Expression of matrix metalloproteinase-1 (MMP-1) in Wistar rat's intervertebral disc after experimentally induced scoliotic deformity

<p>Abstract</p> <p>Introduction</p> <p>A scoliotic deformity on intervertebral discs may accelerate degeneration at a molecular level with the production of metalloproteinases (MMPs). In the present experimental study we evaluated the presence of MMP-1 immunohistochemically after application of asymmetric forces in a rat intervertebral disc and the impact of the degree of the deformity on MMP-1 expression.</p> <p>Material-Method</p> <p>Thirty female Wistar rats (aged 2 months old, weighted 200 ± 10 grams) were used. All animals were age, weight and height matched. A mini Ilizarov external fixator was applied at the base of a rat tail under anaesthesia in order to create a scoliotic deformity of the intervertebral disc between the 9^thand 10^thvertebrae. Rats were divided into three groups according to the degree of the deformity. In group I, the deformity was 10°, in group II 30° and in group III 50°. The rats were killed 35 days after surgery. The discs were removed along with the neighbouring vertebral bodies, prepared histologically and stained immunohistochemically. Immunopositivity of disc's cells for MMP-1 was determined using a semi-quantitative scored system.</p> <p>Results</p> <p>MMP-1 immunopositivity was detected in disc cells of annulus fibrosus of all intervertebral disc specimens examined. The percentage of MMP-1 positive disc cells in annulus fibrosus in group I, II and III were 20%, 43% and 75%, respectively. MMP-1 positivity was significantly correlated with the degree of the deformity (p < 0,001). An increase of chondrocyte-like disc cells was observed in the outer annulus fibrosus and at the margin of the intervertebral disc adjacent to the vertebral end plates. The difference in the proportion of MMP-1 positive disc cells between the convex and the concave side was statistically not significant in group I (p = 0,6), in group II this difference was statistically significant (p < 0,01). In group III the concave side showed a remarkable reduction in the number of disc's cells and a severe degeneration of matrix microstructure.</p> <p>Conclusion</p> <p>The present study showed that an experimentally induced scoliotic deformity on a rat tail intervertebral disc results in over-expression of MMP-1, which is dependent on the degree of the deformity and follows a dissimilar distribution between the convex and the concave side.</p

Vesicular glutamate release from central axons contributes to myelin damage

Neuronal activity can lead to vesicular release of glutamate. Here the authors demonstrate that vesicular release of glutamate occurs in axons during ischemic conditions, and that an allosteric modulator of GluN2C/D is protective in models of ischemic injury

Tonic excitation or inhibition is set by GABAA conductance in hippocampal interneurons

Inhibition is a physiological process that decreases the probability of a neuron generating an action potential. The two main mechanisms that have been proposed for inhibition are hyperpolarization and shunting. Shunting results from increased membrane conductance, and it reduces the neuron-firing probability. Here we show that ambient GABA, the main inhibitory neurotransmitter in the brain, can excite adult hippocampal interneurons. In these cells, the GABAA current reversal potential is depolarizing, making baseline tonic GABAA conductance excitatory. Increasing the tonic conductance enhances shunting-mediated inhibition, which eventually overpowers the excitation. Such a biphasic change in interneuron firing leads to corresponding changes in the GABAA-mediated synaptic signalling. The described phenomenon suggests that the excitatory or inhibitory actions of the current are set not only by the reversal potential, but also by the conductance

Like mother, like child : investigating perinatal and maternal health stress in post-medieval London.

Post-Medieval London (sixteenth-nineteenth centuries) was a stressful environment for the poor. Overcrowded and squalid housing, physically demanding and risky working conditions, air and water pollution, inadequate diet and exposure to infectious diseases created high levels of morbidity and low life expectancy. All of these factors pressed with particular severity on the lowest members of the social strata, with burgeoning disparities in health between the richest and poorest. Foetal, perinatal and infant skeletal remains provide the most sensitive source of bioarchaeological information regarding past population health and in particular maternal well-being. This chapter examined the evidence for chronic growth and health disruption in 136 foetal, perinatal and infant skeletons from four low-status cemetery samples in post-medieval London. The aim of this study was to consider the impact of poverty on the maternal-infant nexus, through an analysis of evidence of growth disruption and pathological lesions. The results highlight the dire consequences of poverty in London during this period from the very earliest moments of life

Infectious and metabolic diseases: a synergistic bioarchaeology

Palaeopathologists have a long history of recording and interpreting evidence for infectious and metabolic diseases seen globally in preserved bodies and skeletons from archaeological sites. People today often experience co-morbidities, as did our ancestors, but little specific research in paleopathology has addressed synergies between these two categories of disease. The chapter starts by introducing these health challenges from a clinical perspective, and then considers the types of evidence used to detect them in the past, and the many methods available for recording and interpretation (macroscopic, biomolecular, histological, imaging, parasite analysis). This is followed by exploring links between leprosy and tuberculosis and vitamin D deficiency, leprosy and osteopenia/osteoporosis, the Developmental Origins Hypothesis and metabolic and infectious disease, and Paget’s disease of bone and infection. It is concluded that palaeopathology is in an excellent position, theoretically and methodologically, to contribute to our understanding of disease synergies in the past, thereby providing the evolutionary time depth for present understanding

Yeast Two‐Hybrid Studies

The yeast two-hybrid system is a high throughput method for the study of protein-protein interactions. The use and application of two GAL4 based and the CytoTrap Sos recruitment yeast two-hybrid systems are described. This includes a detailed consideration of appropriate baits together with their generation and characterization for use in the screening of cDNA libraries for the detection of interacting proteins, the characterization of positive clones resulting from cDNA library screens and strategies for the validation of protein-protein interactions using alternative experimental paradigms. © 2007 Springer Science+Business Media, LLC. All rights reserved