RESUMO
The olfactory and vomeronasal systems of vertebrates are characterised by neurogenesis occurring throughout life. The regenerative ability of olfactory receptor neurons relies on specific glial cells, the olfactory and vomeronasal axon-surrounding cells. Numerous studies have examined mammalian olfactory ensheathing cells which are considered potential candidates for spinal cord injury repair using cell-based therapy. With regard to non-mammalian vertebrates, limited information is available on these glial cells in fish, and there is no information on them in terrestrial anamniotes, the amphibians. In the present research, we studied the immunocytochemical characteristics of axon-surrounding cells in Ambystoma mexicanum. Urodeles have relatively simple olfactory and vomeronasal systems, and represent a good model for studying ensheathing cells in extant representatives of basal tetrapods. Sections from the decalcified heads of A. mexicanum were immunocytochemically processed for the detection of proteins used in research on mammalian olfactory-ensheathing cells. S100, GFAP and NCAM were clearly observed. p75NTR, Gal-1 and PSA-NCAM showed weak staining. No vimentin immunopositivity was observed. The corresponding areas of the olfactory and vomeronasal pathways displayed the same staining characteristics, with the exception of Gal-1, p75NTR and PSA-NCAM in the mucosae. The degree of marker expression was not uniform throughout the sensory pathways. In contrast to fish, both olfactory and vomeronasal nerves displayed uniform staining intensity. This study showed that some markers for mammalian and fish-ensheathing glia are also applicable in urodeles. The olfactory systems of vertebrates show similarities, and also clear dissimilarities. Further investigations are required to ascertain the functional significance of these regional and interspecific differences.
Assuntos
Ambystoma mexicanum/metabolismo , Neuroglia/metabolismo , Animais , Axônios/metabolismo , Condutos Olfatórios/metabolismo , Receptor de Fator de Crescimento Neural/metabolismo , Olfato/fisiologia , Traumatismos da Medula Espinal/metabolismo , Órgão Vomeronasal/fisiologiaRESUMO
Mothers who consume alcohol during pregnancy may cause a neurotoxic syndrome termed fetal alcohol spectrum disorder (FASD) in the offspring, which includes cognitive deficits and emotional/social disturbances. These alterations are thought to be caused, at least in part, by alcohol-induced imbalance in neurotrophic factor levels, which are critically involved in normal neurodevelopment. Our goal was to study whether brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) expression were affected by alcohol in central extended amygdala (CEXA) and pyriform cortex (Pyr), structures strongly involved in emotional/social behaviors. Further, we evaluated how these changes could be related to blood and brain alcohol concentrations. Postnatal day (PND) pups at 7, 15 and 20-days old were administered alcohol (2.5g/kg s.c. at 0 and 2h) or saline. Immunohistochemistry was used to detect the expression of BDNF and GDNF at 2, 12 and 24h after drug administration. Also, gas chromatography was bused to measure blood alcohol levels (BALs) and brain alcohol levels (BrALs) at each hour, from 2 to 8h after the second alcohol administration. Results showed: (1) alcohol-induced enhancement of BDNF positive cells on PND 7 and 20, a decrease on PND 15 in the CEXA, and no changes in the Pyr on PND 7 and 20, but a diminished on PND 15; (2) GDNF positive cells rise after alcohol administration for the three ages in the CEXA and Pyr except on PND 15, where there was a decline; and (3) pharmacokinetics analysis demonstrated age-related differences showing equal BALs on PND 7 and 20 but higher BALs on PND 15. In contrast, BrALs were higher on PND 7 than 15 and 20. Hence, BALs may not be predictive of BrALs in postnatal rats. Furthermore, we did not find a relationship between age in pharmacokinetic differences and neurotrophins response. In conclusion, the CEXA and Pyr are brain structures sensitive to alcohol-induced imbalance in neurotrophic factors expression; and BALs are not a mirror of BrALs.
