Study of neurotoxic effects and underlying mechanisms of aconitine on cerebral cortex neuron cells

(1) Background: Depression is one of the overwhelming public health problems. Alleviating hippocampus injury may prevent depression development. Herein, we established the chronic unpredictable mild stress (CUMS) model and aimed to investigate whether aerobic exercise (AE) could alleviate CUMS induced depression-like behaviors and hippocampus injury. (2) Methods: Forty-eight healthy male Sprague-Dawley rats (200 ± 20 g) were randomly divided into 4 groups (control, CUMS, CUMS + 7 days AE, CUMS + 14 days AE). Rats with AE treatments were subjected to 45 min treadmill per day. (3) Results: AE intervention significantly improved CUMS-induced depressive behaviors, e.g., running square numbers and immobility time assessed by the open field and forced swimming test, suppressed hippocampal neuron apoptosis, reduced levels of phosphorylation of NMDA receptor and homocysteine in hippocampus, as well as serum glucocorticoids, compared to the CUMS rats. In contrast, AE upregulated phosphorylation of AMPAR receptor and brain-derived neurotrophic factor (BDNF) hippocampus in CUMS depression rats. The 14 day-AE treatment exhibited better performance than 7 day-AE on the improvement of the hippocampal function. (4) Conclusion: AE might be an efficient strategy for prevention of CUMS-induced depression via ameliorating hippocampus functions. Underlying mechanisms may be related with glutamatergic system, the neurotoxic effects of homocysteine, and/or influences in glucocorticoids-BDNF expression interaction.

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Neurotoxic Effects of Tetrahydroisoquinolines and Underlying Mechanisms

Experimental Neurobiology ◽

10.5607/en.2010.19.2.63 ◽

2010 ◽

Vol 19 (2) ◽

pp. 63-70 ◽

Cited By ~ 7

Author(s):

Young-Joon Surh ◽

Hyun-Jung Kim

Keyword(s):

Neurotoxic Effects ◽

Underlying Mechanisms

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Selective regional alterations in the content or distribution of neuronal and glial cytoskeletal proteins in brain of rats chronically exposed to 2,5-hexanedione

Toxicology and Industrial Health ◽

10.1191/0748233702th154oa ◽

2002 ◽

Vol 18 (7) ◽

pp. 333-341 ◽

Cited By ~ 2

Author(s):

Mari Luz Hernandez-Viadel ◽

Regina Rodrigo ◽

Vicente Felipo

Keyword(s):

Cerebral Cortex ◽

Motor Function ◽

Molecular Layer ◽

Cytoskeletal Proteins ◽

Brain Areas ◽

Protein Map ◽

Neurotoxic Effects ◽

Transfer Of Information ◽

System Hexane ◽

Regional Selectivity

Hexane is used in many industrial processes and induces neurotoxic effects in the central and peripheral nervous system. Hexane is metabolized to 2,5-hexanedione, which is the neurotoxic agent. Continued exposure to hexane or 2,5-hexanedione results in loss of sensorial and motor function in arms and legs and to alterations in axonal neurofilament proteins. The effects of 2,5-hexanedione on different cytoskeletal proteins in different brain areas have not been studied in detail. The aim of this work was to study the effects of chronic exposure of rats to 2,5-hexanedione (1% in the drinking water) on tubulin, neurofilament NF-L, microtubule-associated protein MAP-2, and on glial fibrillary acidic protein (GFAP), in cerebellum, hippocampus and cerebral cortex. The amount of each protein was determined by immunoblotting and its distribution was analysed by immunohistochemistry. The results obtained show a regional selectivity in the 2,5-hexanedione effects on cytoskeletal proteins. NF-L content decreased in all brain areas. MAP-2 decreased in cerebellum and hippocampus and tubulin decreased only in cerebellum. GFAP decreased only in cerebral cortex, but its distribution was altered in cerebellum, with increased content in the granular layer and decreased content in the molecular layer. The area most affected was the cerebellum, where all the proteins analysed were altered. These cytoskeletal proteins alterations may impair the transfer of information involved in the regulation by the cerebellum of motor function and contribute to the altered motor performance in rats exposed to 2,5-hexanedione and humans exposed to hexane.

