MassIVE MSV000098524

Partial Public

Blood glutamine is critical for neurotransmitter synthesis, energy homeostasis, and synaptogenesis in the developing brain

Description

The main goal of this study was how the brain obtains glutamine during the early postnatal period, when the expression of glutamine synthetase is low. We found that early postnatal mice maintain their brain glutamine levels by importing glutamine from the blood. We identified the Slc38a3 transporter as a primary transendothelial glutamine transporter at brain capillaries. Mice with selective knockout of Slc38a3 (Slc38a3-cKO) in endothelial cells exhibit a significant decrease in the influx of glutamine and histidine through the BBB at postnatal day 11 (P11). This is accompanied by a significant decrease in brain glutamine and histidine levels, along with secondary reductions in essential amino acids that are not substrates of Slc38a3. Slc38a3-cKO mice also exhibit postnatal/progressive microcephaly, similar to that observed in patients with mutations in Slc38a3. Slc38a3-cKO mice exhibit behavioral deficits, metabolic impairments, and synaptic alterations at P11. [doi:10.25345/C5HX16391] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Slc38a3 ; DatasetType:Metabolomics

Contact

Principal Investigators:
(in alphabetical order)
Herman Wolosker, Technion, Israel
Submitting User: vinna
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