RESUMO
Axonal projection is controlled by discrete regions localized at the neuroepithelium, guiding the neurite growth during embryonic development. These regions exert their effect through the expression of a family of chemotropic molecules, which actively participate in the formation of neuronal connections of the central nervous system in vertebrates. Previous studies describe prosomere 1 (P1) as a possible organizer of axonal growth of the rostral rhombencephalon, contributing to the caudal projection of reticulospinal rhombencephalic neurons. This work studies the contribution of chemotropic signals from P1 or pretectal medial longitudinal fascicle (MLF) neurons upon the caudal projection of the interstitial nuclei of Cajal (INC). By using in ovo surgeries, retrograde axonal labeling, and immunohistochemical techniques, we were able to determine that the absence of P1 generates a failure in the INC caudal projection, while drastically diminishing the reticulospinal rhombencephalic neurons projections. The lack of INC projection significantly decreases the number of reticulospinal neurons projecting to the MLF. We found a 48.6% decrease in the projections to the MLF from the rostral and bulbar areas. Similarly, the observed decrease at prosomere 2 was 51.5%, with 61.8% and 32.4% for prosomeres 3 and 4, respectively; thus, constituting the most affected rostral regions. These results suggest the following possibilities: i, that the axons of the reticulospinal neurons employ the INC projection as a scaffold, fasciculating with this pioneer projection; and ii, that the P1 region, including pretectal MLF neurons, exerts a chemotropic effect upon the INC caudal projection. Nonetheless the identification of these chemotropic signals is still a pending task.
Assuntos
Diencéfalo/crescimento & desenvolvimento , Células Intersticiais de Cajal/fisiologia , Vias Neurais/crescimento & desenvolvimento , Vias Neurais/fisiologia , Animais , Axônios , Embrião de Galinha , Diencéfalo/fisiologia , Imuno-Histoquímica , Neuritos , Neurônios/fisiologia , Rombencéfalo/crescimento & desenvolvimento , Rombencéfalo/fisiologiaRESUMO
Childhood overweight and obesity are worldwide public health problems and risk factors for chronic diseases. The presence of SNP in several genes has been associated with the presence of obesity. A total of 580 children (8-13 years old) from Queretaro, Mexico, participated in this cross-sectional study, which evaluated the associations of rs9939609 (fat mass obesity-associated (FTO)), rs17782313 (melanocortin 4 receptor (MC4R)) and rs6548238 (transmembrane protein 18 (TMEM18)) SNP with obesity and metabolic risk factors. Overweight and obesity prevalence was 19·8 and 19·1 %, respectively. FTO, MC4R and TMEM18 risk allele frequency was 17, 9·8 and 89·5 %, respectively. A significant association between FTO homozygous and MC4R heterozygous risk alleles and obesity was found (OR 3·9; 95 % CI 1·46, 10·22, and OR 2·1; 95 % CI 1·22, 3·71; respectively). The FTO heterozygous subjects showed higher systolic and diastolic blood pressures, compared with the homozygous for the ancestral allele subjects. These results remain significant after considering adiposity as a covariate. The FTO and MC4R genotypes were not significantly associated with total cholesterol, HDL-cholesterol and insulin concentration. No association was found between TMEM18 risk allele and obesity and/or metabolic alterations. Our results show that, in addition to a higher BMI, there is also an association of the risk genotype with blood pressure in the presence of the FTO risk genotype. The possible presence of a risk genotype in obese children must be considered to offer a more comprehensive therapeutic approach in order to delay and/or prevent the development of chronic diseases.
Assuntos
Infecções Bacterianas/epidemiologia , Enterococcus/efeitos dos fármacos , Enterococcus/isolamento & purificação , Resistência a Vancomicina , Infecções Bacterianas/prevenção & controle , Microbiologia Ambiental , Hospitais , Humanos , Controle de Infecções/métodos , México/epidemiologia , Testes de Sensibilidade Microbiana/métodos , PrevalênciaRESUMO
Iodide is a trace element and a key component of thyroid hormones (TH). The availability of this halogen is the rate-limiting step for TH synthesis; therefore, thyroidal iodide uptake and recycling during TH synthesis are of major importance in maintaining an adequate supply. In the rat, the thyroid gland co-expresses a distinctive pair of intrathyroidal deiodinating enzymes: the thyroid iodotyrosine dehalogenase (tDh) and the iodothyronine deiodinase type 1 (ID1). In the present work, we studied the activity of these two dehalogenases in conditions of hypo- and hyperthyroidism as well as during acute and chronic iodide administration in both intact and hypophysectomized (HPX) rats. In order to confirm our observations, we also measured the mRNA levels for both dehalogenases and for the sodium/iodide symporter, the protein responsible for thyroidal iodide uptake. Our results show that triiodothyronine differentially regulates tDh and ID1 enzymatic activities, and that both acute and chronic iodide administration significantly decreases rat tDh and ID1 activities and mRNA levels. Conversely, both enzymatic activities increase when intrathyroidal iodide is pharmacologically depleted in TSH-replaced HPX rats. These results show a regulatory effect by iodide on the intrathyroidal dehalogenating enzymes and suggest that they contribute to the iodide-induced autoregulatory processes involved in the Wolff-Chaikoff effect.
