Synaptic plasticity at the interface of health and disease: New insights on the role of endoplasmic reticulum intracellular calcium stores.

Work from the past 40years has unraveled a wealth of information on the cellular and molecular mechanisms underlying synaptic plasticity and their relevance in physiological brain function. At the same time, it has been recognized that a broad range of neurological diseases may be accompanied by severe alterations in synaptic plasticity, i.e., 'maladaptive synaptic plasticity', which could initiate and sustain the remodeling of neuronal networks under pathological conditions. Nonetheless, our current knowledge on the specific contribution and interaction of distinct forms of synaptic plasticity (including metaplasticity and homeostatic plasticity) in the context of pathological brain states remains limited. This review focuses on recent experimental evidence, which highlights the fundamental role of endoplasmic reticulum-mediated Ca(2+) signals in modulating the duration, direction, extent and type of synaptic plasticity. We discuss the possibility that intracellular Ca(2+) stores may regulate synaptic plasticity and hence behavioral and cognitive functions at the interface between physiology and pathology.

In vivo study on critical defects using the sheep model.

Bone grafting procedures are widely used to repair large defects successfully in humans, but new surgical therapies can be designed to improve allograft integration. The objective of this study was to investigate the best surgical procedure to study bone graft integration in a large animal model. An osteoperiosteal defect of 3 cm in the tibia or in the metatarsal was made in 15 adult crossbreed sheep to investigate osteo-integration of a homologous bone graft in an intercalary critical defect. DCP plates, alone or in association with Scotchcast or external fixator were used as fixation devices. The Scotchcast as was applied after surgery and left for 2 months to avoid torsion stress of the limb during the stand up movement. Metatarsal defect fixed with 7-hole DCP plate and protected with Scotchcast was the best surgical approach to avoid early or late implant failures, and provided good radiographic results after 4 months.

Tissue-transglutaminase in rat and human brain: light and electron immunocytochemical analysis and in situ hybridization study.

Tissue-type transglutaminases constitute a family of enzymes having a dual role. They catalyze the post-translational modification of proteins and play a role in signal transduction pathways, several isoforms have been cloned in the brain. Many in vitro experiments and post-mortem studies have claimed that the enzyme plays a central role in the development of neurodegenerative disorders, especially in CAG-triplet diseases. In the present investigation, we conducted an immunocytochemical study using two different antibodies raised against tissue-type transglutaminase. To confirm the enzyme expression, non-radioactive in situ hybridization was performed on adjacent sections. The study was completed by analyzing the ultrastructural localization of the enzyme by electron microscopy. Tissue-type transglutaminase was widely expressed in both the human and rat brain. Many positive cells exhibiting neuronal features were found in the brain and cerebellum. There was a preferential expression in elements of pyramidal and extrapyramidal pathways with less expression in the somatosensory system. The mRNA detection confirmed the distribution of the enzyme. The ultrastructural approach revealed the presence of the enzyme in all neuronal compartments. Light and electron microscopy studies showed the ubiquitous nature of the enzyme and its putative role in functional as well as putative pathological processes.