Analysis of Astroglial Secretomic Profile in the Mecp2-Deficient Male Mouse Model of Rett Syndrome

• Published in: International journal of molecular sciences 2021-04, Vol.22 (9), p.4316
• Main Authors: Ehinger, Yann, Matagne, Valerie, Cunin, Valérie, Borloz, Emilie, Seve, Michel, Bourgoin-Voillard, Sandrine, Borges-Correia, Ana, Villard, Laurent, Roux, Jean-Christophe
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes; Astrocytes - metabolism; Astrocytes - physiology; Central nervous system; Dendritic branching; Dendritic structure; Deregulation; Disease Models, Animal; DNA methylation; Gene Deletion; Gene expression; Gene Expression Regulation; Genetics; Human health and pathology; iTRAQ quantitative proteomic approach; Life Sciences; Male; Mass spectrometry; Mecp2; MeCP2 protein; Metabolism; Methyl-CpG binding protein; Methyl-CpG-Binding Protein 2 - genetics; Mice; Morphology; Mutation; Nerve Tissue Proteins - metabolism; neuronal arborization; Neurons; Neurosecretion; Pathophysiology; Phenotypes; Proteins; Proteomics; Rett syndrome; Rett Syndrome - genetics; Rett Syndrome - metabolism; Rett Syndrome - physiopathology; Scientific imaging; secretome; Transcription; Western blotting
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22094316

Mutations in the X-linked gene are responsible for Rett syndrome (RTT), a severe neurological disorder. MECP2 is a transcriptional modulator that finely regulates the expression of many genes, specifically in the central nervous system. Several studies have functionally linked the loss of MECP2 in astrocytes to the appearance and progression of the RTT phenotype in a non-cell autonomous manner and mechanisms are still unknown. Here, we used primary astroglial cells from -deficient (KO) pups to identify deregulated secreted proteins. Using a differential quantitative proteomic analysis, twenty-nine proteins have been identified and four were confirmed by Western blotting with new samples as significantly deregulated. To further verify the functional relevance of these proteins in RTT, we tested their effects on the dendritic morphology of primary cortical neurons from KO mice that are known to display shorter dendritic processes. Using Sholl analysis, we found that incubation with Lcn2 or Lgals3 for 48 h was able to significantly increase the dendritic arborization of KO neurons. To our knowledge, this study, through secretomic analysis, is the first to identify astroglial secreted proteins involved in the neuronal RTT phenotype in vitro, which could open new therapeutic avenues for the treatment of Rett syndrome.