Reassembling a system from the sensor to cerebral representation: the olfactory system in vitro.

An odorant's code is represented by activity in a dispersed ensemble of olfactory sensory neurons in the nose, activation of a specific combination of groups of mitral cells in the olfactory bulb and is considered to be mapped at divergent locations in the olfactory cortex. We present here an in vitro model of the mammalian olfactory system developed to gain easy access to all stations of the olfactory pathway. Mouse olfactory epithelial explants are cocultured with a brain slice that includes the olfactory bulb and olfactory cortex areas and maintains the central olfactory pathway intact and functional. Organotypicity of bulb and cortex is preserved and mitral cell axons can be traced to their target areas. Calcium imaging shows propagation of mitral cell activity to the piriform cortex. Long term coculturing with postnatal olfactory epithelial explants restores the peripheral olfactory pathway. Olfactory receptor neurons renew and progressively acquire a mature phenotype. Axons of olfactory receptor neurons grow out of the explant and rewire into the olfactory bulb. The extent of reinnervation exhibits features of a postlesion recovery. Functional imaging confirms the recovery of part of the peripheral olfactory pathway and shows that activity elicited in olfactory receptor neurons or the olfactory nerves is synaptically propagated into olfactory cortex areas. This model is the first attempt to reassemble a sensory system in culture, from the peripheral sensor to the site of cortical representation. It will increase our knowledge on how neuronal circuits in the central olfactory areas integrate sensory input and counterbalance damage.

Effects of anticancer drug docetaxel on the structure and function of the rabbit olfactory mucosa

Docetaxel (DCT) is an anticancer drug which acts by disrupting microtubule dynamics in the highly mitotic cancer cells. Thus, this drug has a potential to affect function and organization of tissues exhibiting high cellular turnover. We investigated, in the rabbit, the effects of a single human equivalent dose (6.26mg/kg, i.v.) of DCT on the olfactory mucosa (OM) through light and electron microscopy, morphometry, Ki-67 immunostaining, TUNEL assay and the buried food test for olfactory sensitivity. On post-exposure days (PED) 5 and 10, there was disarrangement of the normal cell layering in the olfactory epithelium (OE), apoptotic death of cells of the OE, Bowman's glands and axon bundles, and the presence (including on PED 3) of blood vessels in the bundle cores. A decrease in bundle diameters, olfactory cell densities and cilia numbers, which was most significant on PED 10 (49.3%, 63.4% and 50%, respectively), was also evident. Surprisingly by PED 15, the OM regained normal morphology. Furthermore, olfactory sensitivity decreased progressively until PED 10 when olfaction was markedly impaired, and with recovery from the impairment by PED 15. These observations show that DCT transiently alters the structure and function of the OM suggesting a high regenerative potential for this tissue.

Olfactory function after transsphenoidal pituitary surgery

Pituitary surgery remains mainly performed trough a transnasal, transseptal and transsphenoidal way. This surgical approach can damage intranasal structures and, in particular, may impede olfactory function. Our study investigates olfactory function in 67 patients undergoing this type of surgery before and 3 months after surgery. Mean olfactory scores were identical pre- and postoperatively. However, on an individual bases seven percent of the patients showed a clear decrease in olfactory function. In conclusion, transnasal, transseptal and transsphenoidal surgery is relativelv safe with regards to olfactory function

Rivalry of homeostatic and sensory-evoked emotions: dehydration attenuates olfactory disgust and its neural correlates

Neural correlates have been described for emotions evoked by states of homeostatic imbalance (e.g. thirst, hunger, and breathlessness) and for emotions induced by external sensory stimulation (such as fear and disgust). However, the neurobiological mechanisms of their interaction, when they are experienced simultaneously, are still unknown. We investigated the interaction on the neurobiological and the perceptional level using subjective ratings, serum parameters, and functional magnetic resonance imaging (fMRI) in a situation of emotional rivalry, when both a homeostatic and a sensory-evoked emotion were experienced at the same time. Twenty highly dehydrated male subjects rated a disgusting odor as significantly less repulsive when they were thirsty. On the neurobiological level, we found that this reduction in subjective disgust during thirst was accompanied by a significantly reduced neural activity in the insular cortex, a brain area known to be considerably involved in processing of disgust. Furthermore, during the experience of disgust in the satiated condition, we observed a significant functional connectivity between brain areas responding to the disgusting odor, which was absent during the stimulation in the thirsty condition. These results suggest interference of conflicting emotions: An acute homeostatic imbalance can attenuate the experience of another emotion evoked by the sensory perception of a potentially harmful external agent. This finding offers novel insights with regard to the behavioral relevance of biologically different types of emotions, indicating that some types of emotions are more imperative for behavior than others. As a general principle, this modulatory effect during the conflict of homeostatic and sensory-evoked emotions may function to safeguard survival.

