Metabolomic fingerprint of mecp2-deficient mouse cortex: Evidence for a pronounced multi-facetted metabolic component in rett syndrome

Gocha Golubiani, Vincenzo Lagani, Revaz Solomonia, Michael Müller

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Using unsupervised metabolomics, we defined the complex metabolic conditions in the cortex of a mouse model of Rett syndrome (RTT). RTT, which represents a cause of mental and cognitive disabilities in females, results in profound cognitive impairment with autistic features, motor disabilities, seizures, gastrointestinal problems, and cardiorespiratory irregularities. Typical RTT originates from mutations in the X-chromosomal methyl-CpG-binding-protein-2 (Mecp2) gene, which encodes a transcriptional modulator. It then causes a deregulation of several target genes and metabolic alterations in the nervous system and peripheral organs. We identified 101 significantly deregulated metabolites in the Mecp2-deficient cortex of adult male mice, 68 were increased and 33 were decreased compared to wildtypes. Pathway analysis identified 31 mostly upregulated metabolic pathways, in particular carbohydrate and amino acid metabolism, key metabolic mitochondrial/ extramitochondrial pathways, and lipid metabolism. In contrast, neurotransmitter-signaling is dampened. This metabolic fingerprint of the Mecp2-deficient cortex of severely symptomatic mice provides further mechanistic insights into the complex RTT pathogenesis. The deregulated pathways that were identified—in particular the markedly affected amino acid and carbohydrate metabolism— confirm a complex and multifaceted metabolic component in RTT, which in turn signifies putative therapeutic targets. Furthermore, the deregulated key metabolites provide a choice of potential biomarkers for a more detailed rating of disease severity and disease progression.
Original languageEnglish (US)
Issue number9
StatePublished - Sep 1 2021
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-09-23

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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