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Alterations in Retrotransposition, Synaptic Connectivity, and Myelination Implicated by Transcriptomic Changes Following Maternal Immune Activation in Nonhuman Primates

ABSTRACT: Alterations in Retrotransposition, Synaptic Connectivity, and Myelination Implicated by Transcriptomic Changes Following Maternal Immune Activation in Nonhuman Primates

PROVIDER: PRJNA811148 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18171600_1.fastq.gz	Fastqsanger.gz
	SRR18171600_2.fastq.gz	Fastqsanger.gz
	SRR18171601_1.fastq.gz	Fastqsanger.gz
	SRR18171601_2.fastq.gz	Fastqsanger.gz
	SRR18171602_1.fastq.gz	Fastqsanger.gz

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Alterations in Retrotransposition, Synaptic Connectivity, and Myelination Implicated by Transcriptomic Changes Following Maternal Immune Activation in Nonhuman Primates

Project description:BACKGROUND: Maternal immune activation (MIA) is a proposed risk factor for multiple neuropsychiatric disorders, including schizophrenia. However, the molecular mechanisms through which MIA imparts risk remain poorly un- derstood. A recently developed nonhuman primate model of exposure to the viral mimic poly:ICLC during pregnancy shows abnormal social and repetitive behaviors and elevated striatal dopamine, a molecular hallmark of human psychosis, providing an unprecedented opportunity for studying underlying molecular correlates. METHODS: We performed RNA sequencing across psychiatrically relevant brain regions (prefrontal cortex, anterior cingulate, hippocampus) and primary visual cortex for comparison from 3.5- to 4-year-old male MIA-exposed and control offspring—an age comparable to mid adolescence in humans. RESULTS: We identify 266 unique genes differentially expressed in at least one brain region, with the greatest number observed in hippocampus. Co-expression networks identified region-specific alterations in synaptic signaling and oligodendrocytes. Although we observed temporal and regional differences, transcriptomic changes were shared across first- and second-trimester exposures, including for the top differentially expressed genes—PIWIL2 and MGARP. In addition to PIWIL2, several other regulators of retrotransposition and endogenous transposable elements were dysregulated following MIA, potentially connecting MIA to retrotransposition. CONCLUSIONS: Together, these results begin to elucidate the brain-level molecular processes through which MIA may impart risk for psychiatric disease

2022-03-04 | GSE197605 | GEO

Alterations in Retrotransposition, Synaptic Connectivity, and Myelination Implicated by Transcriptomic Changes Following Maternal Immune Activation in Nonhuman Primates.

Project description:BackgroundMaternal immune activation (MIA) is a proposed risk factor for multiple neuropsychiatric disorders, including schizophrenia. However, the molecular mechanisms through which MIA imparts risk remain poorly understood. A recently developed nonhuman primate model of exposure to the viral mimic poly:ICLC during pregnancy shows abnormal social and repetitive behaviors and elevated striatal dopamine, a molecular hallmark of human psychosis, providing an unprecedented opportunity for studying underlying molecular correlates.MethodsWe performed RNA sequencing across psychiatrically relevant brain regions (prefrontal cortex, anterior cingulate, hippocampus) and primary visual cortex for comparison from 3.5- to 4-year-old male MIA-exposed and control offspring-an age comparable to mid adolescence in humans.ResultsWe identify 266 unique genes differentially expressed in at least one brain region, with the greatest number observed in hippocampus. Co-expression networks identified region-specific alterations in synaptic signaling and oligodendrocytes. Although we observed temporal and regional differences, transcriptomic changes were shared across first- and second-trimester exposures, including for the top differentially expressed genes-PIWIL2 and MGARP. In addition to PIWIL2, several other regulators of retrotransposition and endogenous transposable elements were dysregulated following MIA, potentially connecting MIA to retrotransposition.ConclusionsTogether, these results begin to elucidate the brain-level molecular processes through which MIA may impart risk for psychiatric disease.

| S-EPMC8052273 | biostudies-literature

Spatial transcriptomics on Zika virus infected fetal brains of nonhuman primates

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Intra-amniotic Balloon Inflation Induces an Inflammatory “Pulse” and Labor in Nonhuman Primates

Project description:Uterine stretch is thought to induce preterm labor in women with twin and higher order pregnancies, but the pathophysiology remains unclear. We investigated the pathogenesis of stretch-induced preterm birth for the first time in a pregnant nonhuman primate model. Eleven chronically catheterized pregnant monkeys (Macaca nemestrina) at 118-125 days gestation (term=172 days) received either: 1) inflation of intra-amniotic balloons (N=6) or 2) saline inoculation (N=5). Cesarean section and fetal necropsy was performed due to preterm labor or to collect tissues, except in one case where the animal delivered spontaneously, reducing samples for microarray analysis to ten (five stretch and five control animals). Amniotic fluid and maternal plasma were analyzed for multiple cytokines and prostaglandins using Luminex, enzyme-linked immunosorbent assay and Analysis of Covariance. Ribonucleic acid was extracted from the myometrium in the lower uterus at Cesarean section and analyzed by microarray and quantitative reverse transcriptase polymerase chain reaction.

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Transcriptomic diversity of amygdalar subdivisions across humans and nonhuman primates

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