Format

Send to

Choose Destination
J Neuroinflammation. 2018 Aug 1;15(1):216. doi: 10.1186/s12974-018-1242-1.

Chronic Toxoplasma infection is associated with distinct alterations in the synaptic protein composition.

Author information

1
Institute of Inflammation and Neurodegeneration, Otto von Guericke University Magdeburg, Magdeburg, Germany.
2
Leibniz Institute for Neurobiology, Magdeburg, Germany.
3
Medical Faculty, Department of Neurology, Otto von Guericke University Magdeburg, Magdeburg, Germany.
4
Center for Behavioral Brain Sciences, Magdeburg, Germany.
5
Helmholtz Centre for Infection Research, Cellular Proteomics Group, Braunschweig, Germany.
6
Centro Integrativo de Biología y Química Aplicada, Universidad Bernardo O'Higgins, Santiago, Chile.
7
Department of Computer Science, Ostfalia University of Applied Sciences, Wolfenbuettel, Germany.
8
Molecular Neurobiology, Medical Faculty, Otto von Guericke University Magdeburg, Magdeburg, Germany.
9
Institute of Inflammation and Neurodegeneration, Otto von Guericke University Magdeburg, Magdeburg, Germany. Ildikodunay@gmail.com.
10
Center for Behavioral Brain Sciences, Magdeburg, Germany. Ildikodunay@gmail.com.

Abstract

BACKGROUND:

Chronic infection with the neurotropic parasite Toxoplasma gondii has been implicated in the risk for several neuropsychiatric disorders. The mechanisms, by which the parasite may alter neural function and behavior of the host, are not yet understood completely.

METHODS:

Here, a novel proteomic approach using mass spectrometry was employed to investigate the alterations in synaptic protein composition in a murine model of chronic toxoplasmosis. In a candidate-based strategy, immunoblot analysis and immunohistochemistry were applied to investigate the expression levels of key synaptic proteins in glutamatergic signaling.

RESULTS:

A comparison of the synaptosomal protein composition revealed distinct changes upon infection, with multiple proteins such as EAAT2, Shank3, AMPA receptor, and NMDA receptor subunits being downregulated, whereas inflammation-related proteins showed an upregulation. Treatment with the antiparasitic agent sulfadiazine strongly reduced tachyzoite levels and diminished neuroinflammatory mediators. However, in both conditions, a significant number of latent cysts persisted in the brain. Conversely, infection-related alterations of key synaptic protein levels could be partly reversed by the treatment.

CONCLUSION:

These results provide evidence for profound changes especially in synaptic protein composition in T. gondii-infected mice with a downregulation of pivotal components of glutamatergic neurotransmission. Our results suggest that the detected synaptic alterations are a consequence of the distinct neuroinflammatory milieu caused by the neurotropic parasite.

KEYWORDS:

Chronic Toxoplasma infection; Neuroinflammation; Synaptic proteins; Toxoplasma gondii

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center