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1.
Toxicol Ind Health ; 39(3): 127-137, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36680355

RESUMEN

Zinc oxide nanoparticles (ZnO NP) are commonly used engineered NPs with extensive usage in consumer products, thus leading to direct exposure to humans. The direct route of exposure is through inhalation. Once inhaled, these particles accumulate in the lungs, increasing the chances of respiratory tract illness through cellular organelle damage. Zinc oxide nanoparticle-treated lung cells are reported to display cytotoxicity, increase DNA damage, and induce oxidative stress. The current study focused on the effects of ZnO NPs on mitochondrial dynamics (fission and fusion) in human lung epithelial cells (A549). The lung cells were exposed to ZnO NPs at 50 and 100 µg/ml concentrations, and their mitochondrial dynamics were assessed to understand the effects of the NPs. Treatment with ZnO NPs reduced the activity of mitochondrial complex I and complex III and altered mitochondrial structural and functional characteristics in a concentration-dependent manner. Zinc oxide nanoparticles exposure showed an increase in small and round-shaped mitochondria. The expression of various fission proteins (Drp1 and Fis1) and fusion proteins (Mfn1, Mfn2, and OPA1) was altered upon exposure to ZnO NPs. Our studies showed dysfunction of the mitochondria induced by ZnO NPs. In fibroblast mitochondrial dynamics, fission symbolizes threshold damage. In this paper, we have shown that the mitochondrial fission phenotype increased upon exposure to ZnO NPs. The paper emphasizes that these particles enter mitochondria, triggering a stress response that results in the removal of mitochondria via fission. It provides relevant data for safety guidelines to ensure the safer use of these particles.


Asunto(s)
Nanopartículas , Óxido de Zinc , Humanos , Óxido de Zinc/toxicidad , Células Epiteliales Alveolares , Especies Reactivas de Oxígeno/metabolismo , Nanopartículas/toxicidad , Mitocondrias
2.
J Cell Physiol ; 236(9): 6754-6771, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33788269

RESUMEN

Hypobaric hypoxia at higher altitudes usually impairs cognitive function. Previous studies suggested that epigenetic modifications are the culprits for this condition. Here, we set out to determine how hypobaric hypoxia mediates epigenetic modifications and how this condition worsens neurodegeneration and memory loss in rats. In the current study, different duration of hypobaric hypoxia exposure showed a discrete pattern of histone acetyltransferases and histone deacetylases (HDACs) gene expression in the hippocampus when compared with control rat brains. The level of acetylation sites in histone H2A, H3 and H4 was significantly decreased under hypobaric hypoxia exposure compared to the control rat's hippocampus. Additionally, inhibiting the HDAC family with sodium butyrate administration (1.2 g/kg body weight) attenuated neurodegeneration and memory loss in hypobaric hypoxia-exposed rats. Moreover, histone acetylation increased at the promoter regions of brain-derived neurotrophic factor (BDNF); thereby its protein expression was enhanced significantly in hypobaric hypoxia exposed rats treated with HDAC inhibitor compared with hypoxic rats. Thus, BDNF expression upregulated cAMP-response element binding protein (CREB) phosphorylation by stimulation of PI3K/GSK3ß/CREB axis, which counteracts hypobaric hypoxia-induced spatial memory impairment. In conclusion, these results suggested that sodium butyrate is a novel therapeutic agent for the treatment of spatial memory loss associated with hypobaric hypoxia, and also further studies are warranted to explore specific HDAC inhibitors in this condition.


Asunto(s)
Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Hipoxia/complicaciones , Trastornos de la Memoria/etiología , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Memoria Espacial , Acetilación/efectos de los fármacos , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Hipocampo/metabolismo , Histona Acetiltransferasas/genética , Histona Acetiltransferasas/metabolismo , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Histonas/metabolismo , Masculino , Trastornos de la Memoria/metabolismo , Modelos Biológicos , Degeneración Nerviosa/complicaciones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuroprotección/efectos de los fármacos , Regiones Promotoras Genéticas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Memoria Espacial/efectos de los fármacos
3.
Exp Brain Res ; 239(6): 1747-1763, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33779792

