scholarly journals Morphological and Calcium Signaling Alterations of Neuroglial Cells in Cerebellar Cortical Dysplasia Induced by Carmustine

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1581
Author(s):  
Cynthia Alejandra Rodríguez-Arzate ◽  
Marianne Lizeth Martínez-Mendoza ◽  
Israel Rocha-Mendoza ◽  
Yryx Luna-Palacios ◽  
Jacob Licea-Rodríguez ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Brain Cortex ◽  
Motor Coordination ◽  
Cortical Dysplasia ◽  
Experimental Models ◽  
Glutamatergic Transmission ◽  
Intracellular Calcium Dynamics ◽  
Cortical Dysplasias ◽  
The Brain

Cortical dysplasias are alterations in the organization of the layers of the brain cortex due to problems in neuronal migration during development. The neuronal component has been widely studied in experimental models of cortical dysplasias. In contrast, little is known about how glia are affected. In the cerebellum, Bergmann glia (BG) are essential for neuronal migration during development, and in adult they mediate the control of fine movements through glutamatergic transmission. The aim of this study was to characterize the morphology and intracellular calcium dynamics of BG and astrocytes from mouse cerebellum and their modifications in a model of cortical dysplasia induced by carmustine (BCNU). Carmustine-treated mice were affected in their motor coordination and balance. Cerebellar dysplasias and heterotopias were more frequently found in lobule X. Morphology of BG cells and astrocytes was affected, as were their spontaneous [Ca2+]i transients in slice preparation and in vitro.

scholarly journals ANTI-PSYCHOTIC ACTIVITY OF PYRUS COMMUNIS JUICE

2017 ◽  
Vol 9 (4) ◽  
pp. 113
Author(s):  
Arzoo Singh Pannu ◽  
Milind Parle
Keyword(s):  
Experimental Models ◽  
Pyrus Communis ◽  
Anti Psychotic ◽  
Head Bobbing ◽  
Stereotypic Behaviour ◽  
Biochemical Estimation ◽  
Pear Juice ◽  
The Brain ◽  
Grooming Behaviour

Objective: The present study aim to investigate the anti-psychotic potential of pyrus communis in the rodents.Methods: The fresh juice of pyrus communis (Pear) was administered orally to rodents for 21 d and the anti-psychotic activity was assessed by in vitro methods viz ketamine induced stereotypic behaviour, pole climbing avoidance in rats and swim induced grooming behaviour experimental models. The biochemical estimation was done on 21 d.Results: The different concentrations of fresh pyrus communis juice was assayed. When pyrus communis juice (PCJ) was administered chronically for 21 d remarkably decreased ketamine induced falling, head-bobbing, weaving and turning counts. Administration of Pear juice significantly delayed the latency time taken by the animals to climb the pole in Cook’s pole climb apparatus. In swim induced grooming behaviour model, Pear juice significantly reduced swim induced grooming behaviour. Moreover, Pear juice significantly decreased the brain dopamine levels and inhibited acetyl cholinesterase activity. In the present study, Pear juice significantly enhanced reduced glutathione levels in the brains of mice, thereby reflecting enhanced scavenging of free radicals and in turn preventing occurrence of psychotic attack.Conclusion: The present study revealed that pyrus communis juice possessed significant anti-psychotic activity.

scholarly journals Scapinin-induced Inhibition of Axon Elongation Is Attenuated by Phosphorylation and Translocation to the Cytoplasm

2011 ◽  
Vol 286 (22) ◽  
pp. 19724-19734 ◽  
Author(s):  
Hovik Farghaian ◽  
Yu Chen ◽  
Ada W. Y. Fu ◽  
Amy K. Y. Fu ◽  
Jacque P. K. Ip ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Brain Cortex ◽  
Inhibitory Effect ◽  
Adult Brain ◽  
Actin Binding ◽  
Mutant Form ◽  
Axon Elongation ◽  
Rat Cortical Neurons ◽  
The Brain

