Genetic approaches to probe spatial coding in the medial entorhinal cortex

The medial entorhinal cortex is a key component of the brain’s spatial navigation and memory system. It is the site where grid cells were discovered, i.e. neurons that are active at several locations in an environment, thus giving rise to a hexagonal ’grid’-like firing pattern. Experimental evidence suggests that inputs from the hippocampus, medial septum, and other brain regions, together with specific local connectivity are factors that contribute to the emergence of the grid cell pattern. To date, it is not clear how the hippocampus, which is also involved in spatial behaviors and projects to the MEC, contributes to grid cell function. I addressed this question by recording grid cells in mice with impaired hippocampal function. My results suggest that impaired spatial hippocampal coding does not disrupt grid cell firing. Furthermore, I gathered evidence that the MEC, as opposed to the hippocampus, is required for path integration. To probe how specific MEC neurons support spatial behavior, we need tools to manipulate them selectively. To this end, molecular markers must be identified and assigned to functional cell types. Two promising candidates are reelin (RE) and calbindin (CB). These proteins are expressed in anatomically distinct cell types. While in vitro these neurons are distinct with respect to their electrophysio- logical properties, it is still unclear how these differences correlate to in vivo firing patterns. I addressed this question by using two mouse lines to optogenetically tag RE + and CB + neurons. I find no major difference between the two populations, except for the pattern of projections to other brain regions. Also, I reveal the existence of a previously unknown projection from the parasubiculum to the contralateral MEC, that, along with pyramidal CB + neuron projections, appear to inhibit the contralateral MEC. These results suggest that the firing patterns of RE + and CB + cells are surprisingly similar, and that these markers may be valuable tools for studying components of cross-hemispheric connections

Oxidative Stress Produced by Urban Atmospheric Nanoparticles

In urban areas, the diesel-fuelled and bio-fuelled vehicles represent the major sources of nanoparticles complemented by nanotechnology with different types of particles, in addition to natural and to other anthropogenic sources. The atmospheric nanoparticles differ in composition, size, shape or oxidant capacity, presenting a large variability that causes difficulties in their measurements and health impact identification. The oxidative stress can be initiated by atmospheric nanoparticles through different mechanisms: interaction between nanoparticles and tissue cells, cellular internalisation of nanoparticles, activation of signalling pathways, decrease of the cellular antioxidants, activation of the pro-inflammatory cascade, lipid peroxidation, activation of cellular signalling pathway that leads to apoptosis, etc. Ultrafine particles (<100 nm) represent ~80% of the total atmospheric particles and produce inflammation through oxidative stress mechanisms. The atmospheric nanoparticles can penetrate the skin and can be inhaled or ingested affecting different organs and leading to different diseases: neurodegeneration, thrombogenesis, atherosclerosis, asthma, lung cancer, heart arrest, etc

Alterations in Calcium Signaling Pathways in Breast Cancer

Breast cancer is the second most common cancer in women and the fifth cause contributing to death due to the cancer condition. It is essential to deeply understand the complex cellular mechanisms leading to this disease. There are multiple connections between calcium homeostasis alterations and breast cancer in the literature, but no consensus links the mechanism to the disease prognosis. Among the cells contributing to the breast cancer are the breast telocytes, which connect through gap junctions to other cells, including cancer cells and myoepithelial cells. Multiple proteins (i.e., voltage-gated calcium channels, transient receptor potential channels, STIM and Orai proteins, ether à go-go potassium channels, calcium-activated potassium channels, calcium-activated chloride channels, muscarinic acetylcholine receptors, etc.) coupled with calcium signaling pathways undergo functional and/or expression changes associated with breast cancer development and progression, and might represent promising pharmacological targets. Unraveling the mechanisms of altered calcium homeostasis in various breast cells due to the cancer condition might contribute to personalized therapeutic approaches

Skeletal Muscle Stem Cell Niche from Birth to Old Age

Stem cells are defined as undifferentiated cells that are able to unlimitedly renew themselves within controlled conditions and to differentiate into a multitude of mature cell types. Skeletal muscle stem cells, represented predominantly by satellite cells, show a variable capability of self-renewal and myogenic differentiation. They were found to be involved not only in the growth of myofibers during neonatal and juvenile life but also in the regeneration of skeletal muscles after an injury. The microenvironment in which stem cells are nourished and maintained dormant preceding division and differentiation is known as “niche.” The niche consists of myofibers, which are believed to modulate the active/inactive state of the stem cells, extracellular matrix, neural networks, blood vessels, and a multitude of soluble molecules. It was observed that changes in the composition of the niche have an impact on the stem cell functions and hierarchy. Furthermore, it seems that its layout is variable throughout the entire life, translating into a decrease in the regenerative capacity of satellite cells in aged tissues. The scope of this chapter is to provide a detailed view of the changes that occur in the skeletal stem cell niche during life and to analyze their implications on tissue regeneration. Future studies should focus on developing new therapeutic tools for diseases involving muscle atrophy