RESUMEN

Professionals and mountaineers often face the problem of reperfusion injury due to re-oxygenation, upon their return to sea-level after sojourn at high altitude. Small conductance calcium-activated potassium channels (SK channels) have a role in regulating hippocampal synaptic plasticity. However, the role of SK channels under hypoxia-reoxygenation (H/R) is unknown. The present study hypothesized that SK channels play a significant role in H/R induced cognitive dysfunction. Sprague-Dawley rats were exposed to simulated HH (25,000 ft) continuously for 7 days followed by reoxygenation periods 3, 6, 24, 48, 72 and 120 h. It was observed that H/R exposure caused impairment in spatial memory as indicated by increased latency (p < 0.001) and pathlength (p < 0.001). The SK1 channel expression increased upon HH exposure (102.89 ± 7.055), which abrogated upon reoxygenation. HH exposure results in an increase in SK2 (CA3, 297.67 ± 6.69) and SK3 (CA1, 246 ± 5.13) channels which continued to increase gradually upon reoxygenation. The number of pyknotic cells (24 ± 2.03) (p < 0.01) and the expression of caspase-3 increased with HH exposure, which continued in the reoxygenation group (177.795 ± 1.264). Similar pattern was observed in lipid peroxidation (p < 0.001), LDH activity (p < 0.001) and ROS production (p < 0.001). A positive correlation of memory, cell death and oxidative stress indicates that H/R exposure increases oxidative stress coupled with SK channel expression, which may play a role in H/R-induced cognitive decline and neurodegeneration.


Asunto(s)
Hipocampo , Trastornos de la Memoria , Animales , Hipoxia , Trastornos de la Memoria/etiología , Ratas , Ratas Sprague-Dawley , Memoria Espacial
4.
Brain Behav Immun ; 82: 129-144, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31408672

RESUMEN

BACKGROUND: An association between neuroinflammation, reduced adult neurogenesis, and cognitive impairment has been established in sleep deprivation (SD). Complement receptors are expressed on neuronal and glial cells, thus, regulate the neuroinflammation, neurogenesis and learning/memory. However, understanding of the effect of SD on the brain-immune system interaction associated with cognitive dysfunction and its mechanisms is obscure. We hypothesized that complement activation induced changes in inflammatory and neurogenesis related proteins might be involved in the cognitive impairment during SD. METHODOLOGY: Adult male Sprague Dawley rats were used. Rats were sleep deprived for 48 h using a novel automated SD apparatus. Dosage of BrdU (50 mg/kg/day, i.p. in 0.07 N NaOH), complement C3a receptor antagonist (C3aRA; SB290157; 1 mg/kg/day, i.p.) in 1.16% v/v PBS and complement C5a receptor antagonist (C5aRA; W-54011; 1 mg/kg/day, i.p.) in normal saline were used. Rats were subjected to spatial memory evaluation following SD. Hippocampal tissue was collected for biochemical, molecular, and immunohistochemical studies. T-test and ANOVA were used for the statistical analysis. RESULTS: An up-regulation in the levels of complement components (C3, C5, C3a, C5a) and receptors (C3aR and C5aR) in hippocampus, displayed the complement activation during SD. Selective antagonism of C3aR/C5aR improved the spatial memory performance of sleep-deprived rats. C3aR antagonist (C3aRA) or C5aR antagonist (C5aRA) treatment inhibited the gliosis, maintained inflammatory cytokines balance in hippocampus during SD. Complement C3aR/C5aR antagonism improved hippocampal adult neurogenesis via up-regulating the BDNF level following SD. Administration of C3aRA and C5aRA significantly maintained synaptic homeostasis in hippocampus after SD. Gene expression analysis showed down-regulation in the mRNA levels of signal transduction pathways (Notch and Wnt), differentiation and axogenous proteins, which were found to be improved after C3aRA/C5aRA treatment. These findings were validated at protein and cellular level. Changes in the corticosterone level and ATP-adenosine-NO pathway were established as the key mechanisms underlying complement activation mediated consequences of SD. CONCLUSION: Our study suggests complement (C3a-C3aR and C5a-C5aR) activation as the novel mechanism underlying spatial memory impairment via promoting neuroinflammation and adult neurogenesis decline in hippocampus during SD, thereby, complement (C3aR/C5aR) antagonist may serve as the novel therapeutics to improve the SD mediated consequences.


Asunto(s)
Activación de Complemento/inmunología , Neuroinmunomodulación/fisiología , Privación de Sueño/metabolismo , Animales , Arginina/análogos & derivados , Arginina/farmacología , Compuestos de Bencidrilo/farmacología , Disfunción Cognitiva/inmunología , Disfunción Cognitiva/metabolismo , Activación de Complemento/fisiología , Complemento C3a/metabolismo , Hipocampo/metabolismo , Masculino , Neurogénesis/inmunología , Neurogénesis/fisiología , Neuroinmunomodulación/inmunología , Neuronas/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Complemento/metabolismo , Transducción de Señal/fisiología , Privación de Sueño/inmunología , Memoria Espacial/fisiología , Lóbulo Temporal/metabolismo
6.
ACS Chem Neurosci ; 15(6): 1084-1095, 2024 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-38462729