Scapinin is an actin- and PP1-binding protein that is exclusively expressed in the brain; however, its function in neurons has not been investigated. Here we show that expression of scapinin in primary rat cortical neurons inhibits axon elongation without affecting axon branching, dendritic outgrowth, or polarity. This inhibitory effect was dependent on its ability to bind actin because a mutant form that does not bind actin had no effect on axon elongation. Immunofluorescence analysis showed that scapinin is predominantly located in the distal axon shaft, cell body, and nucleus of neurons and displays a reciprocal staining pattern to phalloidin, consistent with previous reports that it binds actin monomers to inhibit polymerization. We show that scapinin is phosphorylated at a highly conserved site in the central region of the protein (Ser-277) by Cdk5 in vitro. Expression of a scapinin phospho-mimetic mutant (S277D) restored normal axon elongation without affecting actin binding. Instead, phosphorylated scapinin was sequestered in the cytoplasm of neurons and away from the axon. Because its expression is highest in relatively plastic regions of the adult brain (cortex, hippocampus), scapinin is a new regulator of neurite outgrowth and neuroplasticity in the brain.

BIOCHEMICAL STUDIES ON CHLORPROMAZINE: 1. THE EFFECT OF CHLORPROMAZINE ON RESPIRATORY ACTIVITY OF ISOLATED RAT BRAIN CORTEX

1957 ◽  
Vol 35 (12) ◽  
pp. 1135-1144 ◽  
Author(s):  
O. Lindan ◽  
J. H. Quastel ◽  
S. Sved
Keyword(s):  
Plasma Proteins ◽  
Brain Cortex ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Acid Dyes ◽  
Highly Sensitive ◽  
Binding Power ◽  
The Brain

Chlorpromazine exerts a progressive inhibitory activity (at 0.3–0.6 mM) on the respiration of brain cortex in presence of either glucose, fructose, pyruvate, or L-glutamate. A similar progressive inhibition occurs with other phenothiazine derivatives such as methylene blue and phenergan. However, chlorpromazine does not inhibit oxygen uptake in the presence of succinate. Potassium-stimulated respiration is highly sensitive to chlorpromazine, as it is markedly diminished by 0.2 mM concentration of the drug, a concentration which does not affect the unstimulated respiration. The increased inhibition of potassium-stimulated respiration is only clearly seen during the early part of the experiment.Chlorpromazine is bound by tissue constituents. At a constant concentration of chlorpromazine (0.6 mM), its inhibitory effect on cortical respiration may be abolished by markedly increasing the amount of tissue present. The inhibitory effect of chlorpromazine may be diminished by addition of plasma proteins (αβ-globulin) or by addition of heated homogenized brain, liver, or kidney. No binding occurs with polyglutamic acid, ribonucleic, and deoxyribonucleic acids, but binding does occur with certain acid dyes such as trypan red. Trypan red may be used to immobilize free chlorpromazine. When the latter drug is absorbed, however, by the nervous tissue, the addition of trypan red has no effect on the metabolic inhibitions brought about by the absorbed chlorpromazine.It is concluded that chlorpromazine resembles a large variety of narcotics and anaesthetics in its marked inhibitory effects on potassium-stimulated respiration of the brain. Its action, in vitro, however, differs from that of the narcotics in bringing about progressive, apparently irreversible, inhibitions and in its high binding power with tissue proteins. Such apparently irreversible inhibition is consistent with the conclusion that the drug, after combination with the tissue, gradually diffuses into the cell bringing about metabolic inhibitions.

scholarly journals In vitro Modeling of Prion Strain Tropism

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 236
Author(s):  
Etienne Levavasseur ◽  
Nicolas Privat ◽  
Stéphane Haïk
Keyword(s):  
Protein Misfolding ◽  
Genetic Material ◽  
Brain Regions ◽  
Experimental Models ◽  
Neuronal Cultures ◽  
Infectious Agents ◽  
Prion Strain ◽  
Specific Targeting ◽  
The Brain

