In:
PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 16, No. 7 ( 2022-7-20), p. e0010600-
Abstract:
During chronic infection, the single celled parasite, Toxoplasma gondii , can migrate to the brain where it has been associated with altered dopamine function and the capacity to modulate host behavior, increasing risk of neurocognitive disorders. Here we explore alterations in dopamine-related behavior in a new mouse model based on stimulant (cocaine)-induced hyperactivity. In combination with cocaine, infection resulted in heightened sensorimotor deficits and impairment in prepulse inhibition response, which are commonly disrupted in neuropsychiatric conditions. To identify molecular pathways in the brain affected by chronic T . gondii infection, we investigated patterns of gene expression. As expected, infection was associated with an enrichment of genes associated with general immune response pathways, that otherwise limits statistical power to identify more informative pathways. To overcome this limitation and focus on pathways of neurological relevance, we developed a novel context enrichment approach that relies on a customized ontology. Applying this approach, we identified genes that exhibited unexpected patterns of expression arising from the combination of cocaine exposure and infection. These include sets of genes which exhibited dampened response to cocaine in infected mice, suggesting a possible mechanism for some observed behaviors and a neuroprotective effect that may be advantageous to parasite persistence. This model offers a powerful new approach to dissect the molecular pathways by which T . gondii infection contributes to neurocognitive disorders.
Type of Medium:
Online Resource
ISSN:
1935-2735
DOI:
10.1371/journal.pntd.0010600
DOI:
10.1371/journal.pntd.0010600.g001
DOI:
10.1371/journal.pntd.0010600.g002
DOI:
10.1371/journal.pntd.0010600.g003
DOI:
10.1371/journal.pntd.0010600.g004
DOI:
10.1371/journal.pntd.0010600.g005
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10.1371/journal.pntd.0010600.g006
DOI:
10.1371/journal.pntd.0010600.s001
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10.1371/journal.pntd.0010600.s002
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10.1371/journal.pntd.0010600.s003
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10.1371/journal.pntd.0010600.s004
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10.1371/journal.pntd.0010600.s005
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10.1371/journal.pntd.0010600.s006
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10.1371/journal.pntd.0010600.s007
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10.1371/journal.pntd.0010600.s008
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10.1371/journal.pntd.0010600.s009
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10.1371/journal.pntd.0010600.s010
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10.1371/journal.pntd.0010600.s011
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10.1371/journal.pntd.0010600.s012
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10.1371/journal.pntd.0010600.s013
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10.1371/journal.pntd.0010600.s014
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10.1371/journal.pntd.0010600.s015
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10.1371/journal.pntd.0010600.s016
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10.1371/journal.pntd.0010600.s017
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10.1371/journal.pntd.0010600.s018
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10.1371/journal.pntd.0010600.s019
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10.1371/journal.pntd.0010600.s020
DOI:
10.1371/journal.pntd.0010600.s021
DOI:
10.1371/journal.pntd.0010600.s022
DOI:
10.1371/journal.pntd.0010600.s023
DOI:
10.1371/journal.pntd.0010600.r001
DOI:
10.1371/journal.pntd.0010600.r002
DOI:
10.1371/journal.pntd.0010600.r003
DOI:
10.1371/journal.pntd.0010600.r004
DOI:
10.1371/journal.pntd.0010600.r005
DOI:
10.1371/journal.pntd.0010600.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2429704-5
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