MicroRNA-132 dysregulation in Toxoplasma gondii infection has implications for dopamine signaling pathway

Research output: Contribution to journalArticle

Abstract

Congenital toxoplasmosis and toxoplasmic encephalitis can be associated with severe neuropsychiatric symptoms. However, which host cell processes are regulated and how Toxoplasma gondii affects these changes remain unclear. MicroRNAs (miRNAs) are small noncoding RNA sequences critical to neurodevelopment and adult neuronal processes by coordinating the activity of multiple genes within biological networks. We examined the expression of over 1000 miRNAs in human neuroepithelioma cells in response to infection with Toxoplasma. MiR-132, a cyclic AMP-responsive element binding (CREB)-regulated miRNA, was the only miRNA that was substantially upregulated by all three prototype Toxoplasma strains. The increased expression of miR-132 was also documented in mice following infection with Toxoplasma. To identify cellular pathways regulated by miR-132, we performed target prediction followed by pathway enrichment analysis in the transcriptome of Toxoplasma-infected mice. This led us to identify 20 genes and dopamine receptor signaling was their strongest associated pathway. We then examined myriad aspects of the dopamine pathway in the striatum of Toxoplasma -infected mice 5. days after infection. Here we report decreased expression of D1-like dopamine receptors (DRD1, DRD5), metabolizing enzyme (MAOA) and intracellular proteins associated with the transduction of dopamine-mediated signaling (DARPP-32 phosphorylation at Thr34 and Ser97). Increased concentrations of dopamine and its metabolites, serotonin (5-HT) and 5-hydroxyindoleacetic acid were documented by HPLC analysis; however, the metabolism of dopamine was decreased and 5-HT metabolism was unchanged. Our data show that miR-132 is upregulated following infection with Toxoplasma and is associated with changes in dopamine receptor signaling. Our findings provide a possible mechanism for how the parasite contributes to the neuropathology of infection.

Original languageEnglish (US)
Pages (from-to)128-138
Number of pages11
JournalNeuroscience
Volume268
DOIs
StatePublished - May 30 2014

Fingerprint

Toxoplasmosis
Toxoplasma
MicroRNAs
Dopamine
Infection
Serotonin
Dopamine Receptors
Congenital Toxoplasmosis
Small Untranslated RNA
Dopamine D1 Receptors
Hydroxyindoleacetic Acid
Gene Expression Profiling
Encephalitis
Cyclic AMP
Genes
Parasites
High Pressure Liquid Chromatography
Phosphorylation
Enzymes
Proteins

Keywords

  • Alteration in expression
  • Dopamine receptor pathway
  • MiR-132
  • Mouse striatum
  • Toxoplasma gondii

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

@article{e57242f243474e9f8728f24b98e6ae2a,
title = "MicroRNA-132 dysregulation in Toxoplasma gondii infection has implications for dopamine signaling pathway",
abstract = "Congenital toxoplasmosis and toxoplasmic encephalitis can be associated with severe neuropsychiatric symptoms. However, which host cell processes are regulated and how Toxoplasma gondii affects these changes remain unclear. MicroRNAs (miRNAs) are small noncoding RNA sequences critical to neurodevelopment and adult neuronal processes by coordinating the activity of multiple genes within biological networks. We examined the expression of over 1000 miRNAs in human neuroepithelioma cells in response to infection with Toxoplasma. MiR-132, a cyclic AMP-responsive element binding (CREB)-regulated miRNA, was the only miRNA that was substantially upregulated by all three prototype Toxoplasma strains. The increased expression of miR-132 was also documented in mice following infection with Toxoplasma. To identify cellular pathways regulated by miR-132, we performed target prediction followed by pathway enrichment analysis in the transcriptome of Toxoplasma-infected mice. This led us to identify 20 genes and dopamine receptor signaling was their strongest associated pathway. We then examined myriad aspects of the dopamine pathway in the striatum of Toxoplasma -infected mice 5. days after infection. Here we report decreased expression of D1-like dopamine receptors (DRD1, DRD5), metabolizing enzyme (MAOA) and intracellular proteins associated with the transduction of dopamine-mediated signaling (DARPP-32 phosphorylation at Thr34 and Ser97). Increased concentrations of dopamine and its metabolites, serotonin (5-HT) and 5-hydroxyindoleacetic acid were documented by HPLC analysis; however, the metabolism of dopamine was decreased and 5-HT metabolism was unchanged. Our data show that miR-132 is upregulated following infection with Toxoplasma and is associated with changes in dopamine receptor signaling. Our findings provide a possible mechanism for how the parasite contributes to the neuropathology of infection.",
keywords = "Alteration in expression, Dopamine receptor pathway, MiR-132, Mouse striatum, Toxoplasma gondii",
author = "Jian-Chun Xiao and Y. Li and E. Prandovszky and Senthilkumar Karuppagounder and Talbot, {C. C.} and Valina Dawson and Dawson, {Ted M} and Yolken, {Robert H}",
year = "2014",
month = "5",
day = "30",
doi = "10.1016/j.neuroscience.2014.03.015",
language = "English (US)",
volume = "268",
pages = "128--138",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - MicroRNA-132 dysregulation in Toxoplasma gondii infection has implications for dopamine signaling pathway

AU - Xiao, Jian-Chun

AU - Li, Y.

