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Gene expression analysis in Fmr1KO mice identifies an immunological signature in brain tissue and mGluR5-related signaling in primary neuronal cultures

Overview of attention for article published in Molecular Autism, December 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (85th percentile)
  • Average Attention Score compared to outputs of the same age and source

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1 blog
twitter
6 tweeters

Citations

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12 Dimensions

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52 Mendeley
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Title
Gene expression analysis in Fmr1KO mice identifies an immunological signature in brain tissue and mGluR5-related signaling in primary neuronal cultures
Published in
Molecular Autism, December 2015
DOI 10.1186/s13229-015-0061-9
Pubmed ID
Authors

Daria Prilutsky, Alvin T. Kho, Nathan P. Palmer, Asha L. Bhakar, Niklas Smedemark-Margulies, Sek Won Kong, David M. Margulies, Mark F. Bear, Isaac S. Kohane

Abstract

Fragile X syndrome (FXS) is a neurodevelopmental disorder whose biochemical manifestations involve dysregulation of mGluR5-dependent pathways, which are widely modeled using cultured neurons. In vitro phenotypes in cultured neurons using standard morphological, functional, and chemical approaches have demonstrated considerable variability. Here, we study transcriptomes obtained in situ in the intact brain tissues of a murine model of FXS to see how they reflect the in vitro state. We used genome-wide mRNA expression profiling as a robust characterization tool for studying differentially expressed pathways in fragile X mental retardation 1 (Fmr1) knockout (KO) and wild-type (WT) murine primary neuronal cultures and in embryonic hippocampal and cortical murine tissue. To study the developmental trajectory and to relate mouse model data to human data, we used an expression map of human development to plot murine differentially expressed genes in KO/WT cultures and brain. We found that transcriptomes from cell cultures showed a stronger signature of Fmr1KO than whole tissue transcriptomes. We observed an over-representation of immunological signaling pathways in embryonic Fmr1KO cortical and hippocampal tissues and over-represented mGluR5-downstream signaling pathways in Fmr1KO cortical and hippocampal primary cultures. Genes whose expression was up-regulated in Fmr1KO murine cultures tended to peak early in human development, whereas differentially expressed genes in embryonic cortical and hippocampal tissues clustered with genes expressed later in human development. The transcriptional profile in brain tissues primarily centered on immunological mechanisms, whereas the profiles from cell cultures showed defects in neuronal activity. We speculate that the isolation and culturing of neurons caused a shift in neurological transcriptome towards a "juvenile" or "de-differentiated" state. Moreover, cultured neurons lack the close coupling with glia that might be responsible for the immunological phenotype in the intact brain. Our results suggest that cultured cells may recapitulate an early phase of the disease, which is also less obscured with a consequent "immunological" phenotype and in vivo compensatory mechanisms observed in the embryonic brain. Together, these results suggest that the transcriptome of cultured primary neuronal cells, in comparison to whole brain tissue, more robustly demonstrated the difference between Fmr1KO and WT mice and might reveal a molecular phenotype, which is typically hidden by compensatory mechanisms present in vivo. Moreover, cultures might be useful for investigating the perturbed pathways in early human brain development and genes previously implicated in autism.

Twitter Demographics

The data shown below were collected from the profiles of 6 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Unknown 51 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 25%
Student > Ph. D. Student 12 23%
Student > Doctoral Student 4 8%
Student > Master 4 8%
Student > Postgraduate 3 6%
Other 8 15%
Unknown 8 15%
Readers by discipline Count As %
Neuroscience 15 29%
Agricultural and Biological Sciences 9 17%
Biochemistry, Genetics and Molecular Biology 6 12%
Psychology 5 10%
Medicine and Dentistry 4 8%
Other 5 10%
Unknown 8 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 December 2019.
All research outputs
#2,657,070
of 19,960,113 outputs
Outputs from Molecular Autism
#274
of 623 outputs
Outputs of similar age
#57,465
of 392,573 outputs
Outputs of similar age from Molecular Autism
#31
of 52 outputs
Altmetric has tracked 19,960,113 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 623 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 28.8. This one has gotten more attention than average, scoring higher than 56% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 392,573 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 85% of its contemporaries.
We're also able to compare this research output to 52 others from the same source and published within six weeks on either side of this one. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.