RESUMO
SUMMARY: The myodural bridge is a dense connective tissue connecting muscles and ligaments to the spinal dura mater in the atlanto-occipital interspace. Some researchers believe that the myodural bridge may play a vital physiological role. It is possible, for instance, that the prevention of spinal dura mater infoldings might be involved in regulated cerebrospinal fluid circulation. For instance, it is possible to prevent spinal dura mater infoldings, regulating cerebrospinal circulation. Bats are nocturnal and the only mammals that can perform a genuine and sustained flight, whereas tree shrews are arboreal mammals that often climb to a high altitude of about 10,000 feet. Both animals have lifestyles that are different from other previously studied mammals. The study of these two animals will shed further light on the existence of the myodural bridge in mammals. Gross anatomical dissection was used to observe the connections between the deep muscles of the neck and the dura mater at the level of the atlanto-occipital interspace. The existing structures were analyzed using conventional and special histological staining techniques. The suboccipital regions in bats and tree shrews contained the rectus capitis dorsal major (RCDma), rectus capitis dorsal minor (RCDmi), oblique capitis anterior (OCA), and oblique capitis posterior (OCP). Dense connective tissue connects the RCDmi to the posterior atlanto-occipital membrane (PAOM) and the latter to the spinal dura mater. The myodural bridge in these mammals shares a similar structure to the myodural bridge in humans. Histological analyses confirmed that the connective fibers of the myodural bridge were primarily type I collagen fibers. In this study, it is supplemented by the existence of the myodural bridge in mammals. This further demonstrates that myodural bridge widely exists in the normal anatomy of mammals. This provides morphological support for a comparative anatomical study of the physiological function of the myodural bridge.
El puente miodural es un tejido conjuntivo denso que conecta los músculos y los ligamentos a la duramadre espinal en el espacio atlanto-occipital. Algunos investigadores creen que el puente miodural puede desempeñar un papel fisiológico vital. Es posible, por ejemplo, que la prevención de los pliegues de la duramadre espinal pueda estar involucrada en la circulación regulada del líquido cefalorraquídeo. En esta instancia, es posible prevenir los pliegues de la duramadre espinal, regulando la circulación cerebro espinal. Los murciélagos son animales nocturnos y los únicos mamíferos que pueden realizar un vuelo real y sostenido, mientras que las musarañas arborícolas son mamíferos arbóreos que a menudo ascienden a una gran altura de unos 10 000 pies. Ambos animales tienen estilos de vida diferentes a los de otros mamíferos previamente estudiados. El estudio de estos dos animales ofrecerá más información sobre la existencia del puente miodural en los mamíferos. Se realizó una disección anatómica macroscópica para observar las conexiones entre los músculos profundos del cuello y la duramadre a nivel del espacio atlanto-occipital. Las estructuras existentes se analizaron mediante técnicas de tinción histológica convencionales y especiales. Las regiones suboccipitales en murciélagos y musarañas arbóreas presentaban el músculo recto dorsal mayor de la cabeza (RCDma), el recto dorsal menor de la cabeza (RCDmi), el oblicuo anterior de la cabeza (OCA) y el oblicuo posterior de la cabeza (OCP). El tejido conjuntivo denso conecta el RCDmi con la membrana atlanto- occipital posterior (PAOM) y esta última con la duramadre espinal. El puente miodural en estos mamíferos comparte una estructura similar al puente miodural en humanos. Los análisis histológicos confirmaron que las fibras conectivas del puente miodural son principalmente fibras de colágeno tipo I. Esto demuestra además que el puente miodural existe ampliamente en la anatomía normal de los mamíferos. Esta investigación proporciona apoyo morfológico para un estudio anatómico comparativo de la función fisiológica del puente miodural.
Assuntos
Animais , Tupaiidae/anatomia & histologia , Quirópteros/anatomia & histologia , Dura-Máter/anatomia & histologia , Anatomia ComparadaRESUMO
Aging is a major risk factor for the development of neurodegenerative diseases. Alzheimer's disease and other neurodegenerative diseases are characterized by abnormal and prominent protein aggregation in the brain, partially due to deficiency in protein clearance. It has been proposed that alterations in microglia phagocytosis and debris clearance hasten the onset of neurodegeneration. Dystrophic microglia are abundant in aged humans, and it has been associated with the onset of disease. Furthermore, alterations in microglia containing ferritin are associated with neurodegenerative conditions. To further understand the process of microglia dysfunction during the aging process, we used hippocampal sections from Tupaia belangeri (tree shrews). Adult (mean age 3.8 years), old (mean age 6 years), and aged (mean age 7.5 years) tree shrews were used for histochemical and immunostaining techniques to determine ferritin and Iba1 positive microglia, iron tissue content, tau hyperphosphorylation and oxidized-RNA in dentate gyrus, subiculum, and CA1-CA3 hippocampal regions. Our results indicated that aged tree shrews presented an increased number of activated microglia containing ferritin, but microglia labeled with Iba1 with a dystrophic phenotype was more abundant in aged individuals. With aging, oxidative damage to RNA (8OHG) increased significantly in all hippocampal regions, while tau hyperphosphorylation (AT100) was enhanced in DG, CA3, and SUB in aged animals. Phagocytic inclusions of 8OHG- and AT100-damaged cells were observed in activated M2 microglia in old and aged animals. These data indicate that aged tree shrew may be a suitable model for translational research to study brain and microglia alterations during the aging process.
