In this section, you can access to the latest technical information related to the FUTURE project topic.

Phenotype microarrays reveal metabolic dysregulations of neurospheres derived from embryonic Ts1Cje mouse model of Down syndrome

Abstract

Down syndrome (DS), is the most common cause of intellectual disability, and is characterized by defective neurogenesis during perinatal development. To identify metabolic aberrations in early neurogenesis, we profiled neurospheres derived from the embryonic brain of Ts1Cje, a mouse model of Down syndrome. High-throughput phenotypic microarray revealed a significant decrease in utilisation of 17 out of 367 substrates and significantly higher utilisation of 6 substrates in the Ts1Cje neurospheres compared to controls. Specifically, Ts1Cje neurospheres were less efficient in the utilisation of glucose-6-phosphate suggesting a dysregulation in the energy-producing pathway. T Cje neurospheres were significantly smaller in diameter than the controls. Subsequent preliminary study on supplementation with 6-phosphogluconic acid, an intermediate of glucose-6-phosphate metabolism, was able to rescue the Ts1Cje neurosphere size. This study confirmed the perturbed pentose phosphate pathway, contributing to defects observed in Ts1Cje neurospheres. We show for the first time that this comprehensive energetic assay platform facilitates the metabolic characterisation of Ts1Cje cells and confirmed their distinguishable metabolic profiles compared to the controls.

» Author: Eryse Amira Seth,  Han-Chung Lee,  Hadri Hadi bin Md Yusof,  Norshariza Nordin,  Yoke Kqueen Cheah,  Eric Tatt Wei Ho,  King-Hwa Ling,  Pike-See Cheah

» Reference: https://doi.org/10.1371/journal.pone.0236826

» Publication Date: 30/07/2020

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