Dopaminergic and serotonergic changes in rabbit fetal brain upon repeated gestational exposure to diesel engine exhaust.

Limited studies in humans and in animal models have investigated the neurotoxic risks related to a gestational exposure to diesel exhaust particles (DEP) on the embryonic brain, especially those regarding monoaminergic systems linked to neurocognitive disorders. We previously showed that exposure to DEP alters monoaminergic neurotransmission in fetal olfactory bulbs and modifies tissue morphology along with behavioral consequences at birth in a rabbit model. Given the anatomical and functional connections between olfactory and central brain structures, we further characterized their impacts in brain regions associated with monoaminergic neurotransmission.

Effect of environmental exposure to a maternally-learned odorant on anxiety-like behaviors at weaning in mice.

Early sensory experience, such as exposure to maternal or other environmental factors, is considered to influence neurocognitive development and behaviors. In many species, exposure to odorants during pregnancy or lactation impacts the morpho-functional development of the olfactory circuitry with changes in olfactory sensitivity, feeding behavior and food preferences at birth or later. However, few studies have investigated the impact of a perinatal exposure to odorants on the anxiety-like behavior of animals to stressfull stimuli.

Effect of Maternal Obesity and Preconceptional Weight Loss on Male and Female Offspring Metabolism and Olfactory Performance in Mice.

According to the "developmental origins of health and disease" (DOHaD) concept, maternal obesity predisposes the offspring to non-communicable diseases in adulthood. While a preconceptional weight loss (WL) is recommended for obese women, its benefits on the offspring have been poorly addressed. We evaluated whether preconceptional WL was able to reverse the adverse effects of maternal obesity in a mouse model, exhibiting a modification of foetal growth and of the expression of genes encoding epigenetic modifiers in liver and placenta.

Repeated gestational exposure to diesel engine exhaust affects the fetal olfactory system and alters olfactory-based behavior in rabbit offspring.

Background: Airborne pollution, especially from diesel exhaust (DE), is known to have a negative effect on the central nervous system in exposed human populations. However, the consequences of gestational exposure to DE on the fetal brain remain poorly explored, with various effects depending on the conditions of exposure, as well as little information on early developmental stages. We investigated the short-term effects of indirect DE exposure throughout gestation on the developing brain using a rabbit model.

Chronic perinatal odour exposure with heptaldehyde affects odour sensitivity and olfactory system homeostasis in preweaning mice.

Exposure to specific odorants in the womb during pregnancy or in the milk during early nursing is known to impact morpho-functional development of the olfactory circuitry of pups. This can be associated with a modification in olfactory sensitivity and behavioural olfactory-based preferences to the perinatally encountered odorants measured at birth, weaning or adult stage. Effects depend on a multitude of factors, such as odorant type, concentration, administration mode and frequency, as well as timing and mice strain.

Immunochemical strategy for quantification of G-coupled olfactory receptor proteins on natural nanovesicles.

Cell membrane proteins are involved in a variety of biochemical pathways and therefore constitute important targets for therapy and development of new drugs. Bioanalytical platforms and binding assays using these membrane protein receptors for drug screening or diagnostic require the construction of well-characterized liposome and lipid bilayer arrays that act as support to prevent protein denaturation during biochip processing. Quantification of the protein receptors in the lipid membrane arrays is a key issue in order to produce reproducible and well-characterized chips.

A novel platform based on immobilized histidine tagged olfactory receptors, for the amperometric detection of an odorant molecule characteristic of boar taint.

We report a dose-dependent detection of androstenone in solution, as one of the boar taint compounds, based on related OR7D4 olfactory receptors immobilized on a gold electrode through their 6-His tag and NTA-copper complex, as visualized through fluorescence microscopy. Square wave voltammetry (SWV) is for the first time, the method used to monitor the olfactory receptor/odorant recognition process. The relative variation of the Cu(I)-Cu(II) current peak increases linearly versus log (concentration of androstenone) from 10(-14)M to 10(-4)M, in buffer solution.

Mammalian olfactory receptors: molecular mechanisms of odorant detection, 3D-modeling, and structure-activity relationships.

This chapter describes the main characteristics of olfactory receptor (OR) genes of vertebrates, including generation of this large multigenic family and pseudogenization. OR genes are compared in relation to evolution and among species. OR gene structure and selection of a given gene for expression in an olfactory sensory neuron (OSN) are tackled.

Force measurements on natural membrane nanovesicles reveal a composition-independent, high Young's modulus.

Mechanical properties of nano-sized vesicles made up of natural membranes are crucial to the development of stable, biocompatible nanocontainers with enhanced functional, recognition and sensing capabilities. Here we measure and compare the mechanical properties of plasma and inner membrane nanovesicles ∼80 nm in diameter obtained from disrupted yeast Saccharomyces cerevisiae cells. We provide evidence of a highly deformable behaviour for these vesicles, able to support repeated wall-to-wall compressions without irreversible deformations, accompanied by a noticeably high Young's modulus (∼300 MPa) compared to that obtained for reconstituted artificial liposomes of similar size and approaching that of some virus particles.

A unique transcriptome at the brain-environment interface: local translation in the rat olfactory epithelium.