Assuntos
Microglia , Tupaia , Animais , Criança , Pré-Escolar , Ferritinas , Hipocampo , Humanos , Estresse Oxidativo , RNA , TupaiidaeRESUMO
The discovery of new drugs requires the development of improved animal models for drug testing. The Chinese tree shrew is considered to be a realistic candidate model. To assess the potential of the Chinese tree shrew for pharmacological testing, we performed drug target prediction and analysis on genomic and transcriptomic scales. Using our pipeline, 3,482 proteins were predicted to be drug targets. Of these predicted targets, 446 and 1,049 proteins with the highest rank and total scores, respectively, included homologs of targets for cancer chemotherapy, depression, age-related decline and cardiovascular disease. Based on comparative analyses, more than half of drug target proteins identified from the tree shrew genome were shown to be higher similarity to human targets than in the mouse. Target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets. We developed an effective pipeline and search strategy for drug target prediction and the evaluation of model-based target identification for drug testing. This work provides useful information for future studies of the Chinese tree shrew as a source of novel targets for drug discovery research.
Assuntos
Descoberta de Drogas/métodos , Modelos Animais , Preparações Farmacêuticas/metabolismo , Proteínas/metabolismo , Tupaiidae , Análise de Variância , Animais , China , Sistemas de Liberação de Medicamentos/métodos , Perfilação da Expressão Gênica , Humanos , Camundongos , Anotação de Sequência MolecularRESUMO
Adrenal corticosteroids influence the function of the hippocampus, the brain structure in which the highest expression of glucocorticoid receptors is found. Chronic high levels of cortisol elicited by stress or through exogenous administration can cause irreversible damage and cognitive deficits. In this study, we searched for genes expressed in the hippocampal formation after chronic cortisol treatment in male tree shrews. Animals were treated orally with cortisol for 28 days. At the end of the experiments, we generated two subtractive hippocampal hybridization libraries from which we sequenced 2,246 expressed sequenced tags (ESTs) potentially regulated by cortisol. To validate this approach further, we selected some of the candidate clones to measure mRNA expression levels in hippocampus using real-time PCR. We found that 66% of the sequences tested (10 of 15) were differentially represented between cortisol-treated and control animals. The complete set of clones was subjected to a bioinformatic analysis, which allowed classification of the ESTs into four different main categories: 1) known proteins or genes (approximately 28%), 2) ESTs previously published in the database (approximately 16%), 3) novel ESTs matching only the reference human or mouse genome (approximately 5%), and 4) sequences that do not match any public database (50%). Interestingly, the last category was the most abundant. Hybridization assays revealed that several of these clones are indeed expressed in hippocampal tissue from tree shrew, human, and/or rat. Therefore, we discovered an extensive inventory of new molecular targets in the hippocampus that serves as a reference for hippocampal transcriptional responses under various conditions. Finally, a detailed analysis of the genomic localization in human and mouse genomes revealed a survey of putative novel splicing variants for several genes of the nervous system.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hidrocortisona/administração & dosagem , Animais , Clonagem Molecular/métodos , Esquema de Medicação , Etiquetas de Sequências Expressas , Perfilação da Expressão Gênica/métodos , Biblioteca Gênica , Hipocampo/fisiologia , Humanos , Hibridização In Situ/métodos , Masculino , RNA Mensageiro/biossíntese , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , TupaiidaeRESUMO
Analysis of differentially expressed genes in the brain is a promising tool for elucidating pathological mechanisms that lead to central nervous disorders. Stress is known to be involved in the development of psychopathologies such as depression. In the present study, we searched for differentially expressed genes in the hippocampal formation after chronic psychosocial stress and after treatment with the antidepressant clomipramine. Experiments were conducted in male tree shrews, a valid psychosocial stress model in which antidepressant drugs prevent diverse effects of stress. Because many effects of stress have been attributed to the stress-induced elevation in glucocorticoids, we screened two subtractive hippocampal cDNA libraries generated from RNA of chronic cortisol-treated animals. Using real-time PCR to measure mRNA amounts, we identified five sequences whose expression levels differed between stressed animals and controls. Transcript levels of four of them, nerve growth factor (NGF), membrane glycoprotein 6a (M6a), CDC-like kinase 1 (CLK-1) and G-protein alpha q (GNAQ) were reduced by chronic psychosocial stress. Reduced amounts of these genes, which are all related to processes of cell differentiation, is in agreement with previous findings showing a retraction of dendrites and an impairment of neurogenesis in the hippocampal formation after chronic stress. An additional expressed sequence that was also regulated by stress could not be assigned to any known gene. Treatment with the antidepressant clomipramine prevented stress effects on expression of M6a, CLK-1, GNAQ and the novel sequence, but showed no effect on NGF stress-induced down-regulation. These findings support the concept that depressive disorders are accompanied by processes of neuronal dedifferentiation, at least in the hippocampal formation, and that antidepressants prevent these processes.