RESUMEN

People travel to high-altitude regions as tourists, workers, and military personnel on duty. Despite the consistent 21% oxygen content in the atmosphere, ascending to higher altitudes results in a decrease in the partial pressure of oxygen, inducing a state known as hypobaric hypoxia (HH). HH is an environmental stress that is responsible for neuroinflammation and behavioral deficits (anxiety, depression, mood disturbance, etc.), but little is known about its metabolic pathways. The kynurenine pathway (KP) is a promising candidate to uncover the mysteries of HH stress, as it is an important regulator of the immune system and is associated with behavioral deficits. To investigate the role of KP under HH, the levels of KP metabolites in the serum, cerebrospinal fluid (CSF), and brain tissue (prefrontal cortex-PFC, neocortex, and hippocampus) of male Sprague-Dawley rats exposed to HH at 7620 m for 1, 3, and 7 days were estimated utilizing high-performance liquid chromatography (HPLC). The behavioral analogs for anxiety-like and depression-like behavior were assessed using the open field test and forced swim test, respectively. Upon HH exposure, crosstalk between the periphery and central nervous system and KP metabolite region-dependent differential expression in the brain were observed. KP metabolites showed a positive correlation with behavioral parameters. The results of our study are indicative that KP can be proposed as the etiology of behavioral deficits, and KP metabolite levels in serum or CSF can be used as plausible markers for anxiety-like and depression-like behaviors under HH stress with a scope of targeted therapeutic interventions.


Asunto(s)
Hipoxia , Quinurenina , Humanos , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Hipoxia/metabolismo , Hipocampo/metabolismo , Oxígeno/metabolismo
7.
Chem Biol Interact ; 369: 110284, 2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36462549

RESUMEN

ZnO nanoparticles (ZnO NPs) are widely used engineered nanomaterials. Due to induced genotoxicity, increased oxidative stress, and teratogenicity, these NPs have been reported to be toxic. In the present study, we emphasise the role of vital proteins in regulating ZnO NP-induced abnormal phenotypes, particularly the deformed thorax and single wing in the Drosophila melanogaster progeny fed on 0.1-10 mM ZnO NPs. To understand how protein expression regulates this particular phenotype on ZnO NPs exposure, toxicoproteomics profile of control and abnormal phenotype flies was generated using LC/MS/MS. Gene ontology enrichment studies of proteomics data were carried out using CLUEGO and STRAP software. The bioinformatics tool STRING was used to generate a protein-protein interaction map of key proteins of enrichment analysis. Following ZnO NP exposure, the differential expression of key proteins of the Wnt pathway was prominent. Altered expression of various proteins of the Wnt pathway (CaMKII), cytoskeleton (Actin), and calponin resulted in developmental defects in drosophila progeny. In addition, immunohistology studies showed a significant deviation in the expression of wingless protein of ZnO NPs treated larvae in comparison to control. According to these findings, the interaction of the wnt pathway and cytoskeletal proteins with ZnO NPs caused developmental abnormalities in the subsequent generation of drosophila, highlighting the transgenerational toxic effects of these nanoparticles.


Asunto(s)
Óxido de Zinc , Animales , Óxido de Zinc/toxicidad , Drosophila , Vía de Señalización Wnt , Drosophila melanogaster , Espectrometría de Masas en Tándem , Estrés Oxidativo , Proteínas del Citoesqueleto , Citoesqueleto , Calponinas
8.
Cell Mol Neurobiol ; 32(4): 599-611, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22331403

RESUMEN

Hypobaric hypoxia (HH) induced neurodegeneration has been attributed to several factors including increased oxidative stress, glutamate excitotoxicity, decreased growth factors, apoptosis, etc. Though enriched environment (EE) has been known to have beneficial effects in various neurological disorders, its effect on HH mediated neurodegeneration remains to be studied. Therefore, the present study was conducted to explore the effect of EE on HH induced neurodegeneration. Male Sprague-Dawley rats were placed in enriched and standard conditions during exposure to HH (7 days) equivalent to an altitude of 25,000 ft. The effect of EE on oxidative stress markers, apoptosis, and corticosterone level in hippocampus was investigated. EE during exposure to HH was found to decrease neurodegeneration as evident from decreased caspase 3 expression and LDH leakage. However, no significant changes were observed in ROS, MDA, and antioxidant status of hippocampus. HH elevates corticosterone level and affected the diurnal corticoid rhythm which may contribute to neurodegeneration, whereas EE ameliorate this effect. Because of the association of neurotrophins and stress and/or corticosterone the BDNF and NGF levels were also examined and it was found that HH decreases their level but concurrent exposure to EE maintains their level. Moreover, inhibition of Tyrosine kinase receptor (Trk) with K252a nullifies the protective effect of EE, whereas Trk activation with agonist, amitriptyline showed protective effect similar to EE. Taken together, we conclude that EE has a potential to ameliorate HH mediated neuronal degeneration which may act through antioxidant independent pathway by modulation of neurotrophins.


