Effect of both selenium and biosynthesized nanoselenium particles on cadmium-induced neurotoxicity in albino rats

2019 ◽  
Vol 39 (2) ◽  
pp. 159-172 ◽  
Author(s):  
MA Al Kahtani

Because cadmium (Cd) is not naturally degradable by ecosystems, it interferes with many types of food chains. Cd accumulates in the kidney, liver and in the nervous tissues, especially the brain. The neurotoxicity of Cd is very high, as it alters the integrity, and increases the permeability, of the blood–brain barrier. Cd penetrates and accumulates in neurons in the brains of rats. This study reveals that Cd decreases antioxidant enzymes and increases oxidative stress in the brain. In addition, Cd increases lipid peroxidation of brain tissues. Cd increases the expression of the Cu/Zn superoxide dismutase gene. It also affects cholinergic, glutamatergic, gamma-Aminobutyric acid (GABAergic), dopamine, serotonin and acetylcholine neurotransmitters in brain tissue. Consequently, Cd increases the formation of amyloid β, a neurotoxic index, and induces apoptosis by changing the quality and the quantity of Bcl-2, Bax and p53 proteins. In conclusion, both selenium and nanoselenium show potential antioxidant activity and promote recovery from the neurotoxic action of Cd.

2021 ◽  
Vol 22 (3) ◽  
pp. 1285
Author(s):  
Seong Soon Kim ◽  
Hyemin Kan ◽  
Kyu-Seok Hwang ◽  
Jung Yoon Yang ◽  
Yuji Son ◽  
...  

Epilepsy is one of the most common neurological disorders, and it is characterized by spontaneous seizures. In a previous study, we identified 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as a novel anti-epileptic agent in chemically- or genetically-induced epileptic zebrafish and mouse models. In this study, we investigated the anti-epileptic effects of GM-90432 through neurochemical profiling-based approach to understand the neuroprotective mechanism in a pentylenetetrazole (PTZ)-induced epileptic seizure zebrafish model. GM-90432 effectively improved PTZ-induced epileptic behaviors via upregulation of 5-hydroxytryptamine, 17-β-estradiol, dihydrotestosterone, progesterone, 5α -dihydroprogesterone, and allopregnanolone levels, and downregulation of normetanephrine, gamma-aminobutyric acid, and cortisol levels in brain tissue. GM-90432 also had a protective effect against PTZ-induced oxidative stress and zebrafish death, suggesting that it exhibits biphasic neuroprotective effects via scavenging of reactive oxygen species and anti-epileptic activities in a zebrafish model. In conclusion, our results suggest that neurochemical profiling study could be used to better understand of anti-epileptic mechanism of GM-90432, potentially leading to new drug discovery and development of anti-seizure agents.


2015 ◽  
Vol 96 (5) ◽  
pp. 806-810
Author(s):  
R V Deev ◽  
Yu M Shatrova ◽  
A I Sinitskiy ◽  
N S Molchanova ◽  
A K Yunusova ◽  
...  

Aim. To study the changes in levels of biogenic amines-neurotransmitters in the brain at experimental post-traumatic stress disorder development in rats. Methods. Post-traumatic stress disorder was modeled by keeping 48 outbred male rats in under constant and inescapable strong unconditioned stimulus. The control group included 16 intact animals, not exposed to stress influences. The levels of 3,4-dihydroxyphenylalanine, dopamine, norepinephrine, epinephrine and gamma-aminobutyric acid were determined by fluorometric methods. Behavioral activity of animals was evaluated on the day 3, 7, 10 and 14 by «open field» and «elevated plus maze» actinographs. Results. When comparing the concentrations of studied neurotransmitters in the brain of control animals with experimental groups, reflecting the development of post-traumatic stress disorder at the time, adrenaline and 3,4-dihydroxyphenylalanine levels were increased on the third day, level of norepinephrine was reduced on the seventh day, 3,4-dihydroxyphenylalanine, dopamine, norepinephrine levels were elevaled, gamma-aminobutyric acid level was reduced on the tenth day, gamma-aminobutyric acid level was increased on the fourteenth day after the stress. Conclusion. According to the results of the correlation analysis, the largest contribution to the development of behavioral disorders are made by altered brain level of gamma-aminobutyric acid at the time of post-traumatic stress disorder formation (tenth and fourteenth day). At the earlier stages (third and seventh day), the relationship of rats behavioral activity and altered 3,4-dihydroxyphenylalanine and norepinephrine brain levels was shown.


2009 ◽  
Vol 12 (1) ◽  
pp. 12-20 ◽  
Author(s):  
Evgeniya A. Zyablitseva ◽  
Nikolay S. Kositsyn ◽  
Galina I. Shul'gina

The research described here investigates the role played by inhibitory processes in the discriminations made by the nervous system of humans and animals between familiar and unfamiliar and significant and nonsignificant events. This research compared the effects of two inhibitory mediators of gamma-aminobutyric acid (GABA): 1) phenibut, a nonselective agonist of ionotropic GABAAand metabotropic GABABreceptors and 2) gaboxadol a selective agonist of ionotropic GABAAreceptors on the process of developing active defensive and inhibitory conditioned reflexes in alert non-immobilized rabbits. It was found that phenibut, but not gaboxadol, accelerates the development of defensive reflexes at an early stage of conditioning. Both phenibut and gaboxadol facilitate the development of conditioned inhibition, but the effect of gaboxadol occurs at later stages of conditioning and is less stable than that of phenibut. The earlier and more stable effects of phenibut, as compared to gaboxadol, on storage in memory of the inhibitory significance of a stimulus may occur because GABABreceptors play the dominant role in the development of internal inhibition during an early stage of conditioning. On the other hand this may occur because the participation of both GABAAand GABABreceptors are essential to the process. We discuss the polyfunctionality of GABA receptors as a function of their structure and the positions of the relevant neurons in the brain as this factor can affect regulation of various types of psychological processes.


