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Environmentally enriched pigs have transcriptional profiles consistent with neuroprotective effects and reduced microglial activity.

ABSTRACT: Environmental enrichment (EE) is widely used to study the effects of external factors on brain development, function and health in rodent models, but very little is known of the effects of EE on the brain in a large animal model such as the pig. Twenty-four young pigs (aged 5 weeks at start of study, 1:1 male: female ratio) were housed in environmentally enriched (EE) pens and provided with additional enrichment stimulation (a bag filled with straw) once daily. Litter, weight and sex matched controls n= (24) were housed in barren (B) conditions. Behaviour was recorded on alternate days from study day 10. After 21 days, RNA-sequencing of the frontal cortex of male piglets culled one hour after the enrichment stimulation, but not those at 4?h after stimulation, showed upregulation of genes involved in neuronal activity and synaptic plasticity in the EE compared to the B condition. This result is mirrored in the behavioural response to the stimulation which showed a peak in activity around the 1?h time-point. By contrast, EE piglets displayed a signature consistent with a relative decrease in microglial activity compared to those in the B condition. These results confirm those from rodents, suggesting that EE may also confer neuronal health benefits in large mammal models, through a potential relative reduction in neuroinflammatory process and increase in neuroprotection driven by an enrichment-induced increase in behavioural activity.

SUBMITTER: Brown SM

PROVIDER: S-EPMC6002610 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Environmentally enriched pigs have transcriptional profiles consistent with neuroprotective effects and reduced microglial activity.

Brown S M SM Bush S J SJ Summers K M KM Hume D A DA Lawrence A B AB

Behavioural brain research 20180517

Environmental enrichment (EE) is widely used to study the effects of external factors on brain development, function and health in rodent models, but very little is known of the effects of EE on the brain in a large animal model such as the pig. Twenty-four young pigs (aged 5 weeks at start of study, 1:1 male: female ratio) were housed in environmentally enriched (EE) pens and provided with additional enrichment stimulation (a bag filled with straw) once daily. Litter, weight and sex matched con ...[more]

PMID: 29778628

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Project description:BackgroundIn the healthy central nervous system (CNS), microglia are found in a homeostatic state and peripheral macrophages are absent from the brain. Microglia play key roles in maintaining CNS homeostasis and acting as first responders to infection and inflammation, and peripheral macrophages infiltrate the CNS during neuroinflammation. Due to their distinct origins and functions, discrimination between these cell populations is essential to the comprehension of neuroinflammatory disorders. Studies comparing the gene profiles of microglia and peripheral macrophages, or macrophages in vitro-derived from bone marrow, under non-infectious conditions of the CNS, have revealed valuable microglial-specific genes. However, studies comparing gene profiles between CNS-infiltrating macrophages and microglia, when both are isolated from the CNS during viral-induced neuroinflammation, are lacking.MethodsWe isolated, via flow cytometry, microglia and infiltrating macrophages from the brains of Theiler's murine encephalomyelitis virus-infected C57BL/6 J mice and used RNA-Seq, followed by validation with qPCR, to examine the differential transcriptional profiles of these cells. We utilized primary literature defining subcellular localization to determine whether or not particular proteins extracted from the transcriptional profiles were expressed at the cell surface. The surface expression and cellular specificity of triggering receptor expressed on myeloid cells 1 (TREM-1) protein were examined via flow cytometry. We also examined the immune response gene profile within the transcriptional profiles of these isolated microglia and infiltrating macrophages.ResultsWe have identified and validated new microglial- and macrophage-specific genes, encoding cell surface proteins, expressed at the peak of neuroinflammation. TREM-1 protein was confirmed to be expressed by infiltrating macrophages, not microglia, at the peak of neuroinflammation. We also identified both unique and redundant immune functions, through examination of the immune response gene profiles, of microglia and infiltrating macrophages during neurotropic viral infection.ConclusionsThe differential expression of cell surface-specific genes during neuroinflammation can potentially be used to discriminate between microglia and macrophages as well as provide a resource that can be further utilized to target and manipulate specific cell responses during neuroinflammation.

Project description:This research evaluates the performance of areal interpolation coupled with dasymetric refinement to estimate different demographic attributes, namely population sub-groups based on race, age structure and urban residence, within consistent census tract boundaries from 1990 to 2010 in Massachusetts. The creation of such consistent estimates facilitates the study of the nuanced micro-scale evolution of different aspects of population, which is impossible using temporally incompatible small-area census geographies from different points in time. Various unexplored ancillary variables, including the Global Human Settlement Layer (GHSL), the National Land-Cover Database (NLCD), parcels, building footprints and the proprietary ZTRAX® dataset are utilized for dasymetric refinement prior to areal interpolation to examine their effectiveness in improving the accuracy of multi-temporal population estimates. Different areal interpolation methods including Areal Weighting (AW), Target Density Weighting (TDW), Expectation Maximization (EM) and its data-extended approach are coupled with different dasymetric refinement scenarios based on these ancillary variables. The resulting consistent small area estimates of white and black subpopulations, people of age 18-65 and urban population show that dasymetrically refined areal interpolation is particularly effective when the analysis spans a longer time period (1990-2010 instead of 2000-2010) and the enumerated population is sufficiently large (e.g., counts of white vs. black). The results also demonstrate that current census-defined urban areas overestimate the spatial distribution of urban population and dasymetrically refined areal interpolation improves estimates of urban population. Refined TDW using building footprints or the ZTRAX® dataset outperforms all other methods. The implementation of areal interpolation enriched by dasymetric refinement represents a promising strategy to create more reliable multi-temporal and consistent estimates of different population subgroups and thus demographic compositions. This methodological foundation has the potential to advance micro-scale modeling of various subpopulations, particularly urban population to inform studies of urbanization and population change over time as well as future population projections.

Dataset Information

Environmentally enriched pigs have transcriptional profiles consistent with neuroprotective effects and reduced microglial activity.

Publications

Environmentally enriched pigs have transcriptional profiles consistent with neuroprotective effects and reduced microglial activity.

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