Injection with Toxoplasma gondii protein affects neuron health and survival
- University of Arizona, United States
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
Author details
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.
Reviewing Editor
- Malcolm J McConville, The University of Melbourne, Australia
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).
Version history
- Received: February 18, 2021
- Accepted: June 9, 2021
- Accepted Manuscript published: June 9, 2021 (version 1)
- Version of Record published: July 9, 2021 (version 2)
- Version of Record updated: July 27, 2021 (version 3)
Copyright
© 2021, Mendez et al.
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.
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Injection with Toxoplasma gondii protein affects neuron health and survival
eLife 10:e67681.
https://doi.org/10.7554/eLife.67681