AU - Prandovszky, E.

AU - Karuppagounder, Senthilkumar

AU - Talbot, C. C.

AU - Dawson, Valina

AU - Dawson, Ted M

AU - Yolken, Robert H

PY - 2014/5/30

Y1 - 2014/5/30

N2 - Congenital toxoplasmosis and toxoplasmic encephalitis can be associated with severe neuropsychiatric symptoms. However, which host cell processes are regulated and how Toxoplasma gondii affects these changes remain unclear. MicroRNAs (miRNAs) are small noncoding RNA sequences critical to neurodevelopment and adult neuronal processes by coordinating the activity of multiple genes within biological networks. We examined the expression of over 1000 miRNAs in human neuroepithelioma cells in response to infection with Toxoplasma. MiR-132, a cyclic AMP-responsive element binding (CREB)-regulated miRNA, was the only miRNA that was substantially upregulated by all three prototype Toxoplasma strains. The increased expression of miR-132 was also documented in mice following infection with Toxoplasma. To identify cellular pathways regulated by miR-132, we performed target prediction followed by pathway enrichment analysis in the transcriptome of Toxoplasma-infected mice. This led us to identify 20 genes and dopamine receptor signaling was their strongest associated pathway. We then examined myriad aspects of the dopamine pathway in the striatum of Toxoplasma -infected mice 5. days after infection. Here we report decreased expression of D1-like dopamine receptors (DRD1, DRD5), metabolizing enzyme (MAOA) and intracellular proteins associated with the transduction of dopamine-mediated signaling (DARPP-32 phosphorylation at Thr34 and Ser97). Increased concentrations of dopamine and its metabolites, serotonin (5-HT) and 5-hydroxyindoleacetic acid were documented by HPLC analysis; however, the metabolism of dopamine was decreased and 5-HT metabolism was unchanged. Our data show that miR-132 is upregulated following infection with Toxoplasma and is associated with changes in dopamine receptor signaling. Our findings provide a possible mechanism for how the parasite contributes to the neuropathology of infection.

AB - Congenital toxoplasmosis and toxoplasmic encephalitis can be associated with severe neuropsychiatric symptoms. However, which host cell processes are regulated and how Toxoplasma gondii affects these changes remain unclear. MicroRNAs (miRNAs) are small noncoding RNA sequences critical to neurodevelopment and adult neuronal processes by coordinating the activity of multiple genes within biological networks. We examined the expression of over 1000 miRNAs in human neuroepithelioma cells in response to infection with Toxoplasma. MiR-132, a cyclic AMP-responsive element binding (CREB)-regulated miRNA, was the only miRNA that was substantially upregulated by all three prototype Toxoplasma strains. The increased expression of miR-132 was also documented in mice following infection with Toxoplasma. To identify cellular pathways regulated by miR-132, we performed target prediction followed by pathway enrichment analysis in the transcriptome of Toxoplasma-infected mice. This led us to identify 20 genes and dopamine receptor signaling was their strongest associated pathway. We then examined myriad aspects of the dopamine pathway in the striatum of Toxoplasma -infected mice 5. days after infection. Here we report decreased expression of D1-like dopamine receptors (DRD1, DRD5), metabolizing enzyme (MAOA) and intracellular proteins associated with the transduction of dopamine-mediated signaling (DARPP-32 phosphorylation at Thr34 and Ser97). Increased concentrations of dopamine and its metabolites, serotonin (5-HT) and 5-hydroxyindoleacetic acid were documented by HPLC analysis; however, the metabolism of dopamine was decreased and 5-HT metabolism was unchanged. Our data show that miR-132 is upregulated following infection with Toxoplasma and is associated with changes in dopamine receptor signaling. Our findings provide a possible mechanism for how the parasite contributes to the neuropathology of infection.

KW - Alteration in expression

KW - Dopamine receptor pathway

KW - MiR-132

KW - Mouse striatum

KW - Toxoplasma gondii

UR - http://www.scopus.com/inward/record.url?scp=84897529575&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897529575&partnerID=8YFLogxK

U2 - 10.1016/j.neuroscience.2014.03.015

DO - 10.1016/j.neuroscience.2014.03.015

M3 - Article

C2 - 24657774

AN - SCOPUS:84897529575

VL - 268

SP - 128

EP - 138

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

ER -