Alsaady, I, Tedford, E, Alsaad, M et al. (8 more authors) (2019) Downregulation of the central noradrenergic system by Toxoplasma gondii infection. Infection and Immunity, 87 (2). e00789-18. ISSN 0019-9567
Abstract
Toxoplasma gondii is associated with physiological effects in the host. Dysregulation of catecholamines in the central nervous system has previously been observed in chronically-infected animals. In the study described here, the noradrenergic system was found to be suppressed with decreased levels of norepinephrine (NE) in brains of infected animals and in infected human and rat neural cells in vitro. The mechanism responsible for the NE suppression was found to be down-regulation of dopamine β-hydroxylase (DBH) gene expression, encoding the enzyme that synthesizes norepinephrine from dopamine with down-regulation observed in vitro and in infected brain tissue, particularly in the dorsal locus coeruleus/pons region. The down-regulation was sex-specific with males expressing reduced DBH mRNA levels whereas females were unchanged. Rather, DBH expression correlated with estrogen receptor in the female rat brains for this estrogen-regulated gene. DBH silencing was not a general response of neurons to infection as human cytomegalovirus (CMV) did not down-regulate DBH expression. The noradrenergic-linked behaviors of sociability and arousal were altered in chronically-infected animals, with a high correlation between DBH expression and infection intensity. A decrease in DBH expression in noradrenergic neurons can elevate dopamine levels which provides a possible explanation for mixed observations of changes in this neurotransmitter with infection. Decreased NE is consistent with the loss of coordination and motor impairments associated with toxoplasmosis. Further, the altered norepinephrine synthesis observed here may, in part, explain behavioural effects of infection and associations with mental illness.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Copyright © 2018 American Society for Microbiology. This is an author produced version of a paper published in Infection and Immunity, Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Fungal and Parasitic Infections |
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) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 Nov 2018 10:05 |
Last Modified: | 03 Jun 2019 00:43 |
Status: | Published |
Publisher: | American Society for Microbiology |
Identification Number: | 10.1128/IAI.00789-18 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:139131 |