Olfactory bulb volume predicts therapeutic outcome in major depression disorder

The volume of the olfactory bulb (OB) is strongly reduced in patients with major depressive disorder (MDD) and this group exhibits markedly decreased olfactory function. It has been suggested that olfactory input is important for maintaining balance in limbic neurocircuits. The aim of our study was to investigate whether reduced OB volume is associated with response to therapy in MDD. Twenty-four inpatients (all women, age 21-49 years, mean 38 ± 10 years SD) with MDD and 36 healthy controls (all women, age 20-52 years, mean 36 ± 10 years SD) underwent structural MRI. OB volume was compared between responders (N = 13) and non-responders (N = 11) to psychotherapy. Retest of OB volume was performed about 6 months after the end of therapy in nine of the patients. Therapy responders exhibited no significant difference in OB volume compared to healthy controls. However, average OB volume of non-responders was 23 % smaller compared to responders (p = .0011). Furthermore, OB volume was correlated with the change of depression severity (r = .46, p = .024). Volume of the OB did not change in the course of therapy. OB volume may be a biological vulnerability factor for the occurrence and/or maintenance of depression, at least in women.

Changes of olfactory abilities in relation to age: odor identification in more than 1400 people aged 4 to 80 years

The currently presented large dataset (n = 1,422) consists of results that have been assembled over the last 8 years at science fairs using the 16-item odor identification part of the "Sniffin' Sticks". In this context, the focus was on olfactory function in children; in addition before testing, we asked participants to rate their olfactory abilities and the patency of the nasal airways. We reinvestigated some simple questions, e.g., differences in olfactory odor identification abilities in relation to age, sex, self-ratings of olfactory function and nasal patency. Three major results evolved: first, consistent with previously published reports, we found that identification scores of the youngest and the oldest participants were lower than the scores obtained by people aged 20-60. Second, we observed an age-related increase in the olfactory abilities of children. Moreover, the self-assessed olfactory abilities were related to actual performance in the smell test, but only in adults, and self-assessed nasal patency was not related to the "Sniffin' Sticks" identification score.

Long lasting phantosmia treated with venlafaxine

Qualitative olfactory disorders such as parosmia and phantosmia are not well investigated. In particular, the causes and treatment options for phantosmia are largely unknown. We report a case of long lasting phantosmia that disappeared under anti-depressive treatment, raising the question to what extent certain forms of qualitative olfactory disorders are an early symptom of depression.

Outer skull landmark-based coordinates for measurement of cerebral blood flow and intracranial pressure in rabbits

Despite the increased use of intracranial neuromonitoring during experimental subarachnoid hemorrhage (SAH), coordinates for probe placement in rabbits are lacking. This study evaluates the safety and reliability of using outer skull landmarks to identify locations for placement of cerebral blood flow (CBF) and intraparenchymal intracranial pressure (ICP) probes. Experimental SAH was performed in 17 rabbits using an extracranial-intracranial shunt model. ICP probes were placed in the frontal lobe and compared to measurements recorded from the olfactory bulb. CBF probes were placed in various locations in the frontal cortex anterior to the coronary suture. Insertion depth, relation to the ventricular system, and ideal placement location were determined by post-mortem examination. ICP recordings at the time of SAH from the frontal lobe did not differ significantly from those obtained from the right olfactory bulb. Ideal coordinates for intraparenchymal CBF probes in the left and right frontal lobe were found to be located 4.6±0.9 and 4.5±1.2 anterior to the bregma, 4.7±0.7mm and 4.7±0.5mm parasagittal, and at depths of 4±0.5mm and 3.9±0.5mm, respectively. The results demonstrate that the presented coordinates based on skull landmarks allow reliable placement of intraparenchymal ICP and CBF probes in rabbit brains without the use of a stereotactic frame.