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Effect of atorvastatin on AGEs-induced injury of cerebral cortex via inhibiting NADPH oxidase -NF-κB pathway in ApoE-/- mice

10.21203/rs.3.rs-15490/v1 ◽

2020 ◽

Author(s):

zhenhan li ◽

Peiye Yang ◽

Bo Feng

Keyword(s):

Cerebral Cortex ◽

Cognitive Impairment ◽

Nadph Oxidase ◽

Close Association ◽

Critical Role ◽

Control Group ◽

Oxidation Stress ◽

Potential Benefits ◽

Congo Red Staining ◽

Underlying Mechanisms

Abstract Background There is close association between type 2 diabetes and cognitive impairment. AGEs-RAGE pathway plays critical role to induce neurodegenerative encephalopathy. Statins can reduce the expression of AGEs-induced RAGE in aorta. It is not clear whether statins have potential benefits on AGEs-induced cognitive impairment. In this study, the effects of atorvastatin on inflammation and oxidation stress in cerebral cortex were investigated and the underlying mechanisms were explored. Methods 40 male ApoE-/- mice were randomly divided into four groups: control, AGEs (30mg/kg/day), AGEs (30mg/kg/day) + ALT711 (1mg/kg/day) and AGEs (30mg/kg/day) + ATV (10mg/kg/day). Aβ formation in cerebral cortex was assessed through Congo red staining and the functional state of neurons were evaluated by Nissl's staining. Immunostaining was performed to assess the accumulation of AGEs in the cerebral cortex. The expressions of mRNA and protein of RAGE, NF-κB p65 and NADPH oxidase p47phox were detected by Real-time PCR and Western blot. Results There were significant increases in AGE deposit, Aβ formation and the expressions of RAGE, NF-κB p65 and NADPH oxidase p47phox and decrease in Nissl body in AGEs group compared with control group. ALT711 recovered above change compared with AGEs group. Atorvastatin reduced Aβ formation and suppressed AGEs-induced expressions of NF-κB p65 and NADPH oxidase p47phox. Atorvastatin has little effects on AGE deposit and RAGE expressions. Conclusions Atorvastatin alleviates AGEs-induced neuronal impairment via inhibiting NADPH oxidase-NF-κB pathway and is of benefit in preventing the progression of degenerative encephalopathy.

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Quantification of Cortical Surface Convolution in the Developing Ferret and Human Infant

ASME 2009 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2009-205716 ◽

2009 ◽

Author(s):

Andrew K. Knutsen ◽

Jason E. Hill ◽

Jeffrey J. Neil ◽

Terrie E. Inder ◽

Philip V. Bayly

Keyword(s):

Cerebral Cortex ◽

Human Infant ◽

Cortical Surface ◽

Human Cerebral Cortex ◽

Direct Measurements ◽

Underlying Mechanisms ◽

Insight Into ◽

Sulcal Depth

The human cerebral cortex undergoes folding from the 5th fetal month into the first post-natal year. Disturbances of folding have serious and lasting consequences, but the mechanism is not well understood. Van Essen [1] has hypothesized that axonal tension between strongly interconnected regions draws them together and induces outward folds. However, no direct measurements have confirmed this theory. As measures of shape, cortical curvature and sulcal depth changes during development can help provide insight into underlying mechanisms of growth.

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Propofol Compared with Isoflurane Inhibits Mitochondrial Metabolism in Immature Swine Cerebral Cortex

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2013.229 ◽

2014 ◽

Vol 34 (3) ◽

pp. 514-521 ◽

Cited By ~ 28

Author(s):

Masaki Kajimoto ◽

Douglas B Atkinson ◽

Dolena R Ledee ◽

Ernst-Bernhard Kayser ◽

Phil G Morgan ◽

...

Keyword(s):

Cerebral Cortex ◽

Near Infrared ◽

Metabolic Phenotype ◽

Glycolytic Flux ◽

Propofol Infusion Syndrome ◽

Immature Brain ◽

The Common ◽

Underlying Mechanisms ◽

Glycogen Stores ◽

Hypoxic State

Anesthetics used in infants and children are implicated in the development of neurocognitive disorders. Although propofol induces neuroapoptosis in developing brain, the underlying mechanisms require elucidation and may have an energetic basis. We studied substrate utilization in immature swine anesthetized with either propofol or isoflurane for 4 hours. Piglets were infused with 13-Carbon-labeled glucose and leucine in the common carotid artery to assess citric acid cycle (CAC) metabolism in the parietal cortex. The anesthetics produced similar systemic hemodynamics and cerebral oxygen saturation by near-infrared spectroscopy. Compared with isoflurane, propofol depleted ATP and glycogen stores. Propofol decreased pools of the CAC intermediates, citrate, and α-ketoglutarate, while markedly increasing succinate along with decreasing mitochondrial complex II activity. Propofol also inhibited acetyl-CoA entry into the CAC through pyruvate dehydrogenase, while promoting glycolytic flux with marked lactate accumulation. Although oxygen supply appeared similar between the anesthetic groups, propofol yielded a metabolic phenotype that resembled a hypoxic state. Propofol impairs substrate flux through the CAC in the immature cerebral cortex. These impairments occurred without systemic metabolic perturbations that typically accompany propofol infusion syndrome. These metabolic abnormalities may have a role in the neurotoxity observed with propofol in the vulnerable immature brain.

