Long-Lasting Metabolic Imbalance Related to Obesity Alters Olfactory Tissue Homeostasis and Impairs Olfactory-Driven Behaviors.

Obesity is associated with chronic food intake disorders and binge eating. Food intake relies on the interaction between homeostatic regulation and hedonic signals among which, olfaction is a major sensory determinant. However, its potential modulation at the peripheral level by a chronic energy imbalance associated to obese status remains a matter of debate.

Rat strains with different metabolic statuses differ in food olfactory-driven behavior.

In most species, food intake is influenced by olfactory cues and metabolic status can affect the olfactory function of animals and regulate feeding-related behaviors. We investigated whether modulation of the endocrine system that regulates or modifies energy balance affected the olfactory system by examining four rat strains, obese Zucker and obesity-resistant Lou/C rats and their counterparts. Such models were chosen because they differ largely in their energy status and in their insulin and leptin blood levels, two hormones known to impact olfactory behaviors.

Promotion of cancer cell invasiveness and metastasis emergence caused by olfactory receptor stimulation.

Olfactory receptors (ORs) are expressed in the olfactory epithelium, where they detect odorants, but also in other tissues with additional functions. Some ORs are even overexpressed in tumor cells. In this study, we identified ORs expressed in enterochromaffin tumor cells by RT-PCR, showing that single cells can co-express several ORs.

Neuropeptide Y enhances olfactory mucosa responses to odorant in hungry rats.

Neuropeptide Y (NPY) plays an important role in regulating appetite and hunger in vertebrates. In the hypothalamus, NPY stimulates food intake under the control of the nutritional status. Previous studies have shown the presence of NPY and receptors in rodent olfactory system, and suggested a neuroproliferative role.

Chronic restricted access to food leading to undernutrition affects rat neuroendocrine status and olfactory-driven behaviors.

Previous studies have demonstrated that olfactory-driven behaviors in rats are influenced by short-term caloric restriction, partly through the modulation of olfactory sensitivity by appetite-modulating hormones or peptides such as insulin and leptin. Here, we addressed the issue of a long-term modulation of their neuroendocrine status by evaluating the effect of chronic food restriction in rats following a limitation of the duration of daily food intake to 2 h (SF) instead of 8 h (LF) on the expression of insulin and leptin system in the olfactory mucosa and bulb and on olfactory behaviors. This restriction resulted in a one-third reduction in the daily food intake and a 25% reduction in the body weight of SF rats when compared to controls, and was accompanied by lower levels of triglycerides, glucose, insulin and leptin in SF rats.

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.

Insulin but not leptin protects olfactory mucosa from apoptosis.

The mammalian olfactory mucosa (OM) is continually renewed throughout life. Owing to their position in the nasal cavity, OM cells are exposed to multiple insults, including high levels of odourants that can induce their death. OM regeneration is therefore essential to maintain olfactory function, and requires the tight control of both cell death and proliferation.

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.

Leptin-sensitive OBP-expressing mucous cells in rat olfactory epithelium: a novel target for olfaction-nutrition crosstalk?

Although odorant-binding proteins (OBP) are one of the most abundant classes of proteins in the mammalian olfactory mucus, they have only recently been ascribed a functional role in the detection of odorants by olfactory neurons. Among the three OBPs described in the rat, OBP-1f is mainly secreted by the lateral nasal glands (LNG) and Bowman's glands, and its expression is transcriptionally regulated by food deprivation in the olfactory mucosa, but not in LNG. Therefore, mucus composition might be locally regulated by hormones or molecules relevant to nutritional status.

Expression of insulin system in the olfactory epithelium: first approaches to its role and regulation.

Food odours are major determinants for food choice; their detection is influenced by nutritional status. Among different metabolic signals, insulin plays a major role in food intake regulation. The aim of the present study was to investigate a potential role of insulin in the olfactory mucosa (OM), using ex vivo tissues and in vitro primary cultures.

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.

Transcription profile analysis reveals that OBP-1F mRNA is downregulated in the olfactory mucosa following food deprivation.

Neuroanatomical data show that olfactory mucosa (OM) is a possible place for interactions between nutrition and smell. A combination of differential display mRNA analysis together with a macroarray screening was developed to identify transcripts that are differentially expressed in rat OM following food deprivation. Using this method, backed on a stringent statistical analysis, we identified molecules that fell into several Gene Ontology terms including cellular and physiological process, signal transduction, and binding.

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.

