Clinical concentration of sevoflurane had no short-term effect on the myelin sheath in prefrontal cortex of aged marmosets
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ABSTRACT:
SUBMITTER: Miao Z
PROVIDER: S-EPMC11338887 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Background Surgery under general anesthesia leads to neural injury, especially in older patients. Sevoflurane anesthesia without surgery for 2 h does not induce neural injury, however, whether prolonger sevoflurane anesthesia without surgery has the same consequence is still unknown. Methods In the present study, aged marmosets were exposed to a clinical concentration of sevoflurane (1.5–2%) for 6 h to access the effects of prolonged sevoflurane anesthesia on the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), Caspase3 activity and myelin formation in the brain. Results Sevoflurane anesthesia did not alter the expression of IL-6 (120.1 ± 2.21 vs. 120.8 ± 2.25, p = 0.74), TNF-α (189.3 ± 31.35 vs. 218.7 ± 21.47, p = 0.25) and Caspase3 (57.35 ± 1.54 vs. 58.67 ± 1.19, p = 0.53) in the prefrontal cortex (PFC) of aged marmosets. The amount of MBP expression (60.99 ± 6.21 vs. 58.91 ± 2.71, p = 0.77) did not change following sevoflurane exposure. Conclusion Sevoflurane anesthesia did not increase the levels of IL-6 and TNF-α, activated the the expression of Caspase3, and induced myelination deficits in the PFC of aged marmosets.
| S-EPMC9281875 | biostudies-literature
Project description:Studies aimed at investigating brain regions involved in arousal state control have been traditionally limited to subcortical structures. In the current study, we tested the hypothesis that inactivation of prefrontal cortex, but not two subregions within parietal cortex-somatosensory barrel field and medial/lateral parietal association cortex-would suppress arousal, as measured by an increase in anesthetic sensitivity. Male and female Sprague Dawley rats were surgically prepared for recording electroencephalogram and bilateral infusion into prefrontal cortex (N = 13), somatosensory barrel field (N = 10), or medial/lateral parietal association cortex (N = 9). After at least 10 days of post-surgical recovery, 156 μM tetrodotoxin or saline was microinjected into one of the cortical sites. Ninety minutes after injection, rats were anesthetized with 2.5% sevoflurane and the time to loss of righting reflex, a surrogate for loss of consciousness, was measured. Sevoflurane was stopped after 45 min and the time to return of righting reflex, a surrogate for return of consciousness, was measured. Tetrodotoxin-mediated inactivation of all three cortical sites decreased (p < 0.05) the time to loss of righting reflex. By contrast, only inactivation of prefrontal cortex, but not somatosensory barrel field or medial/lateral parietal association cortex, increased (p < 0.001) the time to return of righting reflex. Burst suppression ratio was not altered following inactivation of any of the cortical sites, suggesting that there was no global effect due to pharmacologic lesion. These findings demonstrate that prefrontal cortex plays a causal role in emergence from anesthesia and behavioral arousal.
| S-EPMC8299111 | biostudies-literature
Project description:Although short-term plasticity is believed to play a fundamental role in cortical computation, empirical evidence bearing on its role during behavior is scarce. Here we looked for the signature of short-term plasticity in the fine-timescale spiking relationships of a simultaneously recorded population of physiologically identified pyramidal cells and interneurons, in the medial prefrontal cortex of the rat, in a working memory task. On broader timescales, sequentially organized and transiently active neurons reliably differentiated between different trajectories of the rat in the maze. On finer timescales, putative monosynaptic interactions reflected short-term plasticity in their dynamic and predictable modulation across various aspects of the task, beyond a statistical accounting for the effect of the neurons' co-varying firing rates. Seeking potential mechanisms for such effects, we found evidence for both firing pattern-dependent facilitation and depression, as well as for a supralinear effect of presynaptic coincidence on the firing of postsynaptic targets.
| S-EPMC2562676 | biostudies-literature
Project description:Background: Inhalation anesthetics may trigger the hypothalamic–pituitary–adrenal (HPA) axis. FK-506 binding protein (FKBP5) is a critical factor that regulates the HPA axis and is associated with perioperative neurocognitive impairment. However, it is unclear how inhalation anesthetics affects the expression of FKBP5 in different neural cells in the brain. Methods: We used single-nucleus RNA sequencing to characterize hippocampal transcriptome profiles in the brains of aged marmosets and mice after sevoflurane anesthesia. Results: Higher levels of FKBP5 were found in the hippocampi of aged mice after sevoflurane anesthesia. Single nuclear RNA sequencing results from aged mice and marmosets showed that the increased expression of FKBP5 mainly occurred in microglia. The expression of FKBP5 in the hippocampi of aged marmosets and mice increased following long-term exposure to sevoflurane anesthesia. Additionally, the brains of these animals displayed a marked increase in the expression of FKBP5 in microglia after sevoflurane anesthesia. Conclusion: Long-term exposure to sevoflurane augments FKBP5 expression in the hippocampi of aged marmosets and mice, specifically in the microglia.