Prions are atypical infectious agents lacking genetic material. Yet, various strains have been isolated from animals and humans using experimental models. They are distinguished by the resulting pattern of disease, including the localization of PrPsc deposits and the spongiform changes they induce in the brain of affected individuals. In this paper, we discuss the emerging use of cellular and acellular models to decipher the mechanisms involved in the strain-specific targeting of distinct brain regions. Recent studies suggest that neuronal cultures, protein misfolding cyclic amplification, and combination of both approaches may be useful to explore this under-investigated but central domain of the prion field.

scholarly journals Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jasmin Morandell ◽  
Lena A. Schwarz ◽  
Bernadette Basilico ◽  
Saren Tasciyan ◽  
Georgi Dimchev ◽  
...  
Keyword(s):  
Cell Migration ◽  
Transcriptional Activation ◽  
Neuronal Migration ◽  
Motor Coordination ◽  
De Novo ◽  
Autism Spectrum ◽  
Loss Of Function ◽  
Critical Window ◽  
Cytoskeleton Organization

AbstractDe novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). In mouse, constitutive Cul3 haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs.

scholarly journals From Neural Stem Cells (NSC) to Glioblastoma (GBM): A Natural History of GBM Recapitulated in Vitro

2020 ◽  
Author(s):  
Cristina Almengló ◽  
Pilar Caamaño ◽  
Máximo Fraga ◽  
Jesús Devesa ◽  
José A. Costoya ◽  
...  
Keyword(s):  
Stem Cells ◽  
Natural History ◽  
Therapeutic Strategies ◽  
Experimental Models ◽  
Oncogenic Transformation ◽  
Primary Brain Tumour ◽  
Primary Mouse ◽  
History Of ◽  
The Brain

Due to its aggressive and invasive nature glioblastoma (GBM), the most common and aggressive primary brain tumour in adults, remains almost invariably lethal. Significant advances in the last several years have elucidated much of the molecular and genetic complexities of GBM. However, GBM exhibits a vast genetic variation and a wide diversity of phenotypes that has complicated the development of effective therapeutic strategies. This complex pathogenesis makes it necessary the development of experimental models that could be used to further understand the disease, and also to provide a more realistic testing ground for potential therapies. In this report, we describe the process of transformation of primary mouse embryo astrocytes into immortalized cultures with neural stem cell characteristics, that are able to generate of GBM when injected in the brain of C57BL/6 mice, or heterotopic tumours when injected iv. Overall, our results show that oncogenic transformation is a fate for NSC if cultured for long periods in vitro. In addition, since no additional hit is necessary to induce the oncogenic transformation, our model may be used to investigate the pathogenesis of gliomagenesis and to test the effectiveness of different drugs throughout the natural history of GBM.

scholarly journals Features of Borna disease virus reproduction in brain cells and laboratory diagnosis of infection

2019 ◽  
Vol 2019 (2) ◽  
pp. 21-24
Author(s):  
Константин Юров ◽  
Konstantin Yurov ◽  
Светлана Алексеенкова ◽  
Svetlana Alekseenkova
Keyword(s):  
Disease Virus ◽  
Present Report ◽  
Retrograde Transport ◽  
Laboratory Diagnosis ◽  
Experimental Models ◽  
Brain Cells ◽  
Borna Disease Virus ◽  
The Brain ◽  
Borna Disease

The Borna Disease Virus (BDV) is a non-segmented RNA-containing virus belonging to the Bornaviridae family. The pathogen causes progressive meningoencephalitis in animals of various types. Despite numerous studies, some stages of reproduction of Bornavirus remain poorly understood, in particular, receptor-mediated penetration, retrograde transport into the nucleus, assembly and release of the virion, etc. The present report presents the results of demonstrating studies that were aimed at following the immunoenzyme method, the distribution of the main protein BDV ― phosphoprotein P (p24) in the brain cells of naturally susceptible animals, compare nnye data with the results of a number of authors, made mainly in experimental models. Microscopic examination of histological sections of the brain tissue of horses and sheep treated with specific serum against p24 BDV in a light or luminescent microscope observed a specific color in the form of: small granules; diffuse fluorescence of the cytoplasm; larger granules, apparently due to aggregation of endosomes, for axon transportation; formations in the form of beads, demonstrating the transport of viral material along the axon. In vitro results were obtained indicating that it is possible to transport RNPs via a short path through cytoplasmic bridges. The presented results will allow a better understanding of the neuropathogenesis of Born's disease and improve the diagnosis of the disease.

