Injection with Toxoplasma gondii protein affects neuron health and survival

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Abstract

Toxoplasma gondii is an intracellular parasite that causes a long-term latent infection of neurons. Using a custom MATLAB-based mapping program in combination with a mouse model that allows us to permanently mark neurons injected with parasite proteins, we found that Toxoplasma-injected neurons (TINs) are heterogeneously distributed in the brain, primarily localizing to the cortex followed by the striatum. In addition, we determined that cortical TINs are commonly (>50%) excitatory neurons (FoxP2⁺) and that striatal TINs are often (>65%) medium spiny neurons (MSNs) (FoxP2⁺). By performing single neuron patch-clamping on striatal TINs and neighboring uninfected MSNs, we discovered that TINs have highly aberrant electrophysiology. As approximately 90% of TINs will die by 8 weeks post-infection, this abnormal physiology suggests that injection with Toxoplasma protein— either directly or indirectly— affects neuronal health and survival. Collectively, these data offer the first insights into which neurons interact with Toxoplasma and how these interactions alter neuron physiology in vivo.

Data availability

Data for Figures 1,2,3,5,6,7 is provided.

Article and author information

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Oscar A Mendez

Neuroscience GIDP, University of Arizona, Tucson, United States

Competing interests
The authors declare that no competing interests exist.
Emiliano Flores Machado

Neuroscience GIDP, University of Arizona, Tucson, United States

Competing interests
The authors declare that no competing interests exist.
Jing Lu

College of Nursing, University of Arizona, Tucson, United States

Competing interests
The authors declare that no competing interests exist.
Anita Koshy

Neurology; Immunobiology, University of Arizona, Tucson, United States

For correspondence
akoshy@arizona.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8705-3233

Funding

National Institute of Neurological Disorders and Stroke (F99 NS108514)

Oscar A Mendez

National Institute of Neurological Disorders and Stroke (R25 NS076437 High School Student NeuroResearch Program (HSNRP))

Emiliano Flores Machado

Arizona Biomedical Research Commission (ADHS14-082991)

Anita Koshy

National Institute of Neurological Disorders and Stroke (R01 NS095994)

Anita Koshy

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All mouse studies and breeding were carried out in accordance with the Public Health Service Policy on Human Care and Use of Laboratory Animals. The protocol was approved by the University of Arizona Institutional Animal Care and Use Committee. (#A-3248-01, protocol #12-391).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.