Assuntos
Envelhecimento/metabolismo , Tonsila do Cerebelo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Etanol/sangue , Etanol/intoxicação , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Condutos Olfatórios/metabolismo , Envelhecimento/efeitos dos fármacos , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Consumo Excessivo de Bebidas Alcoólicas , Masculino , Taxa de Depuração Metabólica , Condutos Olfatórios/efeitos dos fármacos , Ratos , Ratos Wistar , Distribuição TecidualRESUMO
The causes of Parkinson's disease (PD) are unknown, but there is evidence that exposure to environmental agents, including a number of viruses, toxins, agricultural chemicals, dietary nutrients, and metals, is associated with its development in some cases. The presence of smell loss and the pathological involvement of the olfactory pathways in the early stages of PD are in accord with the tenants of the olfactory vector hypothesis. This hypothesis postulates that some forms of PD may be caused or catalyzed by environmental agents that enter the brain via the olfactory mucosa. In this article, we provide an overview of evidence implicating xenobiotics agents in the etiology of PD and review animal, mostly rodent, studies in which toxicants have been introduced into the nose in an attempt to induce behavioral or neurochemical changes similar to those seen in PD. The available data suggest that this route of exposure results in highly variable outcomes, depending upon the involved xenobiotic, exposure history, and the age and species of the animals tested. Some compounds, such as rotenone, paraquat, and 6-hydroxydopamine, have limited capacity to reach and damage the nigrostriatal dopaminergic system via the intranasal route. Others, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), readily enter the brain via this route in some species and influence the function of the nigrostriatal pathway. Intranasal infusion of MPTP in some rodents elicits a developmental sequence of behavioral and neurochemical changes that closely mimics that seen in PD. For this reason, such an MPTP rodent model appears to be an ecologically valid means for assessing novel palliative treatments for both the motor and non-motor symptoms of PD. More research is needed, however, on this and other ecologically valid models.
Assuntos
Neurotoxinas/administração & dosagem , Transtornos Parkinsonianos/etiologia , Administração Intranasal , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Metais/administração & dosagem , Metais/toxicidade , Camundongos , Condutos Olfatórios/metabolismo , Oxidopamina/administração & dosagem , Oxidopamina/toxicidade , Transtornos Parkinsonianos/metabolismo , Praguicidas/toxicidade , Ratos , Vírus/patogenicidadeRESUMO
Decapod crustaceans show proliferation of the nerve cells in the olfactory lobe throughout their lives. However, the regulation of this process is still poorly understood, since it may vary with endogenous and exogenous factors. The objective of the present investigation was to quantify the proliferation of nerve cells and number of nerve cells with ecdysone receptors in the clusters of the central olfactory system in Neohelice granulata, according to moult stages and in different seasons (summer and winter). Three injections of bromodeoxyuridine (BrdU) were administered to the crabs. Brains were sectioned by microtome and fixed on slides for immunohistochemistry with anti-BrdU and anti-EcR antibodies. The proliferation of nerve cells was higher in winter than in summer, probably because in winter the crabs do not breed and the premoult and postmoult periods are longer. Crabs in postmoult exhibited more BrdU-labelled cells than crabs in premoult or intermoult in winter, because of a greater number of mitoses related to an increase in body size and addition of olfactory receptor neurons. The number of EcR-labelled cells was higher in premoult than in postmoult or intermoult in winter. The proliferation of nerve cells is regulated seasonally and according to moult stages.
Assuntos
Braquiúros , Proliferação de Células , Muda/fisiologia , Neurônios/citologia , Receptores de Esteroides/metabolismo , Estações do Ano , Animais , Contagem de Células , Sistema Nervoso Central/citologia , Sistema Nervoso Central/fisiologia , Ecdisona/metabolismo , Ecdisona/fisiologia , Gânglios dos Invertebrados/citologia , Gânglios dos Invertebrados/metabolismo , Neurônios/metabolismo , Condutos Olfatórios/citologia , Condutos Olfatórios/metabolismoRESUMO
Olfactory information modulates innate and social behaviors in rodents and other species. Studies have shown that the medial nucleus of the amygdala (MEA) and the ventral premammillary nucleus (PMV) are recruited by conspecific odor stimulation. However, the chemical identity of these neurons is not determined. We exposed sexually inexperienced male rats to female or male odors and assessed Fos immunoreactivity (Fos-ir) in neurons expressing NADPH diaphorase activity (NADPHd, a nitric oxide synthase), neuropeptide urocortin 3, or glutamic acid decarboxylase mRNA (GAD-67, a GABA-synthesizing enzyme) in the MEA and PMV. Male and female odors elicited Fos-ir in the MEA and PMV neurons, but the number of Fos-immunoreactive neurons was higher following female odor exposure, in both nuclei. We found no difference in odor induced Fos-ir in the MEA and PMV comparing fed and fasted animals. In the MEA, NADPHd neurons colocalized Fos-ir only in response to female odors. In addition, urocortin 3 neurons comprise a distinct population and they do not express Fos-ir after conspecific odor stimulation. We found that 80% of neurons activated by male odors coexpressed GAD-67 mRNA. Following female odor, 50% of Fos neurons coexpressed GAD-67 mRNA. The PMV expresses very little GAD-67, and virtually no colocalization with Fos was observed. We found intense NADPHd activity in PMV neurons, some of which coexpressed Fos-ir after exposure to both odors. The majority of the PMV neurons expressing NADPHd colocalized cocaine- and amphetamine-regulated transcript (CART). Our findings suggest that female and male odors engage distinct neuronal populations in the MEA, thereby inducing contextualized behavioral responses according to olfactory cues. In the PMV, NADPHd/CART neurons respond to male and female odors, suggesting a role in neuroendocrine regulation in response to olfactory cues.
