scholarly journals X-Linked Lissencephaly With Absent Corpus Callosum and Abnormal Genitalia

2017 ◽  
Vol 4 ◽  
pp. 2329048X1773862 ◽  
Author(s):  
David Coman ◽  
Tom Fullston ◽  
Cheryl Shoubridge ◽  
Richard Leventer ◽  
Flora Wong ◽  
...  
Keyword(s):  
Chronic Diarrhea ◽  
Pancreatic Insufficiency ◽  
Homeobox Gene ◽  
Failure To Thrive ◽  
Hypothalamic Dysfunction ◽  
The Central Nervous System ◽  
Enteroendocrine System ◽  
Multisystem Manifestations

X-linked lissencephaly with abnormal genitalia is a rare and devastating syndrome. The authors present an infant with a multisystem phenotype where the intestinal manifestations were as life limiting as the central nervous system features. Severe chronic diarrhea resulted in failure to thrive, dehydration, electrolyte derangements, long-term hospitalization, and prompted transition to palliative care. Other multisystem manifestations included megacolon, colitis, pancreatic insufficiency hypothalamic dysfunction, hypothyroidism, and hypophosphatasia. A novel aristaless-related homeobox gene mutation, c.1136G>T/p.R379L, was identified. This case contributes to the clinical, histological, and molecular understanding of the multisystem nature of this disorder, especially the role of ARX in the development of the enteroendocrine system.

Neurotrophins and Proneurotrophins: Focus on Synaptic Activity and Plasticity in the Brain

2017 ◽  
Vol 23 (6) ◽  
pp. 587-604 ◽  
Author(s):  
Julien Gibon ◽  
Philip A. Barker
Keyword(s):  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Cellular Processes ◽  
Term Potentiation ◽  
Neurotrophin 3 ◽  
New Findings ◽  
The Central Nervous System ◽  
The Brain

Neurotrophins have been intensively studied and have multiple roles in the brain. Neurotrophins are first synthetized as proneurotrophins and then cleaved intracellularly and extracellularly. Increasing evidences demonstrate that proneurotrophins and mature neurotrophins exerts opposing role in the central nervous system. In the present review, we explore the role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4) and their respective proform in cellular processes related to learning and memory. We focused on their roles in synaptic activity and plasticity in the brain with an emphasis on long-term potentiation, long-term depression, and basal synaptic transmission in the hippocampus and the temporal lobe area. We also discuss new findings on the role of the Val66Met polymorphism on the BDNF propeptide on synaptic activity.

scholarly journals The role of Neuropilin-1 in COVID-19

2021 ◽  
Vol 17 (1) ◽  
pp. e1009153
Author(s):  
Bindu S. Mayi ◽  
Jillian A. Leibowitz ◽  
Arden T. Woods ◽  
Katherine A. Ammon ◽  
Alphonse E. Liu ◽  
...  
Keyword(s):  
Immune Function ◽  
Viral Entry ◽  
Axonal Guidance ◽  
Cell Surface Receptor ◽  
Neuropilin 1 ◽  
Surface Receptor ◽  
The Central Nervous System

Neuropilin-1 (NRP-1), a member of a family of signaling proteins, was shown to serve as an entry factor and potentiate SARS Coronavirus 2 (SARS-CoV-2) infectivity in vitro. This cell surface receptor with its disseminated expression is important in angiogenesis, tumor progression, viral entry, axonal guidance, and immune function. NRP-1 is implicated in several aspects of a SARS-CoV-2 infection including possible spread through the olfactory bulb and into the central nervous system and increased NRP-1 RNA expression in lungs of severe Coronavirus Disease 2019 (COVID-19). Up-regulation of NRP-1 protein in diabetic kidney cells hint at its importance in a population at risk of severe COVID-19. Involvement of NRP-1 in immune function is compelling, given the role of an exaggerated immune response in disease severity and deaths due to COVID-19. NRP-1 has been suggested to be an immune checkpoint of T cell memory. It is unknown whether involvement and up-regulation of NRP-1 in COVID-19 may translate into disease outcome and long-term consequences, including possible immune dysfunction. It is prudent to further research NRP-1 and its possibility of serving as a therapeutic target in SARS-CoV-2 infections. We anticipate that widespread expression, abundance in the respiratory and olfactory epithelium, and the functionalities of NRP-1 factor into the multiple systemic effects of COVID-19 and challenges we face in management of disease and potential long-term sequelae.

scholarly journals Metabolic Reprogramming and Cell Adhesion in Acute Leukemia Adaptation to the CNS Niche

2021 ◽  
Vol 9 ◽  
Author(s):  
Nitesh D. Sharma ◽  
Esra’a Keewan ◽  
Ksenia Matlawska-Wasowska
Keyword(s):  
Cell Adhesion ◽  
Acute Leukemia ◽  
Poor Prognosis ◽  
Significant Risk ◽  
Leukemic Cell ◽  
Metabolic Reprogramming ◽  
Leukemic Cells ◽  
The Central Nervous System

Involvement of the Central Nervous System (CNS) in acute leukemia confers poor prognosis and lower overall survival. Existing CNS-directed therapies are associated with a significant risk of short- or long-term toxicities. Leukemic cells can metabolically adapt and survive in the microenvironment of the CNS. The supporting role of the CNS microenvironment in leukemia progression and dissemination has not received sufficient attention. Understanding the mechanism by which leukemic cells survive in the nutrient-poor and oxygen-deprived CNS microenvironment will lead to the development of more specific and less toxic therapies. Here, we review the current literature regarding the roles of metabolic reprogramming in leukemic cell adhesion and survival in the CNS.

