scholarly journals Pharmacological and Biophysical Characteristics of Picrotoxin-Resistant, δSubunit-Containing GABAA Receptors

2021 ◽  
Vol 13 ◽  
Author(s):  
Hong-Jin Shu ◽  
Xinguo Lu ◽  
John Bracamontes ◽  
Joe Henry Steinbach ◽  
Charles F. Zorumski ◽  
...  

GABAA receptors (GABAARs) play a crucial role in inhibition in the central nervous system. GABAARs containing the δ subunit mediate tonic inhibition, have distinctive pharmacological properties and are associated with disorders of the nervous system. To explore this receptor sub-class, we recently developed mice with δ-containing receptors rendered resistant to the common non-competitive antagonist picrotoxin (PTX). Resistance was achieved with a knock-in point mutation (T269Y; T6’Y) in the mouse genome. Here we characterize pharmacological and biophysical features of GABAARs containing the mutated subunit to contextualize results from the KI mice. Recombinant receptors containing δ T6’Y plus WT α4 and WT β2 subunits exhibited 3-fold lower EC50 values for GABA but not THIP. GABA EC50 values in native receptors containing the mutated subunit were in the low micromolar range, in contrast with some published results that have suggested nM sensitivity of recombinant receptors. Rectification properties of δ-containing GABAARs were similar to γ2-containing receptors. Receptors containing δ T6’Y had marginally weaker sensitivity to positive allosteric modulators, likely a secondary consequence of differing GABA sensitivity. Overexpression of δT6’Y in neurons resulted in robust PTX-insensitive IPSCs, suggesting that δ-containing receptors are readily recruited by synaptically released GABA. Overall, our results give context to the use of δ receptors with the T6’Y mutation to explore the roles of δ-containing receptors in inhibition.

Author(s):  
Ezzatollah Keyhani

Acetylcholinesterase (EC 3.1.1.7) (ACHE) has been localized at cholinergic junctions both in the central nervous system and at the periphery and it functions in neurotransmission. ACHE was also found in other tissues without involvement in neurotransmission, but exhibiting the common property of transporting water and ions. This communication describes intracellular ACHE in mammalian bone marrow and its secretion into the extracellular medium.


Author(s):  
Anthony A. Paparo ◽  
Judith A. Murphy

The purpose of this study was to localize the red neuronal pigment in Mytilus edulis and examine its role in the control of lateral ciliary activity in the gill. The visceral ganglia (Vg) in the central nervous system show an over al red pigmentation. Most red pigments examined in squash preps and cryostat sec tions were localized in the neuronal cell bodies and proximal axon regions. Unstained cryostat sections showed highly localized patches of this pigment scattered throughout the cells in the form of dense granular masses about 5-7 um in diameter, with the individual granules ranging from 0.6-1.3 um in diame ter. Tissue stained with Gomori's method for Fe showed bright blue granular masses of about the same size and structure as previously seen in unstained cryostat sections.Thick section microanalysis (Fig.l) confirmed both the localization and presence of Fe in the nerve cell. These nerve cells of the Vg share with other pigmented photosensitive cells the common cytostructural feature of localization of absorbing molecules in intracellular organelles where they are tightly ordered in fine substructures.


1973 ◽  
Vol 71 (1-2) ◽  
pp. 1-8 ◽  
Author(s):  
Sylvio Celso Goncalves da Costa ◽  
Samuel B. Pessoa ◽  
Neize de Moura Pereira ◽  
Tania Colombo

The main object of the present paper is to furnish a brief account to the knowledgement of Protozoa parasitic in common Brazilian frog of the genus Leptodactylus for general students in Zoology and for investigators that use this frog as a laboratory animal. Hepatozoon leptodactyli (Haemogregarina leptodactyli) was found in two species of frogs - Leptodactylus ocellatus and L. pentadactylus - in which develop schizogony whereas sporogony occurs in the leech Haementeria lutzi as was obtainded in experimental conditions. Intracellular forms have been found in peripheral circulation, chiefly in erythrocytes, but we have found them in leukocytes too. Tissue stages were found in frog, liver, lungs, spleen, gut, brain and heart. The occurence of hemogregarine in the Central Nervous System was recorded by Costa & al,(13) and Ball (2). Some cytochemical methods were employed in attempt to differentiate gametocytes from trophozoites in the peripheral blood and to characterize the cystic membrane as well. The speorogonic cycle was developed in only one specie of leech. A brief description of the parasite is given.


Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1151-1161 ◽  
Author(s):  
Y. Zhang ◽  
A. Ungar ◽  
C. Fresquez ◽  
R. Holmgren

Previous studies have shown that the segment polarity locus gooseberry, which contains two closely related transcripts gooseberry-proximal and gooseberry-distal, is required for proper development in both the epidermis and the central nervous system of Drosophila. In this study, the roles of the gooseberry proteins in the process of cell fate specification have been examined by generating two fly lines in which either gooseberry-distal or gooseberry-proximal expression is under the control of an hsp70 promoter. We have found that ectopic expression of either gooseberry protein causes cell fate transformations that are reciprocal to those of a gooseberry deletion mutant. Our results suggest that the gooseberry-distal protein is required for the specification of naked cuticle in the epidermis and specific neuroblasts in the central nervous system. These roles may reflect independent functions in neuroblasts and epidermal cells or a single function in the common ectodermal precursor cells. The gooseberry-proximal protein is also found in the same neuroblasts as gooseberry-distal and in the descendants of these cells.


Author(s):  
Andrea C. Adams

Many immune-mediated diseases and infections affect the central and peripheral nervous systems. The common feature that characterizes both immune-mediated diseases and infections is a subacute temporal profile. Immune-mediated disease can affect only the nervous system or involve the nervous system as part of a systemic illness, as in vasculitis and connective tissue disease. Multiple sclerosis (MS), the most common disabling neurologic illness of young people, is the prototypical immune-mediated disease of the central nervous system (CNS).


