Biology subjects

Decourt, C.

Publications and source records attributed to Decourt, C..

3 recordsLinked to original sources

bioRxiv2026

Targeting Estrogen to the Brain via the Prodrug DHED does not Protect Against Metabolic Dysfunction in Obese, OVX mice.

Menopausal hormone therapy (MHT) is prescribed for climacteric symptoms including hot flushes and weight gain and contains estrogens such as 17 beta-estradiol (17{beta}E2). However, estrogen receptor activation by MHT may increase reproductive cancers and cardiovascular event risk in some people. As the protective metabolic effects of 17{beta}E2 are partly mediated through the arcuate nucleus of the hypothalamus, restricting 17{beta}E2 actions to the brain could serve as a safer mechanism of MHT. 10{beta},17{beta}-Dihydroxyestra-1,4-dien-3-one (DHED) is a prodrug of 17{beta}E2 which is enzymatically converted to the parent hormone exclusively within the brain. DHED has demonstrated positive benefit in rodent models of centrally-mediated maladies including hot flushes, depression and cognitive decline, without peripheral hormonal burden. Therefore, we hypothesized that DHED treatment in obese female mice would act within the hypothalamus to provide the same beneficial metabolic effects as 17{beta}E2. Female mice were ovariectomized, placed on a high fat diet and split into either control, DHED, or 17{beta}E2 treatment groups. Body weight, uterus weight and glucose tolerance were recorded along with gonadal hormone receptor expression in the brain. Delivery of DHED at a similar dose as 17{beta}E2 failed to improve metabolic parameters or recapitulate the hypothalamic responses induced by 17{beta}E2. Delivery of DHED at higher doses, which elicited estrogen-like actions within the brain, still failed to improve metabolic health. Our findings suggest that peripheral actions, in addition to hypothalamic targets, may be required to mediate 17{beta}E2s protective effects on metabolism and that brain-targeted MHT may be unsuitable for improving metabolic health during menopause.

physiology↗

bioRxiv2024

Proteomics-based characterization of ribosome heterogeneity in adult mouse organs

While long thought to be invariable in all cellular organisms, evidence has emerged that the translation process, i.e. protein assembly from mRNA sequence decoding, is regulated by variable features of the translation machinery. Notably, ribosomes, the functional units of protein synthesis, display variations in their composition, depending on the developmental stage, cell type or physiopathological context, thus providing a new level of actionable regulation of gene expression. Yet, a comprehensive map of the heterogeneity of ribosome composition in ribosomal proteins (RPs) in different organs and tissues is not available. In this work, we explored tissue-specific ribosome heterogeneity using mass spectrometry-based quantitative proteomic characterization of ribosomal fractions purified from 14 adult mouse organs and tissues. We performed crossed clustering and statistical analyses of RP composition to highlight stable, variable and tissue-specific RPs across organs and tissues. Focusing on specific RPs, we validated their relative abundance with a targeted proteomic approach, which gave further insight into the tissue-specific ribosome RP signature. Finally, we investigated the origin of RP variations in ribosome fraction of the different tissues, by comparing RP relative abundances in our proteomic dataset and in three independent transcriptomic datasets. Interestingly, we found that, in some tissues, the RP abundance in purified ribosomes does not always correlate with the corresponding RP transcript level, arguing for a translational regulation of RP expression, and/or a regulated incorporation of RPs into ribosomes. Altogether, our data support the notion of a tissue-specific RP signature of ribosomes, which opens avenues to study how specific ribosomal composition provides an additional level of regulation to control gene expression in different tissues and organs.

biochemistry↗

bioRxiv2022

The RSK-RPS6 axis controls the preconditioning effect and induces spinal cord regeneration

Unlike immature neurons and neurons from the peripheral nervous system (PNS), mature neurons from the central nervous system (CNS) cannot regenerate after injury. In the past 15 years, huge progress has been made to identify molecules and pathways necessary for neuroprotection and/or regeneration after CNS injury. In most regenerative models, phosphorylated ribosomal protein S6 (p-RPS6) is upregulated in neurons, which is often associated with an activation of the mTOR pathway. However, the exact contribution of post-translational modifications of this ribosomal protein in CNS regeneration remains elusive. In this study, we demonstrate that RPS6 phosphorylation is essential for PNS and CNS regeneration. We show that this phosphorylation is induced during the preconditioning effect in dorsal root ganglion (DRG) neurons, and that it is controlled by the p90S6 kinase RSK2. Our results reveal that RSK2 controls the preconditioning effect and that the RSK2-RPS6 axis is key for this process, as well as for PNS regeneration. Finally, we demonstrate that RSK2 promotes CNS regeneration in the dorsal column and allows functional recovery. Our data establish the critical role of RPS6 phosphorylation controlled by RSK2 in CNS regeneration and give new insights into the mechanism related to axon growth and circuit formation after traumatic lesion.

neuroscience↗