Epigenetic dysregulation of host gene expression in Toxoplasma infection with specific reference to dopamine and amyloid pathways.
Infect Genet Evol
; 65: 159-162, 2018 11.
Article
en En
| MEDLINE
| ID: mdl-30055328
ABSTRACT
Recent interest has focussed on the influence of infectious disease organisms on the host epigenome. Toxoplasma gondii infection acquired congenitally or in early life is associated with severe ocular and brain developmental anomalies, while persistent asymptomatic infection is a proposed risk factor for neurodegenerative and psychiatric disorders, including Parkinson's and Alzheimer's Diseases, and schizophrenia. Genome-wide analysis of the host methylome and transcriptome following T. gondii infection in a retinal cell line identified genes (132, 186 and 128 genes at 2, 6 and 24â¯h post-infection) concordant for methylation and expression, i.e. hypermethylated and decreased expression or hypomethylated and increased expression. Pathway analyses showed perturbation of two neurologically-associated pathways dopamine-DARPP32 feedback in cAMP signalling (p-valueâ¯=â¯8.3â¯×â¯10-5; adjusted p-valueâ¯=â¯0.020); and amyloid processing (p-valueâ¯=â¯1.0â¯×â¯10-3; adjusted p-valueâ¯=â¯0.043). Amyloid Precursor Protein (APP) decreased in level following T. gondii infection. These results are of interest given the expression of APP early in nervous system development affecting neural migration and the role of amyloid processing in Alzheimer's disease, while dopamine has roles in the developing retina as well as in Parkinson's disease and schizophrenia. Our results provide a possible functional link between T. gondii infection and congenital/early life and adult neurological clinical signs.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Dopamina
/
Toxoplasmosis
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Epigénesis Genética
/
Interacciones Huésped-Parásitos
/
Amiloide
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Infect Genet Evol
Asunto de la revista:
BIOLOGIA
/
DOENCAS TRANSMISSIVEIS
/
GENETICA
Año:
2018
Tipo del documento:
Article