Alopecia areata in Eringer cows

Alopecia areata is a hair loss disorder in humans, dogs and horses with a suspected autoimmune aetiology targeting anagen hair follicles. Alopecia areata is only sporadically reported in cows. Recently, we observed several cases of suspected alopecia areata in Eringer cows. The aim of this study was to confirm the presumptive diagnosis of alopecia areata and to define the clinical phenotype and histopathological patterns, including characterization of the infiltrating inflammatory cells. Twenty Eringer cows with alopecia and 11 Eringer cows without skin problems were included in this study. Affected cows had either generalized or multifocal alopecia or hypotrichosis. The tail, forehead and distal extremities were usually spared. Punch biopsies were obtained from the centre and margin of alopecic lesions and normal haired skin. Histological examination revealed several alterations in anagen hair bulbs. These included peri- and intrabulbar lymphocytic infiltration, peribulbar fibrosis, degenerate matrix cells with clumped melanosomes and pigmentary incontinence. Mild lymphocytic infiltrative mural folliculitis was seen in the inferior segment and isthmus of the hair follicles. Hair shafts were often unpigmented and dysplastic. The large majority of infiltrating lymphocytes were CD3(+) T cells, whereas only occasional CD20(+) lymphocytes were present in the peribulbar infiltrate. Our findings confirm the diagnosis of T-cell-mediated alopecia areata in these cows. Alopecia areata appears to occur with increased frequency in the Eringer breed, but distinct predisposing factors could not be identified.

Evaluation of smell and taste in patients with Wegener's granulomatosis

Although a reduced olfactory/gustatory function affects patients in all parts of life, this problem has not received much attention in Wegener's granulomatosis (WG). The aim of this study was to assess the smell/taste function of WG patients. Demographic data of 16 WG patients (9 males, 7 females) were obtained. They all subjectively assessed their taste/smell function on visual analogue scale. Olfactory/gustatory functions of the patients were tested with 'Sniffin' Sticks and 'Taste' strips, respectively. The results were then compared with those from sex and age-matched control group (n = 16) and normative data. WG patients subjectively assessed their olfactory (p = 0.03) and gustatory (p = 0.02) function to be lower than control group. All the olfactory scores (odour identification, odour discrimination and threshold) in both genders were significantly below the scores in the control group. WG patients were hyposmic. For taste (total taste score, as well as scores for the qualities sweet, sour, salty and bitter), WG patients did not significantly differ from controls and were normogeusic. However, the gustatory scores showed the tendency of reduction as compared to the control group. In conclusion, WG patients truly suffer from olfactory/taste dysfunction, but this is worse with olfaction. It is, therefore, imperative that physicians should make their patients to be aware of these sensory dysfunctions and educate them on methods to cope with it for better quality of life.

The efficacy of non-pharmacological interventions in the management of procedural pain in preterm and term neonates. A systematic literature review

BACKGROUND: Neonates in a neonatal intensive care unit are exposed to a high number of painful procedures. Since repeated and sustained pain can have consequences for the neurological and behaviour-oriented development of the newborn, the greatest attention needs to be paid to systematic pain management in neonatology. Non-pharmacological treatment methods are being increasingly discussed with regard to pain prevention and relief either alone or in combination with pharmacological treatment. AIMS: To identify effective non-pharmacological interventions with regard to procedural pain in neonates. METHODS: A literature search was conducted via the MedLine, CINAHL, Cochrane Library databases and complemented by a handsearch. The literature search covered the period from 1984 to 2004. Data were extracted according to pre-defined criteria by two independent reviewers and methodological quality was assessed. RESULTS: 13 randomised controlled studies and two meta-analyses were taken into consideration with regard to the question of current nursing practice of non-pharmacological pain management methods. The selected interventions were "non-nutritive sucking", "music", "swaddling", "positioning", "olfactory and multisensorial stimulation", "kangaroo care" and "maternal touch". There is evidence that the methods of "non-nutritive sucking", "swaddling" and "facilitated tucking" do have a pain-alleviating effect on neonates. CONCLUSIONS: Some of the non-pharmacological interventions have an evident favourable effect on pulse rate, respiration and oxygen saturation, on the reduction of motor activity, and on the excitation states after invasive measures. However, unambiguous evidence of this still remains to be presented. Further research should emphasise the use of validated pain assessment instruments for the evaluation of the pain-alleviating effect of non-pharmacological interventions.