Serotonin 5HT1B/1D Receptor Agonists Abolish NMDA Receptor-evoked Enhancement of Nitric Oxide Synthase Activity and cGMP Concentration in Brain Cortex Slices

Cephalalgia ◽  
1999 ◽  
Vol 19 (10) ◽  
pp. 859-865 ◽  
Author(s):  
A Stȩpień ◽  
M Chalimoniuk ◽  
J Strosznajder
Keyword(s):  
Nmda Receptor ◽  
Brain Cortex ◽  
Receptor Agonists ◽  
Adult Rat ◽  
Adult Rat Brain ◽  
Brain Cortex Slices ◽  
Cortex Slices ◽  
The Brain

Our previous studies indicating that the function of excitatory amino acids, NMDA type receptor, is modulated by serotonin focused on the interaction between serotonin 5HT1B/1D and glutamate, NMDA receptor in brain cortex. The effect of agonists of 5HT1B/1D receptor, sumatriptan, and zolmitriptan on NMDA receptor-evoked activation of nitric oxide (NO) and cGMP synthesis in adult rat brain cortex slices was investigated. Two kinds of experiment were carried out using adult rats. In one of them, sumatriptan or zolmitriptan was administered in vivo subcutaneously (s.c.) in a dose of 0.1 mg per kg body weight. Brain slices were then prepared and used in the experiments or, in the other exclusively in vitro studies, both agonists at 10 μM concentration were added directly to the incubation medium containing adult rat brain cortex slices. The data obtained from these studies indicated that stimulation of NMDA receptor in brain cortex slices. The data obtained from these studies indicated that stimulation of NMDA receptor in brain cortex slices leads to a large increase in calcium, calmodulin-dependent NO synthase (NOS) activity and to significant enhancement of the cGMP level. This NMDA receptor-dependent NO and cGMP release was completely blocked by competitive and noncompetitive NMDA receptor antagonists APV (10 μM) or MK-801 (10 μM.), respectively. The specific inhibitor of Ca2+-dependent isoforms of NOS (N-nitro-1-arginine NNLA and 7-nitroindozole (7-N1)) eliminated the NMDA receptor-mediated enhancement of NO and cGMP release. Moreover, the serotonin 5HT1B/1D receptor agonists sumatriptan and zolmitriptan administrated in vivo (s.c.) or in vitro abolished NMDA receptor-evoked NO signalling in brain cortex. The potency of both agonists investigated directly in vitro was similar to their effect after in vivo administration. These results suggest that both serotonin 5HT1B/1D receptor agonists may play an important role in modulating the NO and cGMP-dependent signal transduction pathway in the brain. This effect of sumatriptan and zolmitriptan on NO signaling in the brain system should be taken into consideration when investigating their mechanism of action in the migraine attack.

Correlated in vivo 31P-NMR and NADH fluorometric studies on gerbil brain in graded hypoxia and hyperoxia

1988 ◽  
Vol 254 (5) ◽  
pp. C699-C708 ◽  
Author(s):  
L. Gyulai ◽  
B. Chance ◽  
L. Ligeti ◽  
G. McDonald ◽  
J. Cone
Keyword(s):  
Brain Cortex ◽  
31P Nmr ◽  
Energy Coupling ◽  
Gerbil Brain ◽  
Mitochondrial Redox State ◽  
Redox Change ◽  
The Relationship ◽  
The Brain