All olfactory epithelium cells, including rapidly self-renewing olfactory sensory neurons (OSN), are continuously subjected to external airborne aggressions. We hypothesized that the apical part of rat olfactory epithelia (AOE) could be the site of a local translation to be able to respond rapidly to external stimuli. We purified significant amounts of mRNAs from AOE.

Relationship between homo-oligomerization of a mammalian olfactory receptor and its activation state demonstrated by bioluminescence resonance energy transfer.

G-protein-coupled receptor homo-oligomerization has been increasingly reported. However, little is known regarding the relationship between activation of the receptor and its association/conformational states. The mammalian olfactory receptors (ORs) belong to the G protein-coupled receptor superfamily.

On a chip demonstration of a functional role for Odorant Binding Protein in the preservation of olfactory receptor activity at high odorant concentration.

The molecular mechanisms underlying odorant detection have been investigated using the chip based SPR technique by focusing on the dynamic interactions between transmembrane Olfactory Receptor OR1740, odorant ligands and soluble Odorant-Binding Protein (OBP-1F). The OR1740 present in the lipid bilayer of nanosomes derived from transformed yeasts specifically bound OBP-1F. The receptor preferential odorant ligand helional released bound OBP-1F from the OR-OBP complex, while unrelated odorants failed to do so.

Gold surface functionalization and patterning for specific immobilization of olfactory receptors carried by nanosomes.

There is substantial interest in engineering solid supports to achieve functional immobilization of membrane receptors both for investigation of their biological function and for the development of novel biosensors. Three simple and practical strategies for immobilization of a human olfactory receptor carried by nanosomes are presented. The basis of the functionalization of solid gold surfaces is a self-assembled monolayer (SAM) containing biotinyl groups.

A novel detection strategy for odorant molecules based on controlled bioengineering of rat olfactory receptor I7.

In this study, we report a dose-dependent detection of odorant molecules in solution by rat olfactory receptor I7 (OR I7) in its membrane fraction. The OR I7 is immobilized on a gold electrode by multilayer bioengineering based on a mixed self-assembled monolayer and biotin/avidin system, which allows for a well-controlled immobilization of the bioreceptor within its lipid environment. The odorant detection is electronically performed in a quantitative manner by electrochemical impedance spectroscopy (EIS) measurements on samples and controls.

Quantitative assessment of olfactory receptors activity in immobilized nanosomes: a novel concept for bioelectronic nose.

We describe how mammalian olfactory receptors (ORs) could be used as sensing elements of highly specific and sensitive bioelectronic noses. An OR and an appropriate G(alpha) protein were co-expressed in Saccharomyces cerevisiae cells from which membrane nanosomes were prepared, and immobilized on a sensor chip. By Surface Plasmon Resonance, we were able to quantitatively evaluate OR stimulation by an odorant, and G protein activation.

Immobilization of rhodopsin on a self-assembled multilayer and its specific detection by electrochemical impedance spectroscopy.

Rhodopsin, the G protein-coupled receptor (GPCR) which mediates the sense of vision, was prepared from calf eyes and used as receptor enriched membrane fraction. In this study it was immobilized onto gold electrode by two different techniques: Langmuir-Blodgett (LB) and a strategy based on a self-assembled multilayer. We demonstrated that Langmuir and LB films of rhodopsin are not stable.

Immobilization of native membrane-bound rhodopsin on biosensor surfaces.

In this paper, we evaluated the grafting of G-protein-coupled receptors (GPCRs) onto functionalized surfaces, which is a primary requirement to elaborate receptor-based biosensors, or to develop novel GPCR assays. Bovine rhodopsin, a prototypical GPCR, was used in the form of receptor-enriched membrane fraction. Quantitative immobilization of the membrane-bound rhodopsin either non-specifically on a carboxylated dextran surface grafted with long alkyl groups, or specifically on a surface coated with anti-rhodopsin antibody was demonstrated by surface plasmon resonance.

Functional expression of olfactory receptors in yeast and development of a bioassay for odorant screening.

The functional expression of olfactory receptors (ORs) is a primary requirement to examine the molecular mechanisms of odorant perception and coding. Functional expression of the rat I7 OR and its trafficking to the plasma membrane was achieved under optimized experimental conditions in the budding yeast Saccharomyces cerevisiae. The membrane expression of the receptor was shown by Western blotting and immunolocalization methods.

Ligand-specific dose-response of heterologously expressed olfactory receptors.

Primary olfactory neuronal cultures exposed to odorant stimulation have previously exhibited concentration-related effects in terms of intracellular cAMP levels and adenylate cyclase activity [Ronnett, G.V., Parfitt, D.

Localization of orexins and their receptors in the rat olfactory system: possible modulation of olfactory perception by a neuropeptide synthetized centrally or locally.

Orexin-A and -B, also known as hypocretins, are two neuropeptides acting on feeding and sleep. They are specific ligands for two different receptors belonging to the G-protein coupled receptors family. Orexin fibers and orexin receptor neurons have been previously described in the forebrain olfactory system.

Targeted expression of the only zinc finger gene in transgenic mice is associated with impaired mammary development.

The only zinc finger (OZF) gene encodes a protein consisting mainly of 10 zinc finger motifs of the Krüppel type of yet unknown function. To potentially assess its in vivo role, mammary targeted deregulation of the expression of the murine gene was performed in transgenic mice using a goat beta-casein-based transgene. Mammary expression of the transgene was observed in the 11 lines obtained.