Asunto(s)
Antioxidantes/metabolismo , Ambiente , Hipoxia Encefálica/prevención & control , Degeneración Nerviosa/prevención & control , Estrés Oxidativo/fisiología , Transducción de Señal/fisiología , Animales , Cámaras de Exposición Atmosférica/efectos adversos , Hipocampo/metabolismo , Hipocampo/patología , Hipoxia Encefálica/metabolismo , Hipoxia Encefálica/patología , Masculino , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/patología , Ratas , Ratas Sprague-Dawley
9.
Behav Brain Res ; 416: 113568, 2022 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-34499936

RESUMEN

Hypobaric Hypoxia (HH) is known to cause oxidative stress in the brain that leads to spatial memory deficit and neurodegeneration. For decades therapeutic hypothermia is used to treat global and focal ischemia in preserving brain functions that proved to be beneficial in humans and rodents. Considering these previous reports, the present study was designed to establish the therapeutic potential of hypothermia preconditioning on HH induced spatial memory, biochemical and morphological changes in adult rats. Male Sprague Dawley rats were exposed to HH (7620 m, ~ 282 mmHg) for 1, 3 and 7 days with and without hypothermic preconditioning. Spatial learning memory was assessed by Morris water maze (MWM) test along with evaluation of hippocampal pyramidal neuron damage by histological study. Oxidative stress was measured by studying the levels of nitric oxide (NO), reactive oxygen species (ROS), lipid peroxidation (LPO), oxidized and reduced glutathione (GSSG and GSH). Results of MWM test indicated prolonged path length and latency to reach the platform in HH groups that regained to normal in cold pre-treated groups. A likely neurodegeneration was evident in HH groups that lessen in the cold pre-treated groups. Hypothermic preconditioning prevented spatial memory impairment and neurodegeneration in animals subjected to HH via decreasing the NO, ROS and LPO compared to control animals. The GSH level and GSH/GSSG ratio was found to be higher in preconditioned animals as compared to respective HH exposed animals, indicative of redox scavenging and restoration of hippocampal neuronal structure as well as spatial memory. Therefore, hypothermic preconditioning improves spatial memory deficit by reducing HH induced oxidative stress and hippocampal neurodegeneration, hence can be used as a multi-target prophylactic measure to combat HH induced neurodegeneration.


Asunto(s)
Hipocampo/fisiopatología , Hipotermia/inducido químicamente , Hipoxia Encefálica/fisiopatología , Trastornos de la Memoria/fisiopatología , Células Piramidales/patología , Memoria Espacial/fisiología , Animales , Glutatión/metabolismo , Hipocampo/patología , Hipoxia Encefálica/patología , Peroxidación de Lípido/fisiología , Masculino , Prueba del Laberinto Acuático de Morris , Estrés Oxidativo/fisiología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno
10.
RSC Adv ; 12(20): 12310-12320, 2022 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-35480352

RESUMEN

Graphene quantum dots (GQDs) are a luminescent class of carbon nanomaterials with a graphene-like core structure, possessing quantum confinement and edge effects. They have gained importance in the biological world due to their inherent biocompatibility, good water dispersibility, excellent fluorescence and photostability. The improved properties of GQDs require the logical enactment of functional groups, which can be easily attained through post-synthetic non-covalent routes of modification. In this regard, the present work has for the first time employed a simple one-pot post-modification method utilizing the salt of amino caproic acid, an FDA approved reagent. The adsorption of the modifier on GQDs with varying weight ratios is characterized through DLS, zeta potential, Raman, absorption and fluorescence spectroscopy. A decrease of 20% in the fluorescence intensity with an increase in the modifier ratio from 1 to 1000 and an increased DLS size as well as zeta potential demonstrate the efficient modification as well as higher stability of the modified GQDs. The modified GQDs with a high weight ratio (1 : 100) of the modifier showed superior ability to sense dopamine, a neurotransmitter, as well as competent biofilm degradation ability. The modified GQDs could sense more efficiently than pristine GQDs, with a sensitivity as low as 0.06 µM (limit of detection) and 90% selectivity in the presence of other neurotransmitters. The linear relationship showed a decrease in the fluorescence intensity with increasing dopamine concentration from 0.0625 µM to 50 µM. Furthermore, the efficiency of the modified GQDs was also assessed in terms of their antibiofilm effect against Staphylococcus aureus. The unmodified GQDs showed only 10% disruption of the adhered bacterial colonies, while the modified GQDs (1 : 100) showed significantly more than 60% disruption of the biofilm, presenting the competency of the modified GQDs. The unique modifications of GQDs have thus proven to be an effective method for the proficient utilization of zero-dimensional carbon nanomaterials for biosensing, bioimaging, antibacterial and anti-biofilm applications.

