Summary of project PR001682

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, 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.


Project ID: PR001682
Project DOI:doi: 10.21228/M8914J
Project Title:Loss of microglial MCT4 leads to defective synaptic pruning and anxiety-like behavior in mice
Project Summary:Microglia, 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
Laboratory:Lab of Angelo D'Alessandro in collaboration with lab of Rosa Paolicelli (Univ of Lausanne)
Last Name:Haines
First Name:Julie
Address:12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA

Summary of all studies in project PR001682

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST002714 Loss of microglial MCT4 leads to defective synaptic pruning and anxiety-like behavior in mice Mus musculus University of Colorado Denver MS 2023-06-22 1 20 Uploaded data (1.3G)*