Thumbnail Image
Publication

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

Lang, Daniel
; 
Schott, Björn H
; 
van Ham, Marco
; 
Morton, Lorena
; 
Kulikovskaja, Leonora
; 
Herrera-Molina, Rodrigo
; 
Pielot, Rainer
; ; 
Montag, Dirk
; ... show 3 more
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2018-08-01
Submitted date
Show all metadata
Files
Thumbnail Image
Open Access publication
Adobe PDF, 1.9 MB
Other Titles
Abstract
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. 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. 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. 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.
Citation
Affiliation
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Publisher
Journal
URI
http://hdl.handle.net/10033/621498
DOI
10.1186/s12974-018-1242-1
PubMed ID
30068357
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
1742-2094
EISSN
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution-NonCommercial-ShareAlike 3.0 United States
cbn
Collections
publications of the research group cellular proteom research (CPRO)