11.
J Psychiatr Res ; 149: 155-161, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35276632

RESUMEN

The present study is conducted to understand the association of mood profile with the kynurenine pathway (KP) metabolites, and cerebral hemodynamics in freshly recruited central armed forces personnel. Profile of Mood States questionnaire was utilized to assess mood profile, and Total Mood Disturbance (TMD) score was calculated. Transcranial Doppler was used to record blood flow velocity bilaterally of the middle cerebral artery. Chromatographic profile of the kynurenine metabolites was obtained in serum. Further, personnel were stratified according to sociodemographic variables (gender, age and diet) to observe the changes in their KP metabolic status. An activation of the kynurenic acid branch of the KP and the reduction in the mean blood flow velocity, and an increase in Gosling pulsatility index (PI) were observed in females having high TMD score. On gender comparative analysis, kynurenine metabolites of quinolinic acid branch and serotonin were significantly high in males. In males, with increase in age, a significant increase in the quinolinic acid branch of the KP was observed. Furthermore, a significant difference in level metabolites of the KP among the vegetarian and non-vegetarian groups was also observed. In conclusion we observed that increased TMD score was associated with cerebral hypoperfusion and higher vascular resistance along with activation of the KP. Our findings highlighted the importance of multi-facet brain function to showcase the close interaction of various dimensionalities and true picture of the assessee.


Asunto(s)
Quinurenina , Personal Militar , Animales , Circulación Cerebrovascular , Femenino , Gansos/metabolismo , Humanos , Masculino , Ácido Quinolínico/metabolismo
12.
Food Chem ; 127(3): 1309-16, 2011 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-25214131

RESUMEN

A novel environmentally friendly technique, subcritical water extraction (SWE) was employed for the extraction of antioxidant compounds from Seabuckthorn leaves (SBT). Antioxidant activity of the extracts was evaluated using commonly accepted chemical assays. Also, present study reports the cytoprotective and antioxidant properties of SBT against tertiary-butyl hydroperoxide (tert-BOOH) induced oxidative stress in murine macrophages (Raw 264.7). Exposure of cells to tert-BOOH resulted, increase in cytotoxicity, reactive oxygen species (ROS) production and decrease in mitochondrial membrane potential, which is responsible for fall in intracellular antioxidant levels. Pretreatment of cells with SBT extracts inhibited cytotoxicity, ROS production and maintained antioxidants levels similar to that of control cells. The chemical composition of the SWE extracts studied showed total phenol content (76.07-93.72mg/g GAE) and total flavonoid content (47.06-66.03mg/g rutin). Further, some of its phenolic constituents; (1) Quercetin-3-galactoside, (2) Kaempferol and (3) Isorhamnetin were quantified by RP-HPLC.

13.
Int J Neurosci ; 121(5): 279-88, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21348795

RESUMEN

High altitude (HA) generates a deleterious effect known as hypobaric hypoxia (HBH). This causes severe physiological and psychological changes such as acute mountain sickness (AMS) and cognitive functions in terms of learning and memory. The present study has evaluated the effect of cholinesterase inhibitors on memory consolidation following HBH. Adult male Sprague Dawley rats (80-90 days old) with an average body weight of 250 ± 25 g were used. Rats were assessed memory consolidation by using Morris water maze (MWM) for 8 days. After assessment of memory consolidation, rats were then exposed to HBH in stimulated chamber for 7 days at 6,100 m. After exposure to HBH, the memory consolidation of rats has been assessed in MWM. The results showed that there was memory consolidation impairment in HBH-exposed rats as compared to normoxic rats in terms of time spent in quaradents, rings, and counters. The rats which have been treated with physostigmine (PHY) and galantamine (GAL) showed better time spent in quaradents, rings, and counters as compared with hypoxic rats. In conclusion, the cholinesterase inhibitors could ameliorate the impairment of memory consolidation following HBH.


Asunto(s)
Mal de Altura/tratamiento farmacológico , Inhibidores de la Colinesterasa/farmacología , Hipoxia Encefálica/tratamiento farmacológico , Trastornos de la Memoria/tratamiento farmacológico , Memoria/efectos de los fármacos , Acetilcolina/agonistas , Acetilcolina/fisiología , Presión del Aire , Mal de Altura/complicaciones , Mal de Altura/enzimología , Animales , Modelos Animales de Enfermedad , Galantamina/farmacología , Hipoxia Encefálica/complicaciones , Hipoxia Encefálica/enzimología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Memoria/fisiología , Trastornos de la Memoria/enzimología , Trastornos de la Memoria/etiología , Fisostigmina/farmacología , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Resultado del Tratamiento
14.
Int J Radiat Biol ; 97(11): 1606-1616, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34402374