Assuntos
Tonsila do Cerebelo/citologia , Hipotálamo Posterior/citologia , Neurônios/fisiologia , Odorantes , Proteínas Oncogênicas v-fos/metabolismo , Caracteres Sexuais , Animais , Jejum/fisiologia , Feminino , Regulação da Expressão Gênica/fisiologia , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/metabolismo , Hipotálamo Posterior/anormalidades , Masculino , NADPH Desidrogenase/genética , NADPH Desidrogenase/metabolismo , Condutos Olfatórios/metabolismo , RNA Mensageiro/metabolismo , Ratos , Urocortinas/genética , Urocortinas/metabolismoRESUMO
Accumulating evidence points to the mesolimbic and the nigrostriatal dopamine systems as critical to behavioral sensitization induced by several drugs of abuse. In the present study, we analyzed D1 and D2 binding to brain regions related to these dopaminergic systems during the expression of ethanol-induced behavioral sensitization. The first experiment was performed to demonstrate the effectiveness of the ethanol treatment schedule and challenge used to induce the expression of the behavioral sensitization phenomenon. The second experiment was conducted to study D1 and D2 alterations in several brain regions during the expression of this phenomenon. Mice were ip treated with ethanol or saline for 21 consecutive days and 24 h after the last injection they received an ethanol or a saline challenge injection. Five minutes later, the animals were observed in an open-field for locomotion quantification or were sacrificed and their brains were submitted to autoradiographic binding analyses. No differences among the groups were found for D1 binding levels in all the brain regions analyzed. However, ethanol-sensitized mice showed reduced levels of D2 binding in the olfactory tubercle when compared to the other groups. Our data suggest that D2 receptor changes in the olfactory tubercle seem to play an important role in the expression of ethanol-induced behavioral sensitization.
Assuntos
Comportamento Animal/efeitos dos fármacos , Depressores do Sistema Nervoso Central/administração & dosagem , Etanol/administração & dosagem , Condutos Olfatórios/metabolismo , Receptores Dopaminérgicos/metabolismo , Análise de Variância , Animais , Autorradiografia/métodos , Benzazepinas/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Antagonistas de Dopamina/farmacologia , Feminino , Locomoção/efeitos dos fármacos , Camundongos , Condutos Olfatórios/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Racloprida/farmacologia , Receptores Dopaminérgicos/efeitos dos fármacosRESUMO
Olfactory sensory neurons are able to detect odorants with high sensitivity and specificity. We have demonstrated that Ric-8B, a guanine nucleotide exchange factor (GEF), interacts with Galphaolf and enhances odorant receptor signaling. Here we show that Ric-8B also interacts with Ggamma13, a divergent member of the Ggamma subunit family which has been implicated in taste signal transduction, and is abundantly expressed in the cilia of olfactory sensory neurons. We show that Gbeta1 is the predominant Gbeta subunit expressed in the olfactory sensory neurons. Ric-8B and Gbeta1, like Galphaolf and Ggamma13, are enriched in the cilia of olfactory sensory neurons. We also show that Ric-8B interacts with Galphaolf in a nucleotide dependent manner, consistent with the role as a GEF. Our results constitute the first example of a GEF protein that interacts with two different olfactory G protein subunits and further implicate Ric-8B as a regulator of odorant signal transduction.
