Neuropeptide

Résumé

Un neuropeptide est un type d'hormone, plus précisément un peptide sécrété par un neurone et ayant essentiellement une fonction de neuromodulateur. Ce sont des polypeptides ou de petites protéines formés de quelques acides aminés jusqu'à plusieurs centaines (191 pour l'hormone de croissance). Ils se lient généralement à un récepteur couplé à une protéine G capable, lorsqu'elle est activée, de déclencher une chaîne de réactions mettant en œuvre plusieurs effecteurs pouvant moduler finement la transmission du message. La transmission de l'information est plus lente que via un récepteur-canal qui, lui, peut rapidement déclencher un potentiel d'action postsynaptique (comme l'acétylcholine ou le glutamate) ou l'inhiber (GABA). Plus de cent neuropeptides ont été décrits. Ils interviennent dans la régulation du sommeil, de l'éveil, de l'émotion, de la récompense, de la douleur, de l'apprentissage et de la mémoire. Leur étude est relativement récente et beaucoup de choses restent à découv

Source officielle

https://fr.wikipedia.org/wiki/Neuropeptide

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Les neurotransmetteurs, ou neuromédiateurs, sont des composés chimiques libérés par les neurones (et parfois par les cellules gliales) agissant sur d'autres neurones, appelés neurones postsynaptiques,

thumb|250px|Vue tridimensionnelle de l'hypothalamus (en rouge). L'hypothalamus (du grec : ὑπό, hypo = dessous et θάλαμος, thálamos = chambre, cavité) est une structure du système nerveux central, sit

vignette|Exemple de peptide. vignette|Exemple de peptide. vignette|Exemple de peptide. Un peptide est un polymère d’acides aminés reliés entre eux par des liaisons peptidiques. Il existe une énorme

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Hypocretin/orexin (HCRT) and melanin concentrating hormone (MCH) neuropeptides are exclusively produced by the lateral hypothalamus and play important roles in sleep, metabolism, reward, and motivation. Loss of HCRT (ligands or receptors) causes the sleep disorder narcolepsy with cataplexy in humans and in animal models. How these neuropeptides are produced and involved in diverse functions remain unknown. Here, we developed methods to sort and purify HCRT and MCH neurons from the mouse late embryonic hypothalamus. RNA sequencing revealed key factors of fate determination for HCRT (Peg3, Ahr1, Six6, Nr2f2, and Prrx1) andMCH (Lmx1, Gbx2, and Peg3) neurons. Loss of Peg3 in mice significantly reduces HCRT and MCH cell numbers, while knock-down of a Peg3 ortholog in zebrafish completely abolishes their expression, resulting in a 2-fold increase in sleep amount. We also found that loss of HCRT neurons in Hcrt-ataxin-3 mice results in a specific 50% decrease in another orexigenic neuropeptide, QRFP, that might explain the metabolic syndrome in narcolepsy. The transcriptome results were used to develop protocols for the production of HCRT and MCH neurons from induced pluripotent stem cells and ascorbic acid was found necessary for HCRT and BMP7 for MCH cell differentiation. Our results provide a platform to understand the development and expression of HCRT and MCH and their multiple functions in health and disease.

PNAS2019

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Stress Impacts the Regulation Neuropeptides in the Rat Hippocampus and Prefrontal Cortex