The Role of Endocannabinoid Signaling in Motor Control

Physiology ◽  
2010 ◽  
Vol 25 (4) ◽  
pp. 230-238 ◽  
Author(s):  
A. El Manira ◽  
A. Kyriakatos
Keyword(s):  
Central Nervous System ◽  
Motor Skills ◽  
Motor System ◽  
Cannabinoid Receptors ◽  
Retrograde Signaling ◽  
Motor Circuits ◽  
The Central Nervous System ◽  
Different Parts

Cannabinoid receptors and endocannabinoid signaling are distributed throughout the rostrocaudal neuraxis. Retrograde signaling via endocannabinoid mediates synaptic plasticity in many regions in the central nervous system. Here, we review the role of endocannabinoid signaling in different parts of the vertebrate motor system from networks responsible for the execution of movement to planning centers in the basal ganglia and cortex. The ubiquity of endocannabinoid-mediated plasticity suggests that it plays an important role in producing motion from defined circuitries and also for reconfiguring networks to learn new motor skills. The long-term plasticity induced by endocannabinoids may provide a long-term buffer that stabilizes the organization of motor circuits and their activity.

scholarly journals Effects of ZIKV + IgG+ complex on murine microglial cells

2021 ◽  
Author(s):  
Giulia Pinzetta ◽  
Nicole Bernd Becker ◽  
Felipe Krimberg ◽  
Ângela Zanatta ◽  
Laura Siqueira ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Microglial Activation ◽  
Ros Production ◽  
Transplacental Transmission ◽  
Igg Antibodies ◽  
Murine Microglia ◽  
The Central Nervous System ◽  
Complex Methods

Background: Infection by Zika virus (ZIKV) is associated with damage to the Central Nervous System, such as Congenital Zika Syndrome1 . Due to its transplacental transmission, ZIKV induces neuroinflammation and microglial activation, resulting in lesions that can compromise neurodevelopment2-4. The fetus protection can be provided by maternal antibodies. However, this protection is still controversial5 . In this context, it is necessary to elucidate the effects of ZIKV and the mechanisms involved. Objectives: The present work aim to evaluate the role of the ZIKV+IgG+ complex in murine microglia cells (BV2). Design and setting: BV2 were exposed for 24 or 72 hours, to ZIKV, ZIKA-IgG+ or ZIKV+IgG+ complex. Methods: Effects of exposure to treatments were evaluated by MTT, oxidation of DCFHDA (ROS production)6 and mitochondrial membrane potential (Δ∴ϑ), measured by JC-17 assay. Results: It was observed that ZIKV-IgG+ and the ZIKV+IgG+ complex are cytotoxic to microglia, impairing the viability of these cells, altering Δ∴ϑ and inducing the production of ROS, especially in long-term exposure8,9. Negative action mediated by these antibodies may be a result of oxidative stress and a intervention in the Δ∴ϑ. Conclusion: ZIKV-IgG+ antibodies are harmful to microglia and these mechanisms may be related to the potential for ZIKV neuroinflammation.

scholarly journals Role of Vitamin E and the Orexin System in Neuroprotection

2021 ◽  
Vol 11 (8) ◽  
pp. 1098
Author(s):  
Maria Ester La Torre ◽  
Ines Villano ◽  
Marcellino Monda ◽  
Antonietta Messina ◽  
Giuseppe Cibelli ◽  
...  
Keyword(s):  
Vitamin E ◽  
Neurodegenerative Diseases ◽  
Antioxidant Properties ◽  
Phenotypic Change ◽  
The Central Nervous System ◽  
Specific Receptors

Microglia are the first line of defense at the level of the central nervous system (CNS). Phenotypic change in microglia can be regulated by various factors, including the orexin system. Neuroinflammation is an inflammatory process mediated by cytokines, by the lack of interaction of specific receptors such as the OX2-OX2R complex, caused by systemic tissue damage or, more often, associated with direct damage to the CNS. Chronic activation of microglia could lead to long-term neurodegenerative diseases. This review aims to explore how tocopherol (vitamin E) and the orexin system may play a role in the prevention and treatment of microglia inflammation and, consequently, in neurodegenerative diseases thanks to its antioxidant properties. The results of animal and in vitro studies provide evidence to support the use of tocopherol for a reduction in microglia inflammation as well as a greater activation of the orexinergic system. Although there is much in vivo and in vitro evidence of vitamin E antioxidant and protective abilities, there are still conflicting results for its use as a treatment for neurodegenerative diseases that speculate that vitamin E, under certain conditions or genetic predispositions, can be pro-oxidant and harmful.

scholarly journals Central Precocious Puberty in Boys and Girls: Similarities and Differences