Floral scents affect the distribution of hive bees around dancers

Floral scents are important information cues used to organize foraging-related tasks in honeybees. The waggle dance, apart from encoding spatial information about food sources, might facilitate the transfer of olfactory information by increasing the dissipation of volatiles brought back by successful foragers. By assuming that food scents are more intensive on specific body parts of returning foragers, i.e., the posterior legs of pollen foragers and mouthparts of nectar foragers, we quantified the interactions between hive mates and foragers during dances advertising different types of food sources. For natural sources, a higher proportion of hive mates contacted the hind legs of pollen dancers (where the pollen loads were located) with their heads compared to non-pollen dancers. On the other hand, the proportion of head-to-head contacts was higher for non-pollen foragers during the waggle runs. When the food scent was manipulated, dancers collecting scented sugar solution had a higher proportion of head-to-head contacts and a lower proportion around their hind legs compared to dancers collecting unscented solution. The presence of food odors did not affect in-hive behaviors of dancers, but it increased the number of trophallaxes in-between waggle runs (i.e., during circle phases). These results suggest that the honeybee dance facilitates the olfactory information transfer between incoming foragers and hive mates, and we propose that excitatory displays in other social insect species serve the same purpose. While recent empirical and theoretical findings suggested that the colony level foraging benefits of the spatial information encoded in the waggle dance vary seasonally and with habitats, the role of the dance as a compound signal not only indicating the presence of a profitable resource but also amplifying the information transfer regarding floral odors may be important under any ecological circumstances.

GPR87 is an overexpressed G-protein coupled receptor in squamous cell carcinoma of the lung

Lung cancer is the leading cause of cancer death worldwide. The overall 5-year survival after therapy is about 16% and there is a clear need for better treatment options, such as therapies targeting specific molecular structures. G-protein coupled receptors (GPCRs), as the largest family of cell surface receptors, represent an important group of potential targets for diagnostics and therapy. We therefore used laser capture microdissection and GPCR-focused Affymetrix microarrays to examine the expression of 929 GPCR transcripts in tissue samples of 10 patients with squamous cell carcinoma and 7 with adenocarcinoma in order to identify novel targets in non-small cell lung carcinoma (NSCLC). The relative gene expression levels were calculated in tumour samples compared to samples of the neighbouring alveolar tissue in every patient. Based on this unique study design, we identified 5 significantly overexpressed GPCRs in squamous cell carcinoma, in the following decreasing order of expression: GPR87 > CMKOR1 > FZD10 > LGR4 > P2RY11. All are non-olfactory and GRAFS (glutamate, rhodopsin, adhesion, frizzled/taste2, secretin family) classified. GPR87, LGR4 and CMKOR1 are orphan receptors. GPR87 stands out as a candidate for further target validation due to its marked overexpression and correlation on a mutation-based level to squamous cell carcinoma.

Localization of DJ-1 mRNA in the mouse brain

DJ-1 is mutated in autosomal recessive, early onset Parkinson's disease but the exact localization of the DJ-1 gene product in the mammalian brain is largely unknown. We aimed to evaluate the DJ-1 mRNA expression pattern in the mouse brain. Serial coronal sections of brains of five male and five female adult mice were investigated by using in situ hybridization with a DJ-1 specific 35S-labeled oligonucleotide probe. Hybridized sections were analyzed after exposure to autoradiography films and after coating with a photographic emulsion. DJ-1 was heterogeneously expressed throughout the mouse central nervous system. A high expression of DJ-1 mRNA was detected in neuronal and non-neuronal populations of several structures of the motor system such as the substantia nigra, the red nucleus, the caudate putamen, the globus pallidus, and the deep nuclei of the cerebellum. Furthermore, DJ-1 mRNA was also highly expressed in non-motor structures including the hippocampus, the olfactory bulb, the reticular nucleus of the thalamus, and the piriform cortex. The high expression of DJ-1 mRNA in brain regions involved in motor control is compatible with the occurrence of parkinsonian symptoms after DJ-1 mutations. However, expression in other regions indicates that a dysfunction of DJ-1 may contribute to additional clinical features in patients with a DJ-1 mutation.