RESUMEN

PURPOSE: The model biological organism Drosophila melanogaster has been utilized to assess the effect of extremely low-frequency electromagnetic field (ELF-EMF) on locomotion, longevity, developmental dynamics, cell viability and oxidative stress. MATERIALS AND METHOD: Developmental stages of Drosophila melanogaster (Oregon R strain) individually exposed to ELF-EMF (75 Hz, 550 µT) for 6 h once for acute exposure. For chronic exposure, complete life cycle of fly, that is, egg to adult fly was exposed to ELF-EMF for 6 h daily. The effect of exposure on their crawling and climbing ability, longevity, development dynamics, cellular damage and oxidative stress (generation of reactive oxygen species (ROS)) was evaluated. RESULTS: The crawling ability of larvae was significantly (p < .05) reduced on acute (third stage instar larvae) as well as chronic exposure (F0 and F1 larvae). When locomotion of flies was tested using climbing assay, no alteration was observed in their climbing ability under both acute and chronic exposure; however, when their speed of climbing was compared, a significant decrease in speed of F1 flies was observed (p = .0027) on chronic exposure. The survivability of flies was significantly affected under chronic and acute exposure (at third stage instar larvae). In case of acute exposure of the third stage instar larvae, although all the flies were eclosed by the 17th day, there was a significant decline in the number of flies (p = .007) in comparison to control. While in case of chronic exposure apart from low number of flies eclosed in comparison to control, there was delay in eclosion by one day (p = .0004). Using trypan blue assay, the internal gut damage of third stage instar larvae was observed. Under acute exposure condition at third stage instar larvae, 30% larvae has taken up trypan blue, while only 10% larvae from acute exposure at adult stage. On chronic exposure, 50% larvae of the F1 generation have taken up trypan blue. On evaluation of oxidative stress, there is a significant rise in ROS in case of acute exposure at third stage instar larvae (p = .0004), adult fly stage (p = .0004) and chronic exposure (p = .0001). CONCLUSION: ELF-EMF has maximum effects on acute exposure of third stage instar larvae and chronic exposure (egg to adult fly stage). These results suggest that electromagnetic radiations, though, have become indispensible part of our lives but they plausibly affect our health.


Asunto(s)
Drosophila melanogaster , Campos Electromagnéticos , Animales , Campos Electromagnéticos/efectos adversos , Larva , Estrés Oxidativo , Especies Reactivas de Oxígeno , Azul de Tripano
15.
Front Pharmacol ; 12: 669701, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34326768

RESUMEN

Hypobaric hypoxia (HH) is a stressful condition, which is more common at high altitudes and can impair cognitive functions. Ginkgo biloba L. leaf extract (GBE) is widely used as herbal medicine against different disorders. Its ability to improve cognitive functions, reduce oxidative stress, and promote cell survival makes it a putative therapeutic candidate against HH. The present study has been designed to explore the effect of GBE on HH-induced neurodegeneration and memory impairment as well as possible signaling mechanisms involved. 220-250 gm (approximately 6- to 8-week-old) Sprague Dawley rats were randomly divided into different groups. GBE was orally administered to respective groups at a dose of 100 mg/kg/day throughout the HH exposure, i.e., 14 days. Memory testing was performed followed by hippocampus isolation for further processing of different molecular and morphological parameters related to cognition. The results indicated that GBE ameliorates HH-induced memory impairment and oxidative damage and reduces apoptosis. Moreover, GBE modulates the activity of the small conductance calcium-activated potassium channels, which further reduces glutamate excitotoxicity and apoptosis. The exploration of the downstream signaling pathway demonstrated that GBE administration prevents HH-induced small conductance calcium-activated potassium channel activation, and that initiates pro-survival machinery by activating extracellular signal-regulated kinase (ERK)/calmodulin-dependent protein kinase II (CaMKII) and the cAMP response element-binding protein (CREB) signaling pathway. In summary, the current study demonstrates the beneficial effect of GBE on conditions like HH and provides various therapeutic targets involved in the mechanism of action of GBE-mediated neuroprotection.

16.
Exp Brain Res ; 203(3): 583-92, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20458473

RESUMEN

Cognitive functions especially learning and memory are severely affected by high altitude (HA) exposure. Hypobaric hypoxia (HBH) encountered at HA is known to cause oxidative stress, alterations of neurotransmitters and cognitive impairment. We hypothesized that alteration in cholinergic system may be involved in HBH-induced learning impairment. The present study has investigated the cholinergic dysfunctions associated with simulated HBH-induced impairment of learning in rats and protective role of acetylcholine esterase inhibitors (AChEIs). Male Sprague-Dawley rats were exposed to HBH equivalent to 6,100 m for 7 days in a simulated decompression chamber. After stipulated period of exposure, learning ability was assessed using Morris water maze (MWM) task. Cholinergic markers like acetylcholine (ACh) and acetyl cholinesterase (AChE) were evaluated from cortex and hippocampus. Morphological changes were evaluated from cortex, CA1, and CA3 region of hippocampus by Nissle staining and by electron microscopy. We found that exposure to HBH led to impairment of learning ability in MWM task, and it was accompanied by decrease in ACh level, increase in AChE activity, and revealed critical cellular damage. Administration of AChEIs like physostigmine (PHY) and galantamine (GAL) resulted in amelioration of the deleterious effects induced by HBH. The AChEIs were also able to restore the neuronal morphology. Our data suggest that cholinergic system is affected by HBH, and AChEIs were able to improve HBH-induced learning impairment in rats.