Acute Fatty Liver of Pregnancy

Acute fatty liver of pregnancy (AFLP) is a rare but life-threatening condition that develops in the third trimester of pregnancy. AFLP shares similar clinical features with other more common pregnancy-associated conditions. However, early correct diagnosis is important for maternal and fetal survival. Once the diagnosis has been established, immediate delivery and maternal intensive support should be undertaken. Both parents and the infant should be tested for deficiencies of the mitochondrial fatty acid oxidation, especially for long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, as many cases of AFLP are related to disruption of this physiological enzymatic pathway

The Telocytes in the Subepicardial Niche

A great interest has developed over the last several years in research on interstitial Cajal-like cells (ICLCs), later renamed to telocytes (TCs). Such studies are restricted by diverse limitations. We aimed to critically review (sub)epicardial ICLCs/TCs and to bring forward supplemental immunohistochemical evidence on (sub)epicardial stromal niche inhabitants. We tested the epicardial expressions of CD117/c-kit, CD34, Cytokeratin 7 (CK7), Ki67, Platelet-Derived Growth Factor Receptor (PDGFR)-&#945; and D2-40 in adult human cardiac samples. The mesothelial epicardial cells expressed D2-40, CK7, CD117/c-kit and PDGFR-&#945;. Subepicardial D2-40-positive lymphatic vessels and isolated D2-40-positive and CK7-positive subepicardial cells were also found. Immediate submesothelial spindle-shaped cells expressed Ki-67. Submesothelial stromal cells and endothelial tubes were PDGFR-&#945;-positive and CD34-positive. The expression of CD34 was pan-stromal, so a particular stromal cell type could not be distinguished. The stromal expression of CD117/c-kit was also noted. It seems that epicardial TCs could not be regarded as belonging to a unique cell type until (pre)lymphatic endothelial cells are inadequately excluded. Markers such as CD117/c-kit or CD34 seem to be improper for identifying TCs as a distinctive cell type. Care should be taken when using the immunohistochemical method and histological interpretations, as they may not produce accurate results

Prenatal Diagnosis and Outcome of Tracheal Agenesis as Part of Congenital High Airway Obstruction Syndrome. Case Presentation and Literature Review

Tracheal atresia is an extremely rare condition whereby a partial or total obstruction of the trachea is seen. It is almost always lethal, with just a handful of cases that ended with a good outcome. In this study we report on a 15-week male fetus, diagnosed with hyperechogenic lungs, midline heart position and inverted diaphragm. Sonographic findings suggest congenital High Airway Obstruction Syndrome (CHAOS) An ultrasound scan and fetal MRI were not able to point out the exact obstruction level. In spite of extensive counselling, the parents opted to carry on with the pregnancy. Fetal demise was noted on a scan at 19 weeks gestation. After the elective termination of pregnancy, a post-mortem examination showed partial tracheal atresia with no other anomalies. Despite technological progress in CHAOS syndrome, a precise diagnosis and accurate prognosis remain elusive

POSTHERPETIC NEURALGIA – CURRENT FACTS AND THERAPEUTIC POSSIBILITIES

Neuropathic pain in postherpetic neuralgia has an impact on important aspects of the patient’s day to day life, lowering it’s quality. Understanding the complex pathophysiological mechanisms of postherpetic neuralgia and assesing the patient’s pain profile helps optimize the individualized, multimodal analgesic therapy that acts at different levels along the pain pathway. This paper is a review of the latest data in the literature regarding the pathophysiological mechanisms that lead to the emerging and evolution of postherpetic neuralgia and the up to date therapeutic possibilities

Prenatal Diagnosis and Outcome of Tracheal Agenesis as Part of Congenital High Airway Obstruction Syndrome. Case Presentation and Literature Review

Tracheal atresia is an extremely rare condition whereby a partial or total obstruction of the trachea is seen. It is almost always lethal, with just a handful of cases that ended with a good outcome. In this study we report on a 15-week male fetus, diagnosed with hyperechogenic lungs, midline heart position and inverted diaphragm. Sonographic findings suggest congenital High Airway Obstruction Syndrome (CHAOS) An ultrasound scan and fetal MRI were not able to point out the exact obstruction level. In spite of extensive counselling, the parents opted to carry on with the pregnancy. Fetal demise was noted on a scan at 19 weeks gestation. After the elective termination of pregnancy, a post-mortem examination showed partial tracheal atresia with no other anomalies. Despite technological progress in CHAOS syndrome, a precise diagnosis and accurate prognosis remain elusive

THE PROBLEM OF DIAGNOSING VITAMIN B12 DEFICIENCY

Vitamin B12 deficiency (cobalamin) is a common cause of megaloblastic anemia, with various neuropsychiatric symptoms. The prevalence is not known with certainty, but the incidence seems to increase with age. The diagnosis is usually based on the identification of a low serum level of vitamin B12 with clinical evidence of deficiency and with a good response to vitamin B12 replacement therapy. When confirming the diagnosis, consideration should be given to the etiology that may be due to nutritional deficiency, malabsorption and other gastrointestinal causes