Sexes ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 119-131
Author(s):  
Cristina Mucaria ◽  
Nina Tyutyusheva ◽  
Giampiero I. Baroncelli ◽  
Diego Peroni ◽  
Silvano Bertelloni
Keyword(s):  
Precocious Puberty ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Gnrh Analog ◽  
Secondary Sexual Characteristics ◽  
Sexual Characteristics ◽  
The Central Nervous System

Central precocious puberty (CPP) is due to the premature activation of the hypothalamic–pituitary–gonadal axis, which is responsible for the appearance of secondary sexual characteristics. It occurs before the age of 8 and 9 in girls and boys, respectively. CPP shows higher incidence in females than in males. Causes of CPP are similar in both sexes, but the idiopathic form is more frequent in girls, while organic forms are more frequent in males. Recent studies demonstrated a role of some genetic variants in the pathogenesis of CPP. The diagnostic evaluation based on accurate physical examination, assessment of the pituitary–gonadal axis, pelvic sonography in girls, and determination of bone age. Magnetic resonance of the central nervous system should be done in all boys and selected girls. Since the 1980s, pharmacologic treatment involves the use of gonadotropin-releasing hormone (GnRH) analogs. These drugs are characterized by few side effects and long-term safety. Many data are available on the outcome of GnRH analog treated female patients, while poor data are reported in boys. Adult height is improved in both sexes.

scholarly journals Large-Volume Intrathecal Administrations: Impact on CSF Pressure and Safety Implications

2021 ◽  
Vol 15 ◽  
Author(s):  
Vasily Belov ◽  
Janine Appleton ◽  
Stepan Levin ◽  
Pilar Giffenig ◽  
Beata Durcanova ◽  
...  
Keyword(s):  
Large Volume ◽  
Biological Effects ◽  
Dependent Manner ◽  
Key Factors ◽  
Contributing Factors ◽  
Csf Pressure ◽  
The Central Nervous System ◽  
Different Levels

The increasing number of studies demonstrates the high potency of the intrathecal (IT) route for the delivery of biopharmaceuticals to the central nervous system (CNS). Our earlier data exhibited that both the infused volume and the infusion rate can regulate the initial disposition of the administered solute within the cerebrospinal fluid (CSF). This disposition is one of key factors in defining the subsequent transport of the solute to its intended target. On the other hand, fast additions of large volumes of liquid to the CSF inevitably raise the CSF pressure [a.k.a. intracranial pressure (ICP)], which may in turn lead to adverse reactions if the physiologically delimited threshold is exceeded. While long-term biological effects of elevated ICP (hydrocephalus) are known, the safety thresholds pertaining to short-term ICP elevations caused by IT administrations have not yet been characterized. This study aimed to investigate the dynamics of ICP in rats and non-human primates (NHPs) with respect to IT infusion rates and volumes. The safety regimes were estimated and analyzed across species to facilitate the development of translational large-volume IT therapies. The data revealed that the addition of a liquid to the CSF raised the ICP in a rate and volume-dependent manner. At low infusion rates (<0.12 ml/min in rats and <2 ml/min in NHPs), NHPs and rats displayed similar tolerance patterns. Specifically, safe accommodations of such added volumes were mainly facilitated by the accelerated pressure-dependent CSF drainage into the blood, with I stabilizing at different levels below the safety threshold of 28 ± 4 mm Hg in rats and 50 ± 5 mm Hg in NHPs. These ICPs were safely tolerated for extended durations (of at least 2–25 min). High infusion rates (including boluses) caused uncompensated exponential ICP elevations rapidly exceeding the safety thresholds. Their tolerance was species-dependent and was facilitated by the compensatory role of the varied components of craniospinal compliance while not excluding the possibility of other contributing factors. In conclusion, large volumes of liquids can safely be delivered via IT routes provided that ICP is monitored as a safety factor and cross-species physiological differences are accounted for.

scholarly journals Inflammation and Oxidative Stress: Potential Targets for Improving Prognosis After Subarachnoid Hemorrhage

2021 ◽  
Vol 15 ◽  
Author(s):  
Fan Wu ◽  
Zongchi Liu ◽  
Ganglei Li ◽  
Lihui Zhou ◽  
Kaiyuan Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Subarachnoid Hemorrhage ◽  
Immune Cells ◽  
Brain Dysfunction ◽  
New Ideas ◽  
Negative Role ◽  
The Central Nervous System ◽  
And Oxidative Stress

Subarachnoid hemorrhage (SAH) has a high mortality rate and causes long-term disability in many patients, often associated with cognitive impairment. However, the pathogenesis of delayed brain dysfunction after SAH is not fully understood. A growing body of evidence suggests that neuroinflammation and oxidative stress play a negative role in neurofunctional deficits. Red blood cells and hemoglobin, immune cells, proinflammatory cytokines, and peroxidases are directly or indirectly involved in the regulation of neuroinflammation and oxidative stress in the central nervous system after SAH. This review explores the role of various cellular and acellular components in secondary inflammation and oxidative stress after SAH, and aims to provide new ideas for clinical treatment to improve the prognosis of SAH.

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