2024-10-30 | GSE234493 | GEO
Project description:Visual recognition is largely realized through neurons in the ventral stream, though recently, studies have suggested that ventrolateral prefrontal cortex (vlPFC) is also important for visual processing. While it is hypothesized that sensory and cognitive processes are integrated in vlPFC neurons, it is not clear how this mechanism benefits vision, or even if vlPFC neurons have properties essential for computations in visual cortex implemented via recurrence. Here, we investigated if vlPFC neurons in two male monkeys had functions comparable to visual cortex, including receptive fields, image selectivity, and the capacity to synthesize highly activating stimuli using generative networks. We found a subset of vlPFC sites show all properties, suggesting subpopulations of vlPFC neurons encode statistics about the world. Further, these vlPFC sites may be anatomically clustered, consistent with fMRI-identified functional organization. Our findings suggest that stable visual encoding in vlPFC may be a necessary condition for local and brain-wide computations.
| S-EPMC11324908 | biostudies-literature
Project description:ObjectiveIn the lipid-rich brain, lipids performed signaling processes associated with the control system of the cell cycle, stress, and inflammatory reactions, as well as maintained brain and cellular homeostasis. The effects of general anesthesia on brain impairment in the elderly were controversial and complex. The study sought to evaluate the effect of lipid metabolism in the brain of aged marmosets and mice under long-term exposure to sevoflurane.MethodsA total of 6 marmosets over 8-year-old and 10 mice aged 18 months were divided into the sevoflurane anesthesia and control groups, respectively. Marmosets in the sevoflurane anesthesia group were exposed to 1.5-2.5% sevoflurane and 100% O2 for 6 h. Mice anesthetized with sevoflurane were exposed to 3% sevoflurane and 60% O2 for 6 h. All prefrontal cortex tissues of marmosets and mice were harvested for the analysis of lipidomics.ResultsCompared to the control group, we found that phosphatidylethanolamine (PE) (18:0/22:5), PE (16:0/22:5), PE (18:2/22:5), PE (14:0/22:5), and PE (18:1/22:5) increased in the prefrontal cortex of marmosets in the sevoflurane group, while triglyceride (TAG)56:5-fatty acid (FA) 20:4, TAG58:10-FA22:6, and TAG60:10-FA22:6 decreased. For aged mice, we indicated that lipid components phosphatidic acid (PA) (18:1/20:2) and TAG52:5-FA20:4 in the sevoflurane group increased, but PE (14:0/22:4), diglyceride (DAG) (16:1/18:2), and lysophosphatidylcholine (LPC) (16:1) + AcO decreased. More deeply, sevoflurane anesthesia resulted in the presence of 70 specific lipids in mice and marmosets. The enriched lipid subclasses were mainly monoacylglycerophosphoethanolamines and five other subclasses.ConclusionSevoflurane caused slight changes in lipid metabolism both in the aged brain of marmosets and mice. However, the pathways of lipid metabolism were not affected. The effects of sevoflurane on lipid metabolism in aged brains may differ among species.
| S-EPMC9298509 | biostudies-literature
Project description:RNA sequencing analysis of macaque’s prefrontal cortex
2020-09-10 | GSE148437 | GEO
Project description:BackgroundEarly life stress (ELS) refers to exposure to negative childhood experiences, such as neglect, disaster, and physical, mental, or emotional abuse. ELS can permanently alter the brain, leading to cognitive impairment, increased sensitivity to future stressors, and mental health risks. The prefrontal cortex (PFC) is a key brain region implicated in the effects of ELS.MethodsTo better understand the effects of ELS on the PFC, we ran a meta-analysis of publicly available transcriptional profiling datasets. We identified five datasets (GSE89692, GSE116416, GSE14720, GSE153043, GSE124387) that characterized the long-term effects of multi-day postnatal ELS paradigms (maternal separation, limited nesting/bedding) in male and female laboratory rodents (rats, mice). The outcome variable was gene expression in the PFC later in adulthood as measured by microarray or RNA-Seq. To conduct the meta-analysis, preprocessed gene expression data were extracted from the Gemma database. Following quality control, the final sample size was n=89: n=42 controls & n=47 ELS: GSE116416 n=23 (no outliers); GSE116416 n=44 (2 outliers); GSE14720 n=7 (no outliers); GSE153043 n=9 (1 outlier), and GSE124387 n=6 (no outliers). Differential expression was calculated using the limma pipeline followed by an empirical Bayes correction. For each gene, a random effects meta-analysis model was then fit to the ELS vs. Control effect sizes (Log2 Fold Changes) from each study.ResultsOur meta-analysis yielded stable estimates for 11,885 genes, identifying five genes with differential expression following ELS (false discovery rate< 0.05): transforming growth factor alpha (Tgfa), IQ motif containing GTPase activating protein 3 (Iqgap3), collagen, type XI, alpha 1 (Col11a1), claudin 11 (Cldn11) and myelin associated glycoprotein (Mag), all of which were downregulated. Broadly, gene sets associated with oligodendrocyte differentiation, myelination, and brain development were downregulated following ELS. In contrast, genes previously shown to be upregulated in Major Depressive Disorder patients were upregulated following ELS.ConclusionThese findings suggest that ELS during critical periods of development may produce long-term effects on the efficiency of transmission in the PFC and drive changes in gene expression similar to those underlying depression.
