RESUMO
The OR37 subfamily of odorant receptors(ORs) exists exclusively in mammals. In contrast to ORs in general, they are highly conserved within and across species.These unique features raise the question, whether olfactory information gathered by the OR37 sensory cells is processed in specially designated brain areas. To elucidate the wiring of projection neurons from OR37 glomeruli into higher brain areas, tracing experiments were performed.The application of DiI onto the ventral area of the olfactory bulb, which harbors the OR37 glomeruli, led to the labeling of fibers not only in the typical olfactory cortical regions,but also in the medial amygdala and the hypothalamus. To visualize the projections from a defined OR37 glomerulus more precisely, transgenic mice were studied in which olfactory sensory neurons co-express the receptor subtype OR37C and the transsynaptic tracer wheat germ agglutinin(WGA). WGA became visible not only in the OR37C sensory neurons and the corresponding OR37C glomerulus,but also in cell somata located in the mitral/tufted cell layer adjacent to the OR37C glomerulus, indicating a transfer of WGA onto projection neurons. In the brain, WGA immunoreactivity was not detectable in typical olfactory cortical areas, but instead in distinct areas of the medial amygdala.Detailed mapping revealed that the WGA immunoreactivity was restricted to the posterior-dorsal subnucleus of the medial amygdala. In addition, WGA immunoreactivity was visible in some well-circumscribed areas of the hypothalamus.These results are indicative for a unique connectivity from OR37C sensory cells into higher brain centers.
Assuntos
Encéfalo/metabolismo , Neurônios Receptores Olfatórios/metabolismo , Receptores Odorantes/genética , Aglutininas do Germe de Trigo/análise , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores Odorantes/biossínteseRESUMO
Olfactory sensory neurons (OSNs) which express distinct odorant receptor (OR) genes are spatially arranged within the mouse olfactory epithelium. Towards an understanding of the mechanisms which determine these patterns, representative OR genes which are typically expressed in the unique central patch of the epithelium were investigated. Inside the patch, numerous OSNs which initially selected a representative gene from this OR group finally expressed another gene from the group, indicating that OSNs inside the patch 'switch' between these genes. If an OSN successively chose genes from the same OR gene cluster, these originated from the same parental chromosome. A deletion of the olfactory cyclic nucleotide-gated ion channel altered the distribution pattern of distinct OSN populations; they were no longer located exclusively inside the patch. Together, the results indicate that OSNs inside the patch initially sample several OR genes for expression; for their correct patterning in the OE, odor-induced activity appears to play a critical role.
Assuntos
Regulação da Expressão Gênica , Odorantes , Neurônios Receptores Olfatórios/fisiologia , Isoformas de Proteínas/genética , Receptores Odorantes/genética , Olfato/fisiologia , Animais , Feminino , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Família Multigênica , Bulbo Olfatório/citologia , Mucosa Olfatória/citologia , Mucosa Olfatória/metabolismo , Neurônios Receptores Olfatórios/citologia , Isoformas de Proteínas/metabolismo , Receptores Odorantes/metabolismoRESUMO
Olfactory sensory neurons (OSNs) expressing the same odorant receptor (OR) gene are generally widely dispersed throughout the olfactory epithelium (OE). In contrast, OSNs expressing any member from the special OR37 subfamily are concentrated in a small patch in the centre of the OE. To evaluate whether transcription of OR37 genes is only possible in the patch region, or if they can generally be chosen also in non-appropriate areas, a transgenic approach was employed that permanently labelled all cells which ever transcribed a representative OR37 gene. It was found that - in addition to cells inside the patch - numerous cells outside were labelled, indicating that they had transcribed the OR37 gene, but then turned it off while choosing another OR gene. Permanent expression of the OR37 gene was exclusively maintained in the patch. The results suggest that mechanisms acting downstream of an initial OR gene choice restrict OR37 expression to the patch.
Assuntos
Regulação da Expressão Gênica , Bulbo Olfatório/metabolismo , Receptores Odorantes/metabolismo , Órgão Vomeronasal/metabolismo , Animais , Proteínas de Bactérias/genética , Integrases/genética , Integrases/metabolismo , Proteínas Luminescentes/genética , Camundongos , Camundongos Transgênicos , RNA Mensageiro/metabolismo , Receptores Odorantes/genéticaRESUMO
BACKGROUND: Non-communicable diseases (NCDs) are increasing worldwide. A lack of training and experience in NCDs among public health workers is evident in low- and middle- income countries. METHODS: We describe the design and outcomes of applied training in NCD epidemiology and control piloted in Tanzania that included a 2-week interactive course and a 6-month NCD field project. Trainees (n=14 initiated; n=13 completed) were epidemiology-trained Ministry of Health or hospital staff. We evaluated the training using Kirkpatrick's evaluation model for measuring reactions, learning, behavior and results using pre- and post-tests and closed-ended and open-ended questions. RESULTS: Significant improvements in knowledge and self-reported competencies were observed. Trainees reported applying competencies at work and supervisors reported improvements in trainees' performance. Six field projects were completed; one led to staffing changes and education materials for patients with diabetes and another to the initiation of an injury surveillance system. Workplace support and mentoring were factors that facilitated the completion of projects. Follow-up of participants was difficult, limiting our evaluation of the training's outcomes. CONCLUSIONS: The applied NCD epidemiology and control training piloted in Tanzania was well received and showed improvements in knowledge, skill and self-efficacy and changes in workplace behavior and institutional and organizational changes. Further evaluations are needed to better understand the impact of similar NCD trainings and future trainers should ensure that trainees have mentoring and workplace support prior to participating in an applied NCD training.
Assuntos
Doença Crônica/epidemiologia , Atenção à Saúde/organização & administração , Países em Desenvolvimento , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/educação , Competência Clínica , Atenção à Saúde/normas , Diabetes Mellitus/epidemiologia , Humanos , Educação de Pacientes como Assunto , Saúde Pública , Tanzânia , Ferimentos e Lesões/epidemiologiaRESUMO
Olfactory sensory neurons (OSNs) which express a member from the OR37 subfamily of odorant receptor (OR) genes are wired to the main olfactory bulb (MOB) in a unique monoglomerular fashion; from these glomeruli an untypical connectivity into higher brain centers exists. In the present study we have investigated by DiI and transsynaptic tracing approaches how the connection pattern from these glomeruli into distinct hypothalamic nuclei is organized. The application of DiI onto the ventral domain of the bulb which harbors the OR37 glomeruli resulted in the labeling of fibers within the paraventricular nucleus (PVN) and supraoptic nucleus (SO) of the hypothalamus; some of these fibers were covered with varicose-like structures. No DiI-labeled cell somata were detectable in these nuclei. The data indicate that projection neurons which originate in the OR37 region of the MOB form direct connections into these nuclei. The cells that were labeled by the transsynaptic tracer WGA in these nuclei were further characterized. Their distribution pattern in the paraventricular nucleus was reminiscent of cells which produce distinct neuropeptides. Double labeling experiments confirmed that they contained vasopressin, but not the related neuropeptide oxytocin. Morphological analysis revealed that they comprise of magno- and parvocellular cells. A comparative investigation of the WGA-positive cells in the SO demonstrated that these were vasopressin-positive, as well, whereas oxytocin-producing cells of this nucleus also contained no transsynaptic tracer. Together, the data demonstrates a connectivity from OR37 expressing sensory neurons to distinct hypothalamic neurons with the same neuropeptide content.