changes in a murine model of chronic toxoplasmosis are associated with
changes in synaptic plasticity and brain neuronal circuitry. In mice
chronically infected with T. gondii, Magnetic Resonance Imaging (MRI)
data analysis displayed the presence of heterogeneous lesions scattered
throughout all brain areas. However, a higher density of lesions could
be observed within specific regions such as the somatosensory cortex
(SSC). Further histopathological examination of these brain areas
indicated the presence of activated resident glia and recruited immune
cells accompanied by limited alterations of neuronal viability. In vivo
Diffusion Tensor MRI analysis of neuronal fiber density within the
infected regions revealed connectivity abnormalities in the SSC. Altered
fiber density was confirmed by morphological analysis of individual,
pyramidal and granule neurons showing a reduction in dendritic arbor and
spine density within the SSC, as well as in the hippocampus. Evaluation
of synapse efficacy revealed diminished levels of two key synaptic
proteins, PSD95 and Synaptophysin, within the same brain areas
indicating deficits in functionality of the synaptic neurotransmission
in infected mice. Our results demonstrate that persistent T. gondii
infection in a murine model results in synaptic deficits within brain
structures leading to disturbances in the morphology of noninfected
neurons and modified brain connectivity, suggesting a potential
explanation for the behavioral and neuropsychiatric alterations.

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