scholarly journals GABAA Receptor/STEP61 Signaling Pathway May Be Involved in Emulsified Isoflurane Anesthesia in Rats

2020 ◽  
Vol 21 (11) ◽  
pp. 4078 ◽  
Author(s):  
Xingkai Zhao ◽  
Guangjun Chang ◽  
Yan Cheng ◽  
Zhenlei Zhou

(1) Background: Emulsified isoflurane (EISO) is a type of intravenous anesthetic. How emulsified isoflurane works in the brain is still unclear. The aim of this study was to explore whether epigenetic mechanisms affect anesthesia and to evaluate the anesthetic effects of emulsified isoflurane in rats. (2) Methods: Rats were randomly divided into four groups (n = 8/group): The tail vein was injected with normal saline 0.1 mL·kg−1·min−1 for the control (Con) group, with intralipid for the fat emulsion (FE) group, with EISO at 60 mg·kg−1·min−1 for the high-concentration (HD) group, and 45 mg·kg−1·min−1 for the low-concentration (LD) group. The consciousness state, motor function of limbs, and response to nociceptive stimulus were observed after drug administration. (3) Results: Using real-time polymerase chain reaction (PCR) to assess the promoter methylation of ion channel proteins in the cerebral cortex of rats anesthetized by EISO, we demonstrated that the change in the promoters’ methylation of the coding genes for gamma-aminobutyric acid A receptor α1 subunit (GABAAα1), N-methyl-D-aspartate receptor subunit 1 (NMDAR1), and mu opioid receptor 1 (OPRM1) was accompanied by the change in messenger ribonucleic acid (mRNA) and protein expression by these genes. (4) Conclusion: These data suggest that the epigenetic factors’ modulation might offer a novel approach to explore the anesthetic mechanism of EISO.

Diabetes ◽  
1979 ◽  
Vol 28 (7) ◽  
pp. 629-633 ◽  
Author(s):  
H. Taniguchi ◽  
Y. Okada ◽  
H. Seguchi ◽  
C. Shimada ◽  
M. Seki ◽  
...  

Author(s):  
Sara Keränen ◽  
Santeri Suutarinen ◽  
Rahul Mallick ◽  
Johanna P. Laakkonen ◽  
Diana Guo ◽  
...  

Abstract Background Brain arteriovenous malformations (bAVM) may rupture causing disability or death. BAVM vessels are characterized by abnormally high flow that in general triggers expansive vessel remodeling mediated by cyclo-oxygenase-2 (COX2), the target of non-steroidal anti-inflammatory drugs. We investigated whether COX2 is expressed in bAVMs and whether it associates with inflammation and haemorrhage in these lesions. Methods Tissue was obtained from surgery of 139 bAVMs and 21 normal Circle of Willis samples. The samples were studied with immunohistochemistry and real-time quantitative polymerase chain reaction (RT-PCR). Clinical data was collected from patient records. Results COX2 expression was found in 78% (109/139) of the bAVMs and localized to the vessels’ lumen or medial layer in 70% (95/135) of the bAVMs. Receptors for prostaglandin E2, a COX2-derived mediator of vascular remodeling, were found in the endothelial and smooth muscle cells and perivascular inflammatory cells of bAVMs. COX2 was expressed by infiltrating inflammatory cells and correlated with the extent of inflammation (r = .231, p = .007, Spearman rank correlation). COX2 expression did not associate with haemorrhage. Conclusion COX2 is induced in bAVMs, and possibly participates in the regulation of vessel wall remodelling and ongoing inflammation. Role of COX2 signalling in the pathobiology and clinical course of bAVMs merits further studies.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 530
Author(s):  
Oliviero Bruni ◽  
Luigi Ferini-Strambi ◽  
Elena Giacomoni ◽  
Paolo Pellegrino

Sleep is an essential component of physical and emotional well-being, and lack, or disruption, of sleep due to insomnia is a highly prevalent problem. The interest in complementary and alternative medicines for treating or preventing insomnia has increased recently. Centuries-old herbal treatments, popular for their safety and effectiveness, include valerian, passionflower, lemon balm, lavender, and Californian poppy. These herbal medicines have been shown to reduce sleep latency and increase subjective and objective measures of sleep quality. Research into their molecular components revealed that their sedative and sleep-promoting properties rely on interactions with various neurotransmitter systems in the brain. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that plays a major role in controlling different vigilance states. GABA receptors are the targets of many pharmacological treatments for insomnia, such as benzodiazepines. Here, we perform a systematic analysis of studies assessing the mechanisms of action of various herbal medicines on different subtypes of GABA receptors in the context of sleep control. Currently available evidence suggests that herbal extracts may exert some of their hypnotic and anxiolytic activity through interacting with GABA receptors and modulating GABAergic signaling in the brain, but their mechanism of action in the treatment of insomnia is not completely understood.