| S-EPMC11601536 | biostudies-literature
Project description:Prolonged sitting is increasingly common and may possibly be unfavorable for cognitive function and mood. In this randomized crossover study, the effects of frequent, short physical activity breaks during prolonged sitting on cognitive task-related activation of the prefrontal cortex were investigated. The effects on working memory, psychological factors, and blood glucose were also examined, and whether arterial stiffness moderated prefrontal cortex activation. Thirteen subjects (mean age 50.5 years; eight men) underwent three 3-h sitting conditions, interrupted every 30-min by a different 3-min break on separate, randomized-ordered days: seated social interactions (SOCIAL), walking (WALK), or simple resistance activities (SRA). Arterial stiffness was assessed at baseline. Before and after each 3-h condition, psychological factors (stress, mood, sleepiness, and alertness) were assessed through questionnaires and functional near-infrared spectroscopy (fNIRS) was used to measure changes in prefrontal oxygenated hemoglobin (Oxy-Hb), indicative of cortical activation, while performing working memory tasks [1- (baseline), 2-, and 3-back]. Blood glucose levels were continuously measured throughout the conditions. Results revealed no significant changes in Oxy-Hb during the 2-back compared with the 1-back test in any condition, and no time-by-condition interactions. During the 3-back test, there was a significant decrease in Oxy-Hb compared with the 1-back after the WALK condition in the right prefrontal cortex, but there were no time-by-condition interactions, although 3-back reaction time improved only in the WALK condition. Mood and alertness improved after the WALK condition, which was significantly different from the SOCIAL condition. Arterial stiffness moderated the effects, such that changes in Oxy-Hb were significantly different between WALK and SOCIAL conditions only among those with low arterial stiffness. Blood glucose during the interventions did not differ between conditions. Thus, breaking up prolonged sitting with frequent, short physical activity breaks may reduce right prefrontal cortex activation, with improvements in some aspects of working memory, mood, and alertness. Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT04137211.
| S-EPMC8481573 | biostudies-literature
Project description:Simultaneous spike-counts of neural populations are typically modeled by a Gaussian distribution. On short time scales, however, this distribution is too restrictive to describe and analyze multivariate distributions of discrete spike-counts. We present an alternative that is based on copulas and can account for arbitrary marginal distributions, including Poisson and negative binomial distributions as well as second and higher-order interactions. We describe maximum likelihood-based procedures for fitting copula-based models to spike-count data, and we derive a so-called flashlight transformation which makes it possible to move the tail dependence of an arbitrary copula into an arbitrary orthant of the multivariate probability distribution. Mixtures of copulas that combine different dependence structures and thereby model different driving processes simultaneously are also introduced. First, we apply copula-based models to populations of integrate-and-fire neurons receiving partially correlated input and show that the best fitting copulas provide information about the functional connectivity of coupled neurons which can be extracted using the flashlight transformation. We then apply the new method to data which were recorded from macaque prefrontal cortex using a multi-tetrode array. We find that copula-based distributions with negative binomial marginals provide an appropriate stochastic model for the multivariate spike-count distributions rather than the multivariate Poisson latent variables distribution and the often used multivariate normal distribution. The dependence structure of these distributions provides evidence for common inhibitory input to all recorded stimulus encoding neurons. Finally, we show that copula-based models can be successfully used to evaluate neural codes, e.g., to characterize stimulus-dependent spike-count distributions with information measures. This demonstrates that copula-based models are not only a versatile class of models for multivariate distributions of spike-counts, but that those models can be exploited to understand functional dependencies.
| S-EPMC2776173 | biostudies-literature