Summary of Study ST002714

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001682. The data can be accessed directly via it's Project DOI: 10.21228/M8914J This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002714
Study TitleLoss of microglial MCT4 leads to defective synaptic pruning and anxiety-like behavior in mice
Study SummaryMicroglia, the innate immune cells of the central nervous system, actively participate in brain development by supporting neuronal maturation and refining synaptic connections. These cells are emerging as highly metabolically flexible, able to oxidize different energetic substrates to meet their energy demand. Lactate is particularly abundant in the brain, but whether microglia use it as a metabolic fuel has been poorly explored. Here we show that microglia can import lactate, and this is coupled with increased lysosomal acidification. In vitro, loss of the monocarboxylate transporter MCT4 in microglia prevents lactate-induced lysosomal modulation and leads to defective cargo degradation. Microglial depletion of MCT4 in vivo leads to impaired synaptic pruning, associated with increased excitation in hippocampal neurons, enhanced E/I ratio, vulnerability to seizures and anxiety-like phenotype. Overall, these findings show that selective disruption of the MCT4 transporter in microglia is sufficient to alter synapse refinement and to induce defects in brain development and adult behavior.
Institute
University of Colorado Denver
Last NameHaines
First NameJulie
Address12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA
Emailjulie.haines@cuanschutz.edu
Phone3037243339
Submit Date2023-05-24
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2023-06-22
Release Version1
Julie Haines Julie Haines
https://dx.doi.org/10.21228/M8914J
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id sex genetic status
SA2735427F KO
SA27354312F KO
SA27354415F KO
SA2735456F KO
SA27354611F KO
SA2735474BF WT
SA2735485BF WT
SA2735499F WT
SA2735502F WT
SA2735513BM KO
SA2735521BM KO
SA27355314M KO
SA27355410M KO
SA2735554M KO
SA2735561M KO
SA2735578M WT
SA2735582BM WT
SA2735593M WT
SA27356013M WT
SA2735615M WT
Showing results 1 to 20 of 20
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