Laura Lozano Montes, Gregor Rainer, Nan Zhao

Adverse life experience increases the lifetime risk to several stress-related psychopathologies, such as anxiety or depressive–like symptom following stress in adulthood. However, the neurochemical modulations triggered by stress have not been fully characterized. Neuropeptides play an important role as signaling molecules that contribute to physiological regulation and have been linked to neurological and psychiatric diseases. However, little is known about the influence of stress on neuropeptide regulation in the brain. Here, we have performed an exploratory study of how neuropeptide expression at adulthood is modulated by experiencing a period of multiple stressful experiences. We have targeted hippocampus and prefrontal cortex (PFC) brain areas, which have previously been shown to be modulated by stressors, employing a targeted Liquid Chromatography-Mass Spectrometry (LC-MS) based approach that permits broad peptide coverage with high sensitivity. We found that in the hippocampus, Met-enkephalin, Met-enkephalin-Arg-Phe and Met-enkephalin-Arg-Gly-Leu were up regulated, while Leu-enkephalin and Little SAAS were down regulated after stress. In the PFC area, Met-enkephalin-Arg-Phe, Met-enkephalin-Arg-Gly-Leu, peptide PHI-27, somatostatin-28 (AA1-12) and Little SAAS were all down regulated. This systematic evaluation of neuropeptide alterations in hippocampus and PFC suggests that stressor impact neuropeptides and that neuropeptide regulation is brain area specific. These findings suggest several potential peptide candidates, which warrant further investigations in terms of correlation with depression-associated behaviors.

2018

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Molecular Imaging of Biopolymers Enabled by Electrospray-Ion Beam Deposition

Sabine Abb

Biomolecular functional complexes often serve as inspiration for the development of artificial molecular nanostructures. The functionality of the biomolecular structures is based on complex and adaptable binding motifs that have evolved over billions of years. The detailed understanding of the underlying interactions is pivotal for the rational design and development of new materials, but often difficult to achieve as it requires submolecular resolution. In this thesis, I show how the molecular imaging of biopolymers by scanning tunneling microscopy (STM) and low-energy electron holography (LEEH) contributes to deciphering the structures and the respective binding motifs. These high-resolution imaging methods only perform well on surfaces in ultra-high vacuum (UHV) and for chemically identified species. Thus, electrospray ion beam deposition (ES-IBD) is essential for the controlled deposition for non-volatile species in UHV. The first part of the thesis focuses on the characterization of the disaccharides as smallest representatives of polysaccharides. Deposited by ES-IBD, the first high-resolution STM characterization of this molecular class on a surface in UHV is performed. The disaccharides sucrose and trehalose can be distinguished as they exhibit specific self-assembly motifs and are imaged differently. For sucrose, the two monosaccharide building blocks are resolved, highlighting the impact that high-resolution imaging by STM might have in the future for the clarification of unknown sequences by identifying branching points. In the second part of the thesis, peptides are employed as building blocks for novel structures on the surface. A combined approach of STM imaging with modeling by MD and DFT is applied to identify the binding motifs and the underlying specific interactions. Understanding of the binding motifs of the decapeptide angiotensin-I on Au(111) enables the design of a long-ranged ordered honeycomb network by manipulating the sequence to the octapeptide angiotensin-II. Representing a further binding motif that is often employed in catalytically active peptides, peptide-metal complexes are investigated on the surface showing a significant influence on the peptide structure. Based on the long-range ordered network for the pure angiotensin-II, we find that the introduction of a metal coordination center makes the molecular structure more compact and thus reduces the intermolecular interaction sites yielding an assembly of reduced dimensionality. In the last part, the proof of principle is presented that LEEH, empowered by the ES-IBD sample preparation, is able to image single folded proteins on free stranding ultra-clean graphene and might therefore provide protein structures without averaging. To this end, native mass spectrometry is adopted to ES-IBD for the deposition of folded proteins (cytochrome C, bovine serum albumin) and protein complexes (hemoglobin). In conclusion, the versatile deposition of biopolymers by ES-IBD enables UHV based single molecule imaging techniques for a range of different samples, starting from imaging the sequence and characterizing 2D nanostructures of biomolecules by STM to 3D folded protein complexes imaged by LEEH. High-resolution imaging opens new perspectives for structure determination, such as the branching points of polysaccharides and the 3D structure of single proteins. Moreover, a detailed understanding of binding motifs is crucial for the rational design of new nanostructures.

EPFL2017

Chargement

Molecular Imaging of Biopolymers Enabled by Electrospray-Ion Beam Deposition

Sabine Abb

EPFL2017