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Kiernan, E.

Publications and source records attributed to Kiernan, E..

4 recordsLinked to original sources

Impact of Cesarean Delivery on Reward Behavior and Neurodevelopment in Adult Prairie Vole Offspring

Accumulating clinical evidence has shown that birth by Cesarean section (CS) is associated with a higher incidence of disorders involving the dysregulation of dopamine (DA), such as attention deficit-hyperactivity disorder, autism spectrum disorder, and obesity, compared to vaginal delivery (VD). The mesolimbic (ML) system encompasses DAergic neurons that modulate reward processes underlying learning, motivation, and food intake. Previous research has shown that there are lower levels of DA in the prefrontal cortex and higher in the nucleus accumbens (NAc) of CS offspring. Alterations in the ML-DA system as a consequence of birth via CS may impact behavioral response to rewarding stimuli, such as food. Thus, we aimed to ascertain the behavioral and neurodevelopmental outcomes relevant to food reward in CS prairie vole offspring. This study utilized conditioned place preference (CPP) testing to assess learning using context-dependent conditioning, operant conditioning to assess acquisition of a conditioned response and motivation to receive a reinforcer, and immunohistochemistry (IHC) to stain for tyrosine hydroxylase (TH) in the NAc. Behavioral results showed no difference in preference for the conditioned chamber during CPP testing between CS offspring and their VD counterparts. CS prairie vole offspring had a lower average break point during progressive-ratio testing compared to VD offspring, but no difference in response during fixed-ratio 1 or 3 testing. IHC results showed CS offspring had lower levels of TH-immunoreactivity in the NAc core and shell. These findings further support that delivery by CS has long-term neurodevelopmental effects, specifically in the brains reward system, and that CS offspring have decreased motivation toward food reward independent of deficits in learning.

neuroscience↗

The Neuroscience Multi-Omic Archive: A BRAIN Initiative resource for single-cell transcriptomic and epigenomic data from the mammalian brain

Scalable technologies to sequence the transcriptomes and epigenomes of single cells are transforming our understanding of cell types and cell states. The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative Cell Census Network (BICCN) is applying these technologies at unprecedented scale to map the cell types in the mammalian brain. In an effort to increase data FAIRness (Findable, Accessible, Interoperable, Reusable), the NIH has established repositories to make data generated by the BICCN and related BRAIN Initiative projects accessible to the broader research community. Here, we describe the Neuroscience Multi-Omic Archive (NeMO Archive; nemoarchive.org), which serves as the primary repository for genomics data from the BRAIN Initiative. Working closely with other BRAIN Initiative researchers, we have organized these data into a continually expanding, curated repository, which contains transcriptomic and epigenomic data from over 50 million brain cells, including single-cell genomic data from all of the major regions of the adult and prenatal human and mouse brains, as well as substantial single-cell genomic data from non-human primates. We make available several tools for accessing these data, including a searchable web portal, a cloud-computing interface for large-scale data processing (implemented on Terra, terra.bio), and a visualization and analysis platform, NeMO Analytics (nemoanalytics.org). KEY POINTSO_LIThe Neuroscience Multi-Omic Archive serves as the genomics data repository for the BRAIN Initiative. C_LIO_LIGenomic data from >50 million cells span all the major regions of the brains of humans and mice. C_LIO_LIWe provide a searchable web portal, a cloud-computing interface, and a data visualization platform. C_LI

genomics↗

Deploying genomics workflows on high performance computing (HPC) platforms: storage, memory, and compute considerations

Next Generation Sequencing (NGS) workloads largely consist of pipelines of tasks with heterogeneous compute, memory, and storage requirements. Identifying the optimal system configuration has historically required expertise in both system architecture and bioinformatics. This paper outlines infrastructure recommendations for one commonly used genomics workload based on extensive benchmarking and profiling, along with recommendations on how to tune genomics workflows for high performance computing (HPC) infrastructure. The demonstrated methodology and learnings can be extended for other genomics workloads and for other infrastructures such as the cloud.

bioinformatics↗

Prior hypoxia exposure enhances murine microglial inflammatory gene expression in vitro without concomitant H3K4me3 enrichment

Hypoxia is a component of multiple disorders, including stroke and sleep-disordered breathing, that often precede or are comorbid with neurodegenerative diseases. However, little is known about how hypoxia affects the ability of microglia, resident CNS macrophages, to respond to subsequent inflammatory challenges that are often present during neurodegenerative processes. We therefore tested the hypothesis that hypoxia would enhance or "prime" microglial pro-inflammatory gene expression in response to a later inflammatory challenge without programmatically increasing basal levels of pro-inflammatory cytokine expression. To test this, we pre-exposed immortalized N9 and primary microglia to hypoxia (1% O2) for 16 hrs and then challenged them with pro-inflammatory lipopolysaccharide (LPS) either immediately or 3-6 days following hypoxic exposure. We used RNA sequencing coupled with chromatin immunoprecipitation sequencing to analyze primed microglial inflammatory gene expression and modifications to histone H3 lysine 4 trimethylation (H3K4me3) at the promoters of primed genes. We found that microglia exhibited enhanced responses to LPS 3 days and 6 days post-hypoxia. Surprisingly however, the majority of primed genes were not enriched for H3K4me3 acutely following hypoxia exposure. Using the bioinformatics tool MAGICTRICKS and reversible pharmacological inhibition, we found that primed genes required the transcriptional activities of NF-B. These findings provide evidence that hypoxia pre-exposure could lead to persistent and aberrant inflammatory responses in the context of CNS disorders.

neuroscience↗