Mitochondrial energy coupling in the gerbil brain was characterized by the relationship between intracellular phosphocreatine (PCr)/inorganic phosphate (Pi), phosphorylation ratio, and the mitochondrial redox state in graded hypoxia. Phosphorus-nuclear magnetic resonance (NMR) spectra of the brain and whole head were taken by surface and saddle coil, respectively. The NADH level of the brain cortex was monitored by in vivo fluororeflectometry. The PCr and Pi of the head and brain did not change between 100 and 10% O2 inhalation. PCr progressively decreased and Pi progressively increased with 6 and 4% 0% inhalation in the head. The PCr/Pi of the brain decreased by 44% at 6% fraction of inhaled oxygen (FIO2) and 57% at 4% FIO2. The ATP level did not change during hypoxia. The calculated phosphorylation ratio of the brain ([PCr] Kck[H+]/[Cr][Pi]) = ([ATP]/[ADP][Pi]) was 4.1 X 10(4) M-1 in normoxia. Hypoxia of increasing severity induced increasing NAD reduction of the brain cortex with 17% NAD reduction at 10% FIO2 when there was no change in phosphorylation ratio. The phosphorylation ratio decreased, i.e., the mitochondria failed to maintain the energy level of the brain when the magnitude of the change in NAD reduction to hypoxia was half of the total redox change between hyperoxia and anoxia. These studies demonstrated the feasibility of combined 31P-NMR and NADH fluorometry measurements on brain in vivo. The observations show similarities between the responses of mitochondrial oxidative phosphorylation to hypoxia in vivo and in vitro.

BIOCHEMICAL STUDIES ON CHLORPROMAZINE: 1. THE EFFECT OF CHLORPROMAZINE ON RESPIRATORY ACTIVITY OF ISOLATED RAT BRAIN CORTEX

1957 ◽  
Vol 35 (1) ◽  
pp. 1135-1144 ◽  
Author(s):  
O. Lindan ◽  
J. H. Quastel ◽  
S. Sved
Keyword(s):  
Plasma Proteins ◽  
Brain Cortex ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Acid Dyes ◽  
Highly Sensitive ◽  
Binding Power ◽  
The Brain

Chlorpromazine exerts a progressive inhibitory activity (at 0.3–0.6 mM) on the respiration of brain cortex in presence of either glucose, fructose, pyruvate, or L-glutamate. A similar progressive inhibition occurs with other phenothiazine derivatives such as methylene blue and phenergan. However, chlorpromazine does not inhibit oxygen uptake in the presence of succinate. Potassium-stimulated respiration is highly sensitive to chlorpromazine, as it is markedly diminished by 0.2 mM concentration of the drug, a concentration which does not affect the unstimulated respiration. The increased inhibition of potassium-stimulated respiration is only clearly seen during the early part of the experiment.Chlorpromazine is bound by tissue constituents. At a constant concentration of chlorpromazine (0.6 mM), its inhibitory effect on cortical respiration may be abolished by markedly increasing the amount of tissue present. The inhibitory effect of chlorpromazine may be diminished by addition of plasma proteins (αβ-globulin) or by addition of heated homogenized brain, liver, or kidney. No binding occurs with polyglutamic acid, ribonucleic, and deoxyribonucleic acids, but binding does occur with certain acid dyes such as trypan red. Trypan red may be used to immobilize free chlorpromazine. When the latter drug is absorbed, however, by the nervous tissue, the addition of trypan red has no effect on the metabolic inhibitions brought about by the absorbed chlorpromazine.It is concluded that chlorpromazine resembles a large variety of narcotics and anaesthetics in its marked inhibitory effects on potassium-stimulated respiration of the brain. Its action, in vitro, however, differs from that of the narcotics in bringing about progressive, apparently irreversible, inhibitions and in its high binding power with tissue proteins. Such apparently irreversible inhibition is consistent with the conclusion that the drug, after combination with the tissue, gradually diffuses into the cell bringing about metabolic inhibitions.

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