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Use of artificial ion channels for quasi-intracellular recording of cerebral cortex neuron activity

Neuroscience and Behavioral Physiology ◽

10.1007/bf02461932 ◽

1997 ◽

Vol 27 (6) ◽

pp. 702-707 ◽

Cited By ~ 4

Author(s):

M. Yu. Inyushin ◽

V. Yu. Tsytsarev ◽

A. Yu. Ignashchenkova ◽

D. N. Lenkov

Keyword(s):

Cerebral Cortex ◽

Ion Channels ◽

Intracellular Recording ◽

Neuron Activity ◽

Cortex Neuron

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Histone Methyltransferases SUV39H1 and G9a and DNA Methyltransferase DNMT1 in Penumbra Neurons and Astrocytes after Photothrombotic Stroke

International Journal of Molecular Sciences ◽

10.3390/ijms222212483 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12483

Author(s):

Svetlana Sharifulina ◽

Valentina Dzreyan ◽

Valeria Guzenko ◽

Svetlana Demyanenko

Keyword(s):

Dna Methylation ◽

Cerebral Cortex ◽

Dna Methyltransferase ◽

Intracellular Localization ◽

Protein Targets ◽

Histone Methyltransferases ◽

Neurotoxic Effects ◽

Microscopy Analysis ◽

Photothrombotic Stroke ◽

Epigenetic Processes

Background: Cerebral ischemia, a common cerebrovascular disease, is one of the great threats to human health and new targets for stroke therapy are needed. The transcriptional activity in the cell is regulated by epigenetic processes such as DNA methylation/demethylation, acetylation/deacetylation, histone methylation, etc. Changes in DNA methylation after ischemia can have both neuroprotective and neurotoxic effects depending on the degree of ischemia damage, the time elapsed after injury, and the site of methylation. Methods: In this study, we investigated the changes in the expression and intracellular localization of DNA methyltransferase DNMT1, histone methyltransferases SUV39H1, and G9a in penumbra neurons and astrocytes at 4 and 24 h after stroke in the rat cerebral cortex using photothrombotic stroke (PTS) model. Methods of immunofluorescence microscopy analysis, apoptosis analysis, and immunoblotting were used. Additionally, we have studied the effect of DNMT1 and G9a inhibitors on the volume of PTS-induced infarction and apoptosis of penumbra cells in the cortex of mice after PTS. Results: This study has shown that the level of DNMT1 increased in the nuclear and cytoplasmic fractions of the penumbra tissue at 24 h after PTS. Inhibition of DNMT1 by 5-aza-2′-deoxycytidine protected cells of PTS-induced penumbra from apoptosis. An increase in the level of SUV39H1 in the penumbra was found at 24 h after PTS and G9a was overexpressed at 4 and 24 h after PTS. G9a inhibitors A-366 and BIX01294 protected penumbra cells from apoptosis and reduced the volume of PTS-induced cerebral infarction. Conclusion: Thus, the data obtained show that DNA methyltransferase DNMT1 and histone methyltransferase G9a can be potential protein targets in ischemic penumbra cells, and their inhibitors are potential neuroprotective agents capable of protecting penumbra cells from postischemic damage to the cerebral cortex.

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Socioeconomic Disparities and Sexual Dimorphism in Neurotoxic Effects of Ambient Fine Particles on Youth IQ: A Longitudinal Analysis

10.1101/207589 ◽

2017 ◽

Author(s):

Pan Wang ◽

Catherine Tuvblad ◽

Diana Younan ◽

Meredith Franklin ◽

Fred Lurmann ◽

...

Keyword(s):

Sexual Dimorphism ◽

Cognitive Abilities ◽

Fine Particles ◽

Family Socioeconomic Status ◽

Early Life Exposure ◽

The Social ◽

Neurotoxic Effects ◽

Underlying Mechanisms ◽

One Year ◽

Shed Light

AbstractMounting evidence indicates that early-life exposure to particulate air pollutants pose threats to children’s cognitive development, but studies about the neurotoxic effects associated with exposures during adolescence remain unclear. We examined whether exposure to ambient fine particles (PM2.5) at residential locations affects intelligence quotient (IQ) during pre-/early-adolescence (ages 9-11) and emerging adulthood (ages 18-20) in a demographically-diverse population (N = 1,360) residing in Southern California. Increased ambient PM2.5levels were associated with decreased IQ scores. This association was more evident for Performance IQ (PIQ), but less for Verbal IQ, assessed by the Wechsler Abbreviated Scale of Intelligence. For each inter-quartile (7.73 μg/m3) increase in one-year PM2.5preceding each assessment, the average PIQ score decreased by 3.08 points (95% confidence interval = [−6.04, −0.12]) accounting for within-family/within-individual correlations, demographic characteristics, family socioeconomic status (SES), parents’ cognitive abilities, neighborhood characteristics, and other spatial confounders. The adverse effect was 150% greater in low SES families and 89% stronger in males, compared to their counterparts. Better understanding of the social disparities and sexual dimorphism in the adverse PM2.5-IQ effects may help elucidate the underlying mechanisms and shed light on prevention strategies.

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