title: Chronic infection of Toxoplasma gondii downregulates miR-132 expression in multiple brain regions in a sex-dependent manner.
abstract: MicroRNA-132 (miR-132) has been demonstrated to affect multiple neuronal functions and its dysregulation is linked to several neurological disorders. We previously showed that acute Toxoplasma gondii infection induces miR-132 expression both in vitro and in vivo. To investigate the impact of chronic infection on miR-132, we infected mice with T. gondii PRU strain and performed assessment 5 months later in six brain regions (cortex, hypothalamus, striatum, cerebellum, olfactory bulb and hippocampus) by qPCR. We found that while acute infection of T. gondii increases the expression of miR-132, chronic infection has the opposite effect. The effect varied amongst different regions of the brain and presented in a sex-dependent manner, with females exhibiting more susceptibility than males. MiR-132 and brain-derived neurotrophic factor (BDNF, an inducer of miR-132) were not co-varies in the brain areas of infected mice. T. gondii DNA/RNA was found in all tested brain regions and a selective tropism towards the hippocampus, based on bradyzoite density, was observed in both males and females. However, the expressions of miR-132 or BDNF were poorly reflected by the density of T. gondii in brain areas. Our findings highlight the importance of investigating the miR-132-mediated neuronal function in mice infected with T. gondii.
authors.affiliation: Stanley Division of Developmental Neurovirology,Department of Pediatrics,Johns Hopkins School of Medicine,Baltimore,Maryland 21287,USA.
authors.forename: Y E
authors.initials: YE
authors.lastname: Li
authors.affiliation: Division of Neurobiology,Department of Psychiatry,Johns Hopkins School of Medicine,Baltimore,Maryland 21287,USA.
authors.forename: Geetha
authors.initials: G
authors.lastname: Kannan
authors.affiliation: Division of Neurobiology,Department of Psychiatry,Johns Hopkins School of Medicine,Baltimore,Maryland 21287,USA.
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Pletnikov
authors.affiliation: Stanley Division of Developmental Neurovirology,Department of Pediatrics,Johns Hopkins School of Medicine,Baltimore,Maryland 21287,USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Yolken
authors.affiliation: Stanley Division of Developmental Neurovirology,Department of Pediatrics,Johns Hopkins School of Medicine,Baltimore,Maryland 21287,USA.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000469:parasitology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000469:parasitology; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D059208:Parasite Load; D060888:Real-Time Polymerase Chain Reaction; D048348:Reverse Transcription; D012737:Sex Factors; D014122:Toxoplasma; D014124:Toxoplasmosis, Animal / Q000378:metabolism*; D016781:Toxoplasmosis, Cerebral / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C546976:MIRN132 microRNA, mouse; D035683:MicroRNAs
keywords: host sex