Author(s):  
Lisa Marie Anderson-Umana

The problems related to Sunday school students not making the connection between Scripture and daily life and a superficial teaching of the Bible compelled the author to create a novel approach to teaching Sunday school called the “Good Sower.” The imagery of a “Good Sower” is used to teach volunteers how to teach the Bible. Based on solid research regarding how the brain learns, it serves as an overlay in conjunction with published curriculum.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Safia Akhtar ◽  
Silas A. Culver ◽  
Helmy M. Siragy

AbstractRecent studies suggested that renal gluconeogenesis is substantially stimulated in the kidney in presence of obesity. However, the mechanisms responsible for such stimulation are not well understood. Recently, our laboratory demonstrated that mice fed high fat diet (HFD) exhibited increase in renal Atp6ap2 [also known as (Pro)renin receptor] expression. We hypothesized that HFD upregulates renal gluconeogenesis via Atp6ap2-PGC-1α and AKT pathway. Using real-time polymerase chain reaction, western blot analysis and immunostaining, we evaluated renal expression of the Atp6ap2 and renal gluconeogenic enzymes, PEPCK and G6Pase, in wild type and inducible nephron specific Atp6ap2 knockout mice fed normal diet (ND, 12 kcal% fat) or a high-fat diet (HFD, 45 kcal% fat) for 8 weeks. Compared with ND, HFD mice had significantly higher body weight (23%) (P < 0.05), renal mRNA and protein expression of Atp6ap2 (39 and 35%), PEPCK (44 and 125%) and G6Pase (39 and 44%) respectively. In addition, compared to ND, HFD mice had increased renal protein expression of PGC-1α by 32% (P < 0.05) and downregulated AKT by 33% (P < 0.05) respectively in renal cortex. Atp6ap2-KO abrogated these changes in the mice fed HFD. In conclusion, we identified novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway.


1967 ◽  
Vol 45 (6) ◽  
pp. 853-861 ◽  
Author(s):  
W. Thompson

The hydrolysis of monophosphoinositide by soluble extracts from rat brain is described. Diglyceride and inositol monophosphate are liberated along with a small amount of free fatty acids. Hydrolysis of the lipid is optimal at pH 5.4 in acetate buffer. The reaction is stimulated by calcium ions or by high concentration of monovalent cations and, to a less extent, by long-chain cationic amphipathic compounds. Enzyme activity is lost on dialysis of the brain extract and can be restored by diffusible factor(s). Some differences in the conditions for hydrolysis of mono- and tri-phosphoinositides are noted.


1998 ◽  
Vol 26 (1) ◽  
pp. 1-12 ◽  
Author(s):  
H Saito ◽  
T Yanaihara

For preventing the reduction of bone mass in post-menopausal women, oestrogen replacement is known to be useful and the importance of sex steroids in bone metabolism in both sexes is well established. The presence of steroid-converting-enzyme activities in various osteoblast and osteoblast-like cells has been demonstrated using in vitro culture systems. In the present study, we assessed the expression of messenger ribonucleic acid (mRNA) for aromatase, steroid sulphatase, 5α-reductase, 17β-hydroxysteroid dehydrogenase (17β-HSD) and 3β-HSD by reverse transcription-polymerase chain reaction in the human osteoblast-like cell lines, MG 63 and HOS. Oestrogen, androgen and progesterone receptor mRNAs were also measured. Expression of mRNA for these enzymes and receptors was found in both cell lines without induction. From these and previous findings, we conclude that osteoblast-like cells have the capacity to form biologically potent oestrogens and androgens from peripheral circulating steroids. This may indicate an important role of bone in facilitating hormonal action.


1993 ◽  
Vol 70 (5) ◽  
pp. 1741-1758 ◽  
Author(s):  
F. R. Robinson ◽  
A. Straube ◽  
A. F. Fuchs