Uterine motor alterations and estrous cycle disturbances associated with colonic inflammation in the rat.

The impact of colitis on uterine contractility and estrous cycle was investigated after intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. Colitis severity was assessed by macroscopic damage scoring (MDS) 4 days after TNBS, and myeloperoxidase (MPO) activity was measured in both colon and uterus of control and colitic rats. Estrous cycle stages were determined by vaginal smears and histology, and uterine contractility was assessed in vitro on longitudinal and circular strips.

Spinal control of erection by glutamate in rats.

The lumbosacral spinal network controlling penile erection is activated by information from peripheral and supraspinal origins. We tested the hypothesis that glutamate, released by sensory afferents from the genitals, activates this proerectile network. In anesthetized intact and T8 spinalized (i.

Plasma levels of cortisol and oxytocin, and uterine activity after cervical artificial insemination in the ewe.

The objective was to compare in the ewe the effects of easy and difficult procedures for artificial insemination (AI) (as related to rapid or poor accessibility of the cervix, respectively) on plasma cortisol (CORT) and oxytocin (OT), and uterine motility. All AI were simulated using a catheter empty of semen to study genital and environmental stimuli only. In experiment 1, 40 ewes were sampled after Al, and whether it was an easy or difficult procedure was reported for each animal.

Distribution of arginine-vasopressin and vasoactive intestinal peptide messenger RNA in the suprachiasmatic nucleus of the sheep.

The distribution of mRNAs for vasoactive intestinal peptide (VIP) and arginine-vasopressin (VP) was studied in the hypothalamus of the sheep by in situ hybridization. VIP mRNA was detected in the supraoptic nucleus (SON) and in the median part of the suprachiasmatic nucleus (SCN). VP mRNA was observed in the magnocellular system of the hypothalamus and in the dorso-lateral part of the SCN.

Vasoactive intestinal polypeptide in the suprachiasmatic nucleus of the mink (Mustela vison) could play a key role in photic induction.

The present study was conducted to visualize neuropeptides in the SCN of a mustelid, the American mink in which seasonal cycles of reproduction rely totally on the annual changes in day length. At this time, data in mustelids are lacking. Results were obtained with in situ hybridization (ISH) using synthetic oligonucleotide vasopressin (AVP) and somatostatin (SOM) and with single and dual immunohistochemistry (IHC) performed with antisera against AVP, SOM, vasoactive intestinal polypeptide (VIP), gastrin releasing peptide (GRP) and met-enkephalin (Met-ENK) in untreated (AVP and VIP) or colchicine (SOM, Met-ENK and GRP) treated adult male and female mink.

Melatonin and the circadian clock in mink: effects of daily injections of melatonin on circadian rhythm of locomotor activity and autoradiographic localization of melatonin binding sites.

The present study examines a putative effect of exogenous melatonin on the circadian organization of the mink. Two approaches were used to determine first whether entrainment of free-running rhythms of locomotor activity in constant darkness can be obtained by daily melatonin injections, thus demonstrating a control of melatonin on the clock generating circadian rhythms, the suprachiasmatic nucleus of the hypothalamus. Entrainment was never obtained in the 8 vehicle-injected females and 7 out of the 8 melatonin injected-ones.

Endogenous circannual rhythms and photorefractoriness of testis activity, moult and prolactin concentrations in mink (Mustela vison).

Mink are seasonal photosensitive breeders; testis activity is triggered when days have less than 10 h light. Increasing and decreasing plasma concentrations of prolactin induce the spring and autumn moults. In a 5 year experiment, males were maintained under short days (8 h light:16 h dark) at 13 degrees C or long days (16 h light:8 h dark) at 21 degrees C, winter and summer conditions, respectively.

Effects of Timed Melatonin Infusions and Lesions of the Suprachiasmatic Nuclei on Prolactin and Progesterone Secretions in Pregnant or Pseudopregnant Mink (Mustela vison).

Abstract To test the hypothesis that the duration of melatonin secretion may be a critical parameter in the transduction of photoperiodic signals on prolactin and progesterone secretions, timed intravenous melatonin infusions were carried out in intact and ganglionectomized pregnant and pseudopregnant mink. To localize the target sites of melatonin, electrolytic lesions of hypothalamic nuclei were performed in females receiving melatonin infusions. As a control, the first experiment was designed to confirm that pineal denervation by bilateral ablation of the superior cervical ganglion rendered the pregnant mink totally unresponsive to the inhibitory effects of short days on progesterone secretion.