Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Elevated protein synthesis in microglia causes autism-like synaptic and behavioral aberrations.

Nature communications | 2020

Mutations that inactivate negative translation regulators cause autism spectrum disorders (ASD), which predominantly affect males and exhibit social interaction and communication deficits and repetitive behaviors. However, the cells that cause ASD through elevated protein synthesis resulting from these mutations remain unknown. Here we employ conditional overexpression of translation initiation factor eIF4E to increase protein synthesis in specific brain cells. We show that exaggerated translation in microglia, but not neurons or astrocytes, leads to autism-like behaviors in male mice. Although microglial eIF4E overexpression elevates translation in both sexes, it only increases microglial density and size in males, accompanied by microglial shift from homeostatic to a functional state with enhanced phagocytic capacity but reduced motility and synapse engulfment. Consequently, cortical neurons in the mice have higher synapse density, neuroligins, and excitation-to-inhibition ratio compared to control mice. We propose that functional perturbation of male microglia is an important cause for sex-biased ASD.

Pubmed ID: 32286273 RIS Download

Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK105954
  • Agency: NIMH NIH HHS, United States
    Id: R21 MH108046
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK103335
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH108519

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

View all literature mentions

Fiji (tool)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

View all literature mentions

Cell Signaling Technology (tool)

RRID:SCR_004431

Privately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.

View all literature mentions

Systems Transcriptional Activity Reconstruction (tool)

RRID:SCR_005622

A next-generation web-based application that aims to provide an integrated solution for both visualization and analysis of deep-sequencing data, along with simple access to public datasets.

View all literature mentions

Bioconductor (tool)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

View all literature mentions

Thermo Fisher Scientific (tool)

RRID:SCR_008452

Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.

View all literature mentions

TrakEM2 (tool)

RRID:SCR_008954

An ImageJ plugin for morphological data mining, three-dimensional modeling and image stitching, registration, editing and annotation. Two independent modalities exist: either XML-based projects, working directly with the file system, or database-based projects, working on top of a local or remote PostgreSQL database. What can you do with it? * Semantic segmentation editor: order segmentations in tree hierarchies, whose template is exportable for reuse in other, comparable projects. * Model, visualize and export 3D. * Work from your laptop on your huge, remote image storage. * Work with an endless number of images, limited only by the hard drive capacity. Dozens of formats supported thanks to LOCI Bioformats and ImageJ. * Import stacks and even entire grids (montages) of images, automatically stitch them together and homogenize their histograms for best montaging quality. * Add layers conveniently. A layer represents, for example, one 50 nm section (for TEM) or a confocal section. Each layer has its own Z coordinate and thickness, and contains images, labels, areas, nodes of 3d skeletons, profiles... * Insert layer sets into layers: so your electron microscopy serial sections can live inside your optical microscopy sections. * Run any ImageJ plugin on any image. * Measure everything: areas, volumes, pixel intensities, etc. using both built-in data structures and segmentation types, and standard ImageJ ROIs. And with double dissectors! * Visualize RGB color channels changing the opacity of each on the fly, non-destructively. * Annotate images non-destructively with floating text labels, which you can rotate/scale on the fly and display in any color. * Montage/register/stitch/blend images manually with transparencies, semiautomatically, or fully automatically within and across sections, with translation, rigid, similarity and affine models with automatically extracted SIFT features. * Correct the lens distortion present in the images, like those generated in transmission electron microscopy. * Add alpha masks to images using ROIs, for example to split images in two or more parts, or to remove the borders of an image or collection of images. * Model neuronal arbors with 3D skeletons (with areas or radiuses), and synapses with connectors. * Undo all steps. And much more...

View all literature mentions

Millipore (tool)

RRID:SCR_008983

An Antibody supplier

View all literature mentions

Sigma-Aldrich (tool)

RRID:SCR_008988

American chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.

View all literature mentions

FISHER (tool)

RRID:SCR_009181

THIS RESOURCE IS NO LONGER IN SERVICE, documented on February 1st, 2022. Software application for genetic analysis of classical biometric traits like blood pressure or height that are caused by a combination of polygenic inheritance and complex environmental forces. (entry from Genetic Analysis Software)

View all literature mentions

Abcam (tool)

RRID:SCR_012931

A commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.

View all literature mentions

New England Biolabs (tool)

RRID:SCR_013517

An Antibody supplier

View all literature mentions

Synaptic Systems (tool)

RRID:SCR_013612

An Antibody supplier

View all literature mentions

Wako (tool)

RRID:SCR_013651

An Antibody supplier

View all literature mentions

HEK293 (tool)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

View all literature mentions