Laing, C, Blanchard, N and McConkey, GA orcid.org/0000-0001-6529-794X (2020) Noradrenergic Signaling and Neuroinflammation Crosstalk Regulate Toxoplasma gondii-Induced Behavioral Changes. Trends in Immunology, 41 (12). pp. 1072-1082. ISSN 1471-4906
Abstract
In the central nervous system (CNS), neuroimmune crosstalk is mediated by neural-cell-derived neurotransmitters and immune cytokines.
CNS infections can induce cognitive alterations with neurotransmitter changes and neuroinflammation. The contribution and interplay of these two pathways are weakly defined. Upon infection, Toxoplasma gondii persists in the CNS, induces behavioral changes, neuroinflammation, and downregulates the neurotransmitter norepinephrine.
Norepinephrine activates noradrenergic signaling in brain glial cells and peripherally recruited immune cells, thereby modulating neuroinflammation.
During chronic T. gondii infection in rodents, we propose that the parasite-induced reduction in norepinephrine results in reduced noradrenergic signaling in CNS immune cells, in turn unleashing proinflammatory mechanisms, which may finally alter cognitive functions.
Infections of the nervous system elicit neuroimmune responses and alter neurotransmission, affecting host neurological functions. Chronic infection with the apicomplexan parasite Toxoplasma correlates with certain neurological disorders in humans and alters behavior in rodents. Here, we propose that the crosstalk between neurotransmission and neuroinflammation may underlie some of these cognitive changes. We discuss how T. gondii infection suppresses noradrenergic signaling and how the restoration of this pathway improves behavioral aberrations, suggesting that altered neurotransmission and neuroimmune responses may act in concert to perturb behavior. This interaction might apply to other infectious agents, such as viruses, that elicit cognitive changes. We hypothesize that neurotransmitter signaling in immune cells can contribute to behavioral changes associated with brain infection, offering opportunities for potential therapeutic targeting.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 Elsevier Ltd. All rights reserved. This is an author produced version of an article published in Trends in Immunology. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 30 Nov 2020 11:27 |
Last Modified: | 16 Nov 2021 01:38 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.it.2020.10.001 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:168408 |