Oncoreview ◽  
2016 ◽  
Vol 6 (4) ◽  
pp. 0-0 ◽  
Author(s):  
Łukasz Galus

Ifosfamide is a cytostatic drug commonly used in chemotherapy. One of the common adverse effects resulting from the treatment with ifosfamide is encephalopathy. This paper describes a case study of a 64-year-old patient who suffered from a full-blown encephalopathy as a result of chemotherapy administered during the treatment of fibrosarcoma of the femur. It provides a hypothesis of the mechanism behind toxic effects of ifosfamide on the central nervous system and elaborates on a number of documented ways of preventing aforementioned complications.


The cilia lining the stigmata of the branchial sac of an ascidian circulate water through the animal. These stigmatal cilia are under nervous control; when either siphon is stimulated, both siphons close by muscular contractions and at the same time the stigmatal cilia stop beating simultaneously in all parts of the branchial sac. Spontaneous ciliary arrests may also occur, with or without associated closure of the siphons. Elements of the branchial nervous system that run in the gill bars are assumed to be concerned in coordination of the ciliary arrests. The majority of the branchial nerve fibres emerge dorsally from the visceral nerves that form the posterior brain roots, although nerves are also believed to enter the branchial sac along its anterior margin. No cell bodies could be found in the branchial nerves or in the visceral nerves, so that the cell bodies of the branchial nerve fibres are assumed to lie in the central nervous system. The branchial nerve fibres form a peripheral conducting net extending throughout the branchial sac. Branches of these nerve fibres terminate in contact with some of the ciliated cells; cell-to-cell conduction (through close junctions?) probably spreads excitation to the other ciliated cells. Nerve-nerve junctions appear to be more sensitive to curare than those between nerves and ciliated cells. Electrical recordings from the branchial sac, obtained with suction electrodes, show that arrest of the cilia is accompanied by electrical activity, and that prolonged arrest is maintained by trains of regular pulses. Intracellular microelectrodes in the ciliated cells indicate that these cells have a negative resting potential of 30-40 mV, and that a ciliary arrest is associated with a positive-going spike of 45-50 mV. The externally recorded ‘ciliary arrest potentials’ probably represent the coordinated depolarization of many ciliated cells. The rhythmical character of the trains of pulses presumably depends on pacemaker activity; this is not localized, since intact organisms or isolated small portions of the branchial sac are capable of generating similar trains of pulses. During the arrest response the stigmatal cilia first perform a reverse beat, then maintain the reverse position for several seconds before slowly relaxing and after several more seconds recommencing to beat with progressively increasing amplitude. The duration of the arrest response varies in media with different concentrations of the common cations, and also varies in response to repetitive stimulation, in a manner which suggests that the depolarization of the ciliated cells is associated with an influx of Ca 2+ , so that the ciliary control here may have some close parallels with that described for Paramecium .


2020 ◽  
Author(s):  
Shahrzad Nazari ◽  
Amirhossein Azari Jafari ◽  
Seyyedmohammadsadeq Mirmoeeni ◽  
Saeid Sadeghian ◽  
Mohammad Eghbal Heidari ◽  
...  

Background: At the end of December 2019, a novel respiratory infection, initially reported in China, known as COVID-19 initially reported in China, and later known as COVID-19, led to a global pandemic. Despite many studies reporting respiratory infections as the primary manifestations of this illness, an increasing number of investigations have focused on the central nervous system (CNS) manifestations in COVID-19. In this study, we aimed to evaluate the CNS presentations in COVID-19 patients in an attempt to identify the common CNS features and provide a better overview to tackle this new pandemic. Methods: In this systematic review and meta-analysis, we searched PubMed, Web of Science, Ovid, Embase, Scopus, and Google Scholar. Included studies were publications that reported the CNS features between January 1st, 2020, to April 20th, 2020. The data of selected studies were screened and extracted independently by four reviewers. Extracted data analyzed by using STATA statistical software. The study protocol registered with PROSPERO (CRD42020184456). Results: Of 2353 retrieved studies, we selected 64 studies with 11282 patients after screening. Most of the studies were conducted in China (58 studies). The most common CNS symptom of COVID-19 were Headache (8.69%, 95%CI: 6.76%-10.82%), Dizziness (5.94%, 95%CI: 3.66%-8.22%), and Impaired consciousness (1.9%, 95%CI: 1%-2.79%). Conclusions: The growing number of studies have reported COVID-19, CNS presentations as remarkable manifestations that happen. Hence, understanding the CNS characteristics of COVID-19 can help us for better diagnosis and ultimately prevention of worse outcomes.


1919 ◽  
Vol 2 (1) ◽  
pp. 73-85 ◽  
Author(s):  
J. F. Gaskell

1. The sympathetic nervous system and the adjuvant adrenalin-secreting system are found in their earliest form in the annelid kingdom, and consist of cells situated in the central nervous system which are the common ancestors of both, and which are both secretory and nervous in function. 2. These cells are developed in the annelid kingdom parallel with the development of a contractile vascular system, which possesses muscles comparable in physiological actions with the muscle of the vertebrate heart. 3. This vascular muscle is regulated by the processes of the common ancestral cells as well as by their secretory activity. 4. In the primitive form contractile rhythm is an intrinsic property of cardiac muscle; its nerve supply regulates the rhythm, it does not initiate it. The beat is therefore myogenic, not neurogenic. 5. The contractile vascular system of annelids is mainly branchial in function. The vertebrate heart has been derived from it by the growing around of the lateral body folds to form a new ventral surface.


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