Assuntos
Hidrolases/metabolismo , Iodeto Peroxidase/metabolismo , Iodetos/farmacologia , Glândula Tireoide/metabolismo , Análise de Variância , Animais , Hidrolases/genética , Hipofisectomia , Iodeto Peroxidase/genética , Iodetos/metabolismo , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Simportadores/genética , Simportadores/metabolismo , Glândula Tireoide/efeitos dos fármacos , Tireotropina/metabolismo , Tireotropina/farmacologia , Tiroxina/metabolismo , Tiroxina/farmacologia , Tri-Iodotironina/metabolismo , Tri-Iodotironina/farmacologiaRESUMO
By analyzing the mechanisms that govern dopaminergic axon pathfinding from the midbrain to the striatum in embryonic rat brains, we identified neuroepithelial regions that exert chemotropic effects on mesencephalic dopaminergic axons. Explants from the pretectum and the striatum showed an attractive effect, whereas those from the midhindbrain boundary, the dorsal thalamus, and the ventral thalamus had no effect. Expression of semaphorin (Sema) 3C and Sema3F in the pretectum and of Sema3A in the striatum suggested a role for these axon guidance molecules in dopaminergic axon pathfinding. When expressed in HEK293 cell aggregates, Sema3C had an attractive effect and enhanced axon growth, Sema3A enhanced axon growth, and Sema3F had a repulsive effect on dopaminergic axons. Antineuropilin-1 and antineuropilin-2 antibodies reduced attraction by the pretectum, whereas attraction by the striatum was not affected by the presence of antineuropilin-1 antibodies. Moreover, neuropilin-1- and neuropilin-2-soluble Fc chimeras reduced the attraction by the pretectum. These results suggest that semaphorins may help to establish the dopaminergic projection from the midbrain to the striatum during embryonic development.
Assuntos
Axônios/fisiologia , Dopamina/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Mesencéfalo/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Semaforina-3A/fisiologia , Animais , Células Cultivadas , Feminino , Processamento de Imagem Assistida por Computador , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mesencéfalo/citologia , Neostriado/citologia , Neostriado/fisiologia , Proteínas do Tecido Nervoso/genética , Vias Neurais/citologia , Vias Neurais/crescimento & desenvolvimento , Neuropilina-1/antagonistas & inibidores , Neuropilina-1/metabolismo , Neuropilina-2/antagonistas & inibidores , Neuropilina-2/metabolismo , Gravidez , Ratos , Ratos Wistar , Semaforina-3A/genética , Transdução de Sinais/fisiologia , Colículos Superiores/citologia , Colículos Superiores/fisiologia , TransfecçãoRESUMO
We have addressed the control of longitudinal axon pathfinding in the developing hindbrain, including the caudal projections of reticular and raphe neurons. To test potential sources of guidance signals, we assessed axon outgrowth from embryonic rat hindbrain explants cultured in collagen gels at a distance from explants of midbrain-hindbrain boundary (isthmus), caudal hindbrain, or cervical spinal cord. Our results showed that the isthmus inhibited caudally directed axon outgrowth by 80% relative to controls, whereas rostrally directed axon outgrowth was unaffected. Moreover, caudal hindbrain or cervical spinal cord explants did not inhibit caudal axons. Immunohistochemistry for reticular and raphe neuronal markers indicated that the caudal, but not the rostral projections of these neuronal subpopulations were inhibited by isthmic explants. Companion studies in chick embryos showed that, when the hindbrain was surgically separated from the isthmus, caudal reticulospinal axon projections failed to form and that descending pioneer axons of the medial longitudinal fasciculus (MLF) play an important role in the caudal reticulospinal projection. Taken together, these results suggest that diffusible chemorepellent or nonpermissive signals from the isthmus and substrate-anchored signals on the pioneer MLF axons are involved in the caudal direction of reticulospinal projections and might influence other longitudinal axon projections in the brainstem.