Asunto(s)
Inhibidores de la Colinesterasa/farmacología , Hipoxia/complicaciones , Discapacidades para el Aprendizaje/complicaciones , Discapacidades para el Aprendizaje/tratamiento farmacológico , Nootrópicos/farmacología , Percepción Espacial/efectos de los fármacos , Acetilcolina/metabolismo , Acetilcolinesterasa/metabolismo , Animales , Región CA1 Hipocampal/efectos de los fármacos , Región CA1 Hipocampal/metabolismo , Región CA1 Hipocampal/patología , Región CA3 Hipocampal/efectos de los fármacos , Región CA3 Hipocampal/metabolismo , Región CA3 Hipocampal/patología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Galantamina/farmacología , Discapacidades para el Aprendizaje/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Fisostigmina/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Percepción Espacial/fisiología
17.
ACS Chem Neurosci ; 11(20): 3194-3203, 2020 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-33006881

RESUMEN

The world is experiencing one of the major viral outbreaks of this millennium, caused by a plus sense single-stranded RNA virus belonging to the Coronaviridae family, COVID-19, declared as pandemic by WHO. The clinical manifestations vary from asymptomatic to mild symptoms like fever, dry cough, and diarrhea, with further increase in severity leading to the development of acute respiratory distress syndrome. Though primary manifestations are respiratory and cardiac, various studies have shown the neuroinvasive capability of this virus resulting in neurological complications, which sometimes can precede common typical symptoms like fever and cough. Common neurological symptoms are headache, dizziness, anosmia, dysgeusia, confusion, and muscle weakening, progressing toward severe complications like cerebrovascular disease, seizures, or paralysis. Older adults and critically ill people are in the high risk group and have shown severe neurological symptoms upon infection. COVID-19 also has a profound impact on the mental health of people across the world. In this review, we briefly discuss the neurological pathologies and psychological impact due to COVID-19, which has not only stressed the physical health of people but has also created social and economic problems resulting in mental health issues.


Asunto(s)
Infecciones por Coronavirus/patología , Infecciones por Coronavirus/psicología , Trastornos Mentales/virología , Enfermedades del Sistema Nervioso/virología , Neumonía Viral/patología , Neumonía Viral/psicología , Betacoronavirus , COVID-19 , Humanos , Pandemias , SARS-CoV-2
18.
Biochim Biophys Acta Mol Basis Dis ; 1866(7): 165769, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32184133

RESUMEN

Brain is well known for its disproportionate oxygen consumption and high energy-budget for optimal functioning. The decrease in oxygen supply to brain, thus, necessitates rapid activation of adaptive pathways - the absence of which manifest into vivid pathological conditions. Amongst these, oxygen sensing in glio-vascular milieu and H2S-dependent compensatory increase in cerebral blood flow (CBF) is a major adaptive response. We had recently demonstrated that the levels of H2S were significantly decreased during chronic hypobaric hypoxia (HH)-induced neuro-pathological effects. The mechanistic basis of this phenomenon, however, remained to be deciphered. We, here, describe experimental evidence for marked limitation of cysteine during HH - both in animal model as well as human volunteers ascending to high altitude. We show that the preservation of brain cysteine level, employing cysteine pro-drug (N-acetyl-L-cysteine, NAC), markedly curtailed effects of HH - not only on endogenous H2S levels but also, impairment of spatial reference memory in our animal model. We, further, present multiple lines of experimental evidence that the limitation of cysteine was causally governed by physiological propensity of brain to utilize cysteine, in cystathionine beta synthase (CBS)-dependent manner, past its endogenous replenishment potential. Notably, decrease in the levels of brain cysteine manifested despite positive effect (up-regulation) of HH on endogenous cysteine maintenance pathways and thus, qualifying cysteine as a conditionally essential nutrient (CEN) during HH. In brief, our data supports an adaptive, physiological role of CBS-mediated cysteine-utilization pathway - activated to increase endogenous levels of H2S - for optimal responses of brain to hypobaric hypoxia.


