Changes in the Dentate Gyrus Gene Expression Profile Induced by Levetiracetam Treatment in Rats with Mesial Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy. Levetiracetam (LEV) is an antiepileptic drug whose mechanism of action at the genetic level has not been fully described. Therefore, the aim of the present work was to evaluate the relevant gene expression changes in the dentate gyrus (DG) of LEV-treated rats with pilocarpine-induced TLE. Whole-transcriptome microarrays were used to obtain the differential genetic profiles of control (CTRL), epileptic (EPI), and EPI rats treated for one week with LEV (EPI + LEV). Quantitative RT-qPCR was used to evaluate the RNA levels of the genes of interest. According to the results of the EPI vs. CTRL analysis, 685 genes were differentially expressed, 355 of which were underexpressed and 330 of which were overexpressed. According to the analysis of the EPI + LEV vs. EPI groups, 675 genes were differentially expressed, 477 of which were downregulated and 198 of which were upregulated. A total of 94 genes whose expression was altered by epilepsy and modified by LEV were identified. The RT-qPCR confirmed that LEV treatment reversed the increased expression of Hgf mRNA and decreased the expression of the Efcab1, Adam8, Slc24a1, and Serpinb1a genes in the DG. These results indicate that LEV could be involved in nonclassical mechanisms involved in Ca2+ homeostasis and the regulation of the mTOR pathway through Efcab1, Hgf, SLC24a1, Adam8, and Serpinb1a, contributing to reduced hyperexcitability in TLE patients.

Vascular Tissues Distribution Affects Calcium and Calcium Oxalate Crystals in Fruits of Wild Tomato (Lycopersicon pimpinellifolium (L.) Mill.).

Tomato fruit is an excellent model for evaluating calcium regulation in plants since it expresses symptoms of either calcium deficiency or calcium excess. Aiming to evaluate the structure of the vascular system and its interactions with calcium and calcium oxalate crystals (CaOx), fruits of Lycopersicon pimpinellifolium were studied. Calcium levels were evaluated in basal, median, and distal pericarp portions, which were also analyzed under a light microscope to describe the structure. The L. pimpinellifolium pericarp shows idioblasts with calcium oxalate crystals. Vascular bundles of the basal pericarp show large transverse sections and abundant xylem vessels. The vascular bundles were smaller in the distal pericarp, and the xylem showed fewer and narrower vessels. The terminal bundles often consisted exclusively of phloem. Despite the differences observed in vascular bundle composition, the density of the vascular system was uniform in the pericarp as a consequence of bundle ramifications that occur at distal portions. The calcium concentration and crystal idioblasts decrease towards the apex of the fruit. The reduction in the xylem:phloem ratio seems to determine the low calcium concentration in the distal fruit portion.

Could Lower Testosterone in Older Men Explain Higher COVID-19 Morbidity and Mortalities?

The health scourge imposed on humanity by the COVID-19 pandemic seems not to recede. This fact warrants refined and novel ideas analyzing different aspects of the illness. One such aspect is related to the observation that most COVID-19 casualties were older males, a tendency also noticed in the epidemics of SARS-CoV in 2003 and the Middle East respiratory syndrome in 2012. This gender-related difference in the COVID-19 death toll might be directly involved with testosterone (TEST) and its plasmatic concentration in men. TEST has been demonstrated to provide men with anti-inflammatory and immunological advantages. As the plasmatic concentration of this androgen decreases with age, the health benefit it confers also diminishes. Low plasmatic levels of TEST can be determinant in the infection's outcome and might be related to a dysfunctional cell Ca2+ homeostasis. Not only does TEST modulate the activity of diverse proteins that regulate cellular calcium concentrations, but these proteins have also been proven to be necessary for the replication of many viruses. Therefore, we discuss herein how TEST regulates different Ca2+-handling proteins in healthy tissues and propose how low TEST concentrations might facilitate the replication of the SARS-CoV-2 virus through the lack of modulation of the mechanisms that regulate intracellular Ca2+ concentrations.

Transient Receptor Potential Channels in Microglia: Roles in Physiology and Disease.

Microglia modulate the nervous system cellular environment and induce neuroprotective and neurotoxic effects. Various molecules are involved in these processes, including families of ion channels expressed in microglial cells, such as transient receptor potential (TRP) channels. TRP channels comprise a family of non-selective cation channels that can be activated by mechanical, thermal, and chemical stimuli, and which contribute to the regulation of intracellular calcium concentrations. TRP channels have been shown to be involved in cellular processes such as osmotic regulation, cytokine production, proliferation, activation, cell death, and oxidative stress responses. Given the significance of these processes in microglial activity, studies of TRP channels in microglia have focused on determining their roles in both neuroprotective and neurotoxic processes. TRP channel activity has been proposed to play an important function in neurodegenerative diseases, ischemia, inflammatory responses, and neuropathic pain. Modulation of TRP channel activity may thus be considered as a potential therapeutic strategy for the treatment of various diseases associated with alterations of the central nervous system (CNS). In this review, we describe the expression of different subfamilies of TRP channels in microglia, focusing on their physiological and pathophysiological roles, and consider their potential use as therapeutic targets in CNS diseases.

Preterm labour: association between labour physiology, tocolysis and prevention.

INTRODUCTION: In developed countries, preterm birth is the major cause of perinatal morbidity, mortality and the most important public health problem in the obstetric field. In the past decades, an increasing trend has been observed regardless of the great efforts focussed on the improvement of our understanding of the physiopathological mechanisms behind preterm labour (PTL) and the improvement in the use of tocolytic drugs. AREAS COVERED: In this review, the authors focus on some points of the physiopathology of labour in order to understand the rationality behind the different management approaches developed for the PTL syndrome. EXPERT OPINION: There is a need to develop new tools for the treatment of patients with PTL. Research focussed on improving tocolysis, the physiology of labour and pathological processes involved in PTL would afford new approaches for the treatment of PTL, allowing clinicians to provide integrative solutions for this multifactorial disease. Recently, the prophylactic use of progesterone pessary and cerclage in women with high risk of premature labour has been reported to reduce the incidence of premature births and improve neonatal outcomes. These results highlight the importance of prediction models in order to establish preventative strategies early in pregnancy.