1. We studied the effect of temporarily inhibiting neurons in the caudal fastigial nucleus in two rhesus macaques trained to make saccades to jumping targets. We placed injections of the gamma-aminobutyric acid (GABA) agonist muscimol unilaterally or bilaterally at sites in the caudal fastigial nucleus where we had recorded saccade-related neurons a few minutes earlier. 2. Unilateral injections (n = 9) made horizontal saccades to the injected side hypermetric and those to the other side hypometric (mean gain of 1.37 and 0.61, respectively, for 10 degrees target steps, and 1.26 and 0.81 for 20 degrees target steps; normal saccade gain was 0.96). Saccades to vertical targets showed a small but significant hypermetria and curved strongly toward the side of the injection. The trajectories and end points of all targeted saccades were more variable than normal. 3. After unilateral injections, centripetal saccades were slightly larger than centrifugal saccades (mean gains for ipsilateral saccades were 1.42 and 1.31, respectively, for 10 degrees target steps, and 1.37 and 1.15 for 20 degrees target steps). 4. Unilateral injections increased the average acceleration of ipsilateral saccades and decreased the acceleration of contralateral saccades. Injections decreased both the acceleration and deceleration of vertical saccades. 5. After dysmetric saccades, monkeys acquired the target with an abnormally high number of hypometric corrective saccades. Injection increased the average number of corrective saccades from 0.6 to 2.1 after 10 degrees horizontal target steps and from 0.8 to 2.1 after 20 degrees steps. The size of each successive corrective saccade in a series decreased, and the latency from the previous corrective saccade increased. 6. Bilateral injections (n = 2) of muscimol, in which we injected first into the left caudal fastigial nucleus and then, within 30 min, into the right, made all saccades hypermetric (mean gain for 10 degrees right, left, up, and down saccades was 1.18, 1.49, 1.43, and 1.10, respectively). Paradoxically, bilateral injection decreased both saccade acceleration and deceleration. Saccade trajectories and end points were more variable than normal. 7. To account for the effects of our injections, we propose that the activity of caudal fastigial neurons on one side normally helps to decelerate ipsilateral saccades and helps to accelerate contralateral saccades by influencing the feedback loop of the saccade burst generator in the brain stem. Without caudal fastigial activity the brain stem burst generator produces hypermetric, variable saccades. We therefore also propose that the influence of caudal fastigial neurons on the burst generator makes saccades more consistent and accurate.(ABSTRACT TRUNCATED AT 400 WORDS)


2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Xinxin Yang ◽  
Haibo Yang ◽  
Fengdi Wu ◽  
Zhipeng Qi ◽  
Jiashuo Li ◽  
...  

Excessive manganese (Mn) can accumulate in the striatum of the brain following overexposure. Oxidative stress is a well-recognized mechanism in Mn-induced neurotoxicity. It has been proven that glutathione (GSH) depletion is a key factor in oxidative damage during Mn exposure. However, no study has focused on the dysfunction of GSH synthesis-induced oxidative stress in the brain during Mn exposure. The objective of the present study was to explore the mechanism of Mn disruption of GSH synthesis via EAAC1 and xCT in vitro and in vivo. Primary neurons and astrocytes were cultured and treated with different doses of Mn to observe the state of cells and levels of GSH and reactive oxygen species (ROS) and measure mRNA and protein expression of EAAC1 and xCT. Mice were randomly divided into seven groups, which received saline, 12.5, 25, and 50 mg/kg MnCl2, 500 mg/kg AAH (EAAC1 inhibitor) + 50 mg/kg MnCl2, 75 mg/kg SSZ (xCT inhibitor) + 50 mg/kg MnCl2, and 100 mg/kg NAC (GSH rescuer) + 50 mg/kg MnCl2 once daily for two weeks. Then, levels of EAAC1, xCT, ROS, GSH, malondialdehyde (MDA), protein sulfhydryl, carbonyl, 8-hydroxy-2-deoxyguanosine (8-OHdG), and morphological and ultrastructural features in the striatum of mice were measured. Mn reduced protein levels, mRNA expression, and immunofluorescence intensity of EAAC1 and xCT. Mn also decreased the level of GSH, sulfhydryl, and increased ROS, MDA, 8-OHdG, and carbonyl in a dose-dependent manner. Injury-related pathological and ultrastructure changes in the striatum of mice were significantly present. In conclusion, excessive exposure to Mn disrupts GSH synthesis through inhibition of EAAC1 and xCT to trigger oxidative damage in the striatum.


1999 ◽  
Vol 57 (3B) ◽  
pp. 753-760 ◽  
Author(s):  
TEREZINHA DE JESUS T. SANTOS ◽  
CARLOS M. DE CASTRO-COSTA ◽  
SÍLVIO D. A. GIFFONI ◽  
FRANKLIN J. C. SANTOS ◽  
RODRIGO S. N. RAMOS ◽  
...  

Baclofen (beta-p-chlorophenyl-GABA) has been used in humans to treat spasticity, as well as trigeminal neuralgia. Since GABA (gamma-aminobutyric acid) has been implicated in inhibitory and analgesic effects in the nervous system, it was of interest to study the effect of baclofen in experimental neuropathic pain. With this purpose, experiments were carried out in 17 neuropathic rats with constrictive sciatic injury, as described by Bennet and Xie (1988), taking as pain parameters scratching behaviour and the latency to the thermal nociceptive stimulus. The results showed that baclofen induces, in a dose-dependent manner, significant decrease (p < 0.05) of scratching behaviour and significant increase (p < 0.05) of the latency to the nociceptive thermal stimulus. The absence of antagonism of naloxone suggested a non-participation of an opioid-mediated mechanism in this analgesic effect of baclofen on experimental neuropathic pain.


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