Asunto(s)
Mal de Altura/metabolismo , Encéfalo/metabolismo , Cistationina betasintasa/genética , Cisteína/metabolismo , Sulfuro de Hidrógeno/metabolismo , Acetilcisteína/farmacología , Adaptación Fisiológica , Adulto , Mal de Altura/tratamiento farmacológico , Mal de Altura/genética , Mal de Altura/patología , Animales , Encéfalo/patología , Circulación Cerebrovascular/efectos de los fármacos , Circulación Cerebrovascular/genética , Cistationina betasintasa/metabolismo , Modelos Animales de Enfermedad , Metabolismo Energético/genética , Humanos , Hipoxia/tratamiento farmacológico , Hipoxia/genética , Hipoxia/metabolismo , Masculino , Consumo de Oxígeno/genética , Profármacos/farmacología , Ratas , Adulto Joven
19.
Neurobiol Dis ; 34(2): 230-44, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19385055

RESUMEN

Hypobaric hypoxia leads to cognitive dysfunctions due to increase in intracellular calcium through ion channels. The purpose of this study was to examine the temporal contribution of L-type calcium channels and N-methyl-D-aspartate receptors (NMDARs) in mediating neuronal death in male Sprague Dawley rats exposed to hypobaric hypoxia simulating an altitude of 25,000 ft for different durations. Decreasing exogenous calcium loads by blocking voltage-gated calcium influx with isradipine (2.5 mg kg(-1)), and its efficacy in providing neuroprotection and preventing memory impairment following hypoxic exposure was also investigated. Effect of isradipine on calcium-dependent enzymes mediating oxidative stress and apoptotic cell death was also studied. Blocking of L-type calcium channels with isradipine reduced hypoxia-induced activation of calcium dependent xanthine oxidases, monoamine oxidases, cytosolic phospholipase A(2) and cycloxygenases (COX-2) along with concomitant decrease in free radical generation and cytochrome c release. Increased expression of calpain and caspase 3 was also observed following exposure to hypobaric hypoxia along with augmented neurodegeneration and memory impairment which was adequately prevented by isradipine administration. Administration of isradipine during hypoxic exposure protected the hippocampal neurons following 3 and 7 days of exposure to hypobaric hypoxia along with improvement in spatial memory.


Asunto(s)
Canales de Calcio Tipo L/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipoxia Encefálica/tratamiento farmacológico , Isradipino/farmacología , Trastornos de la Memoria/tratamiento farmacológico , Receptores de N-Metil-D-Aspartato/efectos de los fármacos , Mal de Altura/tratamiento farmacológico , Mal de Altura/metabolismo , Mal de Altura/fisiopatología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Proteínas Reguladoras de la Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Cámaras de Exposición Atmosférica/efectos adversos , Presión Atmosférica , Bloqueadores de los Canales de Calcio/farmacología , Bloqueadores de los Canales de Calcio/uso terapéutico , Canales de Calcio Tipo L/metabolismo , Señalización del Calcio/efectos de los fármacos , Señalización del Calcio/fisiología , Radicales Libres/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiopatología , Hipoxia Encefálica/metabolismo , Hipoxia Encefálica/fisiopatología , Isradipino/uso terapéutico , Masculino , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/fisiopatología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo
20.
Neurobiol Dis ; 34(1): 23-39, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19154788

RESUMEN

Hypobaric hypoxia induced memory impairment has been attributed to several factors including increased oxidative stress, depleted mitochondrial bioenergetics, altered neurotransmission and apoptosis. This multifactorial response of the brain to hypobaric hypoxia limits the use of therapeutic agents that target individual pathways for ameliorating hypobaric hypoxia induced memory impairment. The present study aimed at exploring the therapeutic potential of a bacoside rich leaf extract of Bacopa monniera in improving the memory functions in hypobaric conditions. The learning ability was evaluated in male Sprague Dawley rats along with memory retrieval following exposure to hypobaric conditions simulating an altitude of 25,000 ft for different durations. The effect of bacoside administration on apoptosis, cytochrome c oxidase activity, ATP levels, and oxidative stress markers and on plasma corticosterone levels was investigated. Expression of NR1 subunit of N-methyl-d-aspartate receptors, neuronal cell adhesion molecules and was also studied along with CREB phosphorylation to elucidate the molecular mechanisms of bacoside action. Bacoside administration was seen to enhance learning ability in rats along with augmentation in memory retrieval and prevention of dendritic atrophy following hypoxic exposure. In addition, it decreased oxidative stress, plasma corticosterone levels and neuronal degeneration. Bacoside administration also increased cytochrome c oxidase activity along with a concomitant increase in ATP levels. Hence, administration of bacosides could be a useful therapeutic strategy in ameliorating hypobaric hypoxia induced cognitive dysfunctions and other related neurological disorders.


Asunto(s)
Bacopa , Hipoxia/fisiopatología , Trastornos de la Memoria/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Adenosina Trifosfato/metabolismo , Animales , Apoptosis/efectos de los fármacos , Moléculas de Adhesión Celular Neuronal/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Masculino , Fosforilación/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Percepción Espacial/efectos de los fármacos
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