Assuntos
Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Proteínas Nucleares/metabolismo , Neurônios Receptores Olfatórios/metabolismo , Animais , Linhagem Celular , Cílios/química , Cílios/metabolismo , Subunidades alfa de Proteínas de Ligação ao GTP/análise , Subunidades beta da Proteína de Ligação ao GTP , Fatores de Troca do Nucleotídeo Guanina , Proteínas Heterotriméricas de Ligação ao GTP/análise , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Nucleares/análise , Condutos Olfatórios/química , Condutos Olfatórios/metabolismo , Neurônios Receptores Olfatórios/química , Ligação Proteica/fisiologia , Células Receptoras Sensoriais/química , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais/fisiologiaRESUMO
Through the sense of smell mammals can detect and discriminate between a large variety of odorants present in the surrounding environment. Odorants bind to a large repertoire of odorant receptors located in the cilia of olfactory sensory neurons of the nose. Each olfactory neuron expresses one single type of odorant receptor, and neurons expressing the same type of receptor project their axons to one or a few glomeruli in the olfactory bulb, creating a map of odorant receptor inputs. The information is then passed on to other regions of the brain, leading to odorant perception. To understand how the olfactory system discriminates between odorants, it is necessary to determine the odorant specificities of individual odorant receptors. These studies are complicated by the extremely large size of the odorant receptor family and by the poor functional expression of these receptors in heterologous cells. This article provides an overview of the methods that are currently being used to investigate odorant receptor-ligand interactions.
Assuntos
Receptores Odorantes/metabolismo , Animais , Humanos , Ligantes , Condutos Olfatórios/metabolismo , Transdução de Sinais , Especificidade por SubstratoRESUMO
The long term inhibition of masculine sexual behavior after repeated ejaculations is known as sexual satiety. To investigate the brain areas that may regulate sexual satiety, c-Fos expression was studied in different groups of sexually experienced male rats: controls not allowed to copulate, males allowed two or four ejaculations and animals allowed to reach sexual satiety. Interestingly, males that ejaculated two or four times had similar c-Fos densities in all the evaluated brain regions, except for the suprachiasmatic nucleus. Similarly, sexually satiated males had analogous c-Fos densities in all the evaluated brain areas independently of the number of ejaculations required to reach satiety. Sexual activity (evidenced in males that ejaculated two or four times) increased c-Fos levels in the anteromedial bed nucleus of the stria terminalis, claustrum, entorhinal cortex, medial preoptic area, nucleus accumbens core, suprachiasmatic nucleus and supraoptic nucleus; however, sexual satiety did not modify c-Fos expression in these regions. Sexually satiated males had increased c-Fos densities in the ventrolateral septum and the anterodorsal and posteroventral medial amygdala, compared with animals allowed to copulate but that did not reach sexual satiety, and decreased c-Fos density in the piriform cortex. These results suggest that the network that underlies sexual satiety is different from that which regulates copulation.
Assuntos
Mapeamento Encefálico , Sistema Límbico/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Saciação/fisiologia , Comportamento Sexual Animal/fisiologia , Tonsila do Cerebelo/metabolismo , Animais , Imuno-Histoquímica , Masculino , Condutos Olfatórios/metabolismo , Giro Para-Hipocampal/metabolismo , Prosencéfalo/metabolismo , Ratos , Ratos Wistar , Septo do Cérebro/metabolismoRESUMO
Since protein kinase C (PKC) is known to be activated in the olfactory bulb and in several limbic areas related to odor processing, we determined whether an olfactory stimulus was able to modulate the activity of PKC in animals with bilateral entorhinal cortex lesion. The translocation of PKC from the cytosol to the membrane was studied using the phorbol ester 12,13-dibutyrate ([3H]PDBu) binding in control and bilateral entorhinal cortex (EC) lesioned rats. The lesion of EC per se did not significantly affect [3H]PDBu binding in any of the brain structures analyzed, while odor stimulation induced it in both control and EC-lesioned groups in the external plexiform layer of the olfactory bulb. In contrast, an odor-induced increase of [3H]PDBu binding in internal glomerular layer of the olfactory bulb was only observed in EC lesioned animals. Similar results were obtained in the piriform cortex. In both CA1 and CA3 hippocampal subfields, odor stimulation induced an increase of [3H]PDBu binding in both control and EC-lesioned animals, the increase being potentiated only in CA1 of lesioned rats. The dentate gyrus and the amygdala exhibited a similar pattern of [3H]PDBu binding, showing a significant increase exclusively in EC-lesioned animals after odor stimulation. The results strongly suggest that the EC plays a key role in odor processing. PKC appears to play an important role in responding to the activation of lipid second messengers, which have been described to be involved in the processing of odor stimuli in several structures of the olfactory pathway.