Gpr158 mediates osteocalcin's regulation of cognition

That osteocalcin (OCN) is necessary for hippocampal-dependent memory and to prevent anxiety-like behaviors raises novel questions. One question is to determine whether OCN is also sufficient to improve these behaviors in wild-type mice, when circulating levels of OCN decline as they do with age. Here we show that the presence of OCN is necessary for the beneficial influence of plasma from young mice when injected into older mice on memory and that peripheral delivery of OCN is sufficient to improve memory and decrease anxiety-like behaviors in 16-mo-old mice. A second question is to identify a receptor transducing OCN signal in neurons. Genetic, electrophysiological, molecular, and behavioral assays identify Gpr158, an orphan G protein-coupled receptor expressed in neurons of the CA3 region of the hippocampus, as transducing OCN's regulation of hippocampal-dependent memory in part through inositol 1,4,5-trisphosphate and brain-derived neurotrophic factor. These results indicate that exogenous OCN can improve hippocampal-dependent memory in mice and identify molecular tools to harness this pathway for therapeutic purposes

Analysis of PTH and PTHrp influence in regulating the control of energy balance by the central nervous system

Résumé confidentielConfidential abstrac

Pivotal roles of TRPV1 channel and Nrf2 factor in green light modulation of keratinocyte inflammatory response

ABSTRACT: Photobiomodulation (PBM) is emerging as a promising non-invasive approach for managing inflammatory skin conditions. However, its precise molecular mechanisms, especially within the green light spectrum, remain elusive. In this study, we investigated the anti-inflammatory mechanisms of 520 nm green light in primary human keratinocytes (KCs) exposed to the contact sensitizer 2,4-dinitrochlorobenzene (DNCB). Our data revealed that green light effectively reduces the mRNA expression of pro-inflammatory cytokines IL-6, IL-8, and TNF-α, comparably to the effect of dexamethasone, a conventional anti-inflammatory agent. As Nuclear factor erythroid-2-related factor 2 (Nrf2) is involved in the red light response, we explored Nrf2′s role in green light anti-inflammatory activity. Green light exposure activated the Nrf2 pathway, leading to Nrf2 increased accumulation in KCs and the induction of Nrf2 target genes, including HO-1 and GCLC. Invalidation of Nrf2 with si-RNA diminished the green light's regulatory effect, indicating Nrf2′s essential role in the green light's anti-inflammatory action. As the Transient Receptor Potential Vanilloid 1 (TRPV1) channel is a potential target for green light, we investigated its role in PBM response. Blocking TRPV1 with capsazepine (CPZ) abolished the anti-inflammatory effect of green light and prevented the upregulation of Nrf2 target genes. This finding highlights TRPV1′s integral role in green light beneficial activity via the activation of the Nrf2 pathway. Overall, our study identifies TRPV1 and Nrf2 as critical players in the green light response, highlighting the versatility of PBM in controlling skin inflammation

Identification of biological targets for argon

CERVOXYNational audienc

Identification of biological targets for argon

CERVOXYNational audienc

Identification of biological targets for argon

CERVOXYInternational audienc

Identification of biological targets for argon

CERVOXYInternational audienc

Identification of biological targets for argon

CERVOXYNational audienc

A method for the identification of potentially bioactive argon binding sites in protein families

CERVOXYInternational audienceArgon belongs to the group of chemically inert noble gases, which display a remarkable spectrum of clinically useful biological properties. In an attempt to better understand noble gases, notably argon's mechanism of action, we mined a massive noble gas modelling database which lists all possible noble gas binding sites in the proteins from the Protein Data Bank. We developed a method of analysis to identify amongst all predicted noble gas binding sites, the potentially relevant ones within protein families which are likely to be modulated by Ar. Our method consists in determining within structurally aligned proteins, the conserved binding sites whose shape, localization, hydrophobicity and binding energies are to be further examined. This method was applied to the analysis of two protein families where crystallographic noble gas binding sites have been experimentally determined. Our findings indicate that amongst the most conserved binding sites, either the most hydrophobic one and/or the site which has the best binding energy correspond to the crystallographic noble gas binding sites with the best occupancies, therefore the best affinity for the gas. This method will allow us to predict relevant noble gas binding sites that have potential pharmacological interest and thus potential Ar targets that will be prioritized for further studies including in vitro validation

Gpr158 mediates osteocalcin's regulation of cognition

That osteocalcin (OCN) is necessary for hippocampal-dependent memory and to prevent anxiety-like behaviors raises novel questions. One question is to determine whether OCN is also sufficient to improve these behaviors in wild-type mice, when circulating levels of OCN decline as they do with age. Here we show that the presence of OCN is necessary for the beneficial influence of plasma from young mice when injected into older mice on memory and that peripheral delivery of OCN is sufficient to improve memory and decrease anxiety-like behaviors in 16-mo-old mice. A second question is to identify a receptor transducing OCN signal in neurons. Genetic, electrophysiological, molecular, and behavioral assays identify Gpr158, an orphan G protein-coupled receptor expressed in neurons of the CA3 region of the hippocampus, as transducing OCN's regulation of hippocampal-dependent memory in part through inositol 1,4,5-trisphosphate and brain-derived neurotrophic factor. These results indicate that exogenous OCN can improve hippocampal-dependent memory in mice and identify molecular tools to harness this pathway for therapeutic purposes