2020 ◽  
Vol 12 ◽  
Author(s):  
Zequn Yin ◽  
Xuerui Wang ◽  
Shihong Zheng ◽  
Peichang Cao ◽  
Yuanli Chen ◽  
...  

Alzheimer’s disease (AD) is the most common form of dementia in the elderly. It may be caused by oxidative stress, inflammation, and cerebrovascular dysfunctions in the brain. LongShengZhi Capsule (LSZ), a traditional Chinese medicine, has been approved by the China Food and Drug Administration for treatment of patients with cardiovascular/cerebrovascular disease. LSZ contains several neuroprotective ingredients, including Hirudo, Astmgali Radix, Carthami Flos (Honghua), Persicae Semen (Taoren), Acori Tatarinowii Rhizoma (Shichangpu), and Acanthopanax Senticosus (Ciwujia). In this study, we aimed to determine the effect of LSZ on the AD process. Double transgenic mice expressing the amyloid-β precursor protein and mutant human presenilin 1 (APP/PS1) to model AD were treated with LSZ for 7 months starting at 2 months of age. LSZ significantly improved the cognition of the mice without adverse effects, indicating its high degree of safety and efficacy after a long-term treatment. LSZ reduced AD biomarker Aβ plaque accumulation by inhibiting β-secretase and γ-secretase gene expression. LSZ also reduced p-Tau expression, cell death, and inflammation in the brain. Consistently, in vitro, LSZ ethanol extract enhanced neuronal viability by reducing L-glutamic acid-induced oxidative stress and inflammation in HT-22 cells. LSZ exerted antioxidative effects by enhancing superoxide dismutase and glutathione peroxidase expression, reduced Aβ accumulation by inhibiting β-secretase and γ-secretase mRNA expression, and decreased p-Tau level by inhibiting NF-κB-mediated inflammation. It also demonstrated neuroprotective effects by regulating the Fas cell surface death receptor/B-cell lymphoma 2/p53 pathway. Taken together, our study demonstrates the antioxidative stress, anti-inflammatory, and neuroprotective effects of LSZ in the AD-like pathological process and suggests it could be a potential medicine for AD treatment.


Author(s):  
Juncai Pu ◽  
Yiyun Liu ◽  
Siwen Gui ◽  
Lu Tian ◽  
Yue Yu ◽  
...  

AbstractExtensive research has been carried out on the metabolomic changes in animal models of depression; however, there is no general agreement about which metabolites exhibit constant changes. Therefore, the aim of this study was to identify consistently altered metabolites in large-scale metabolomics studies of depression models. We performed vote counting analyses to identify consistently upregulated or downregulated metabolites in the brain, blood, and urine of animal models of depression based on 3743 differential metabolites from 241 animal metabolomics studies. We found that serotonin, dopamine, gamma-aminobutyric acid, norepinephrine, N-acetyl-L-aspartic acid, anandamide, and tryptophan were downregulated in the brain, while kynurenine, myo-inositol, hydroxykynurenine, and the kynurenine to tryptophan ratio were upregulated. Regarding blood metabolites, tryptophan, leucine, tyrosine, valine, trimethylamine N-oxide, proline, oleamide, pyruvic acid, and serotonin were downregulated, while N-acetyl glycoprotein, corticosterone, and glutamine were upregulated. Moreover, citric acid, oxoglutaric acid, proline, tryptophan, creatine, betaine, L-dopa, palmitic acid, and pimelic acid were downregulated, and hippuric acid was upregulated in urine. We also identified consistently altered metabolites in the hippocampus, prefrontal cortex, serum, and plasma. These findings suggested that metabolomic changes in depression models are characterized by decreased neurotransmitter and increased kynurenine metabolite levels in the brain, decreased amino acid and increased corticosterone levels in blood, and imbalanced energy metabolism and microbial metabolites in urine. This study contributes to existing knowledge of metabolomic changes in depression and revealed that the reproducibility of candidate metabolites was inadequate in previous studies.


1988 ◽  
Vol 251 (2) ◽  
pp. 559-562 ◽  
Author(s):  
P C Caron ◽  
L J Cote ◽  
L T Kremzner

Putrescine is the major source of gamma-aminobutyric acid (GABA) in the rat adrenal gland. Diamine oxidase, and not monoamine oxidase, is essential for GABA formation from putrescine in the adrenal gland. Aminoguanidine, a diamine oxidase inhibitor, decreases the GABA concentration in the adrenal gland by more than 70% after 4 h, and almost to zero in 24 h. Studies using [14C]putrescine confirm that [14C]GABA is the major metabolite of putrescine in the adrenal gland. Inhibition of GABA transaminase by amino-oxyacetic acid does not change the GABA concentration in the adrenal gland, as compared with the brain, where the GABA concentration rises. With aminoguanidine, the turnover time of GABA originating from putrescine in the adrenal gland is 5.6 h, reflecting a slower rate of GABA metabolism compared with the brain. Since GABA in the adrenal gland is almost exclusively derived from putrescine, the role of GABA may relate to the role of putrescine as a growth factor and regulator of cell metabolism.


2020 ◽  
Author(s):  
Cheng Wu ◽  
Yi-wei Feng ◽  
Qun Zhang ◽  
Feng-yin Liang ◽  
Yue Lan ◽  
...  

AbstractThe glymphatic system contributes to a large proportion of brain waste clearance, including removal of amyloid β (Aβ). We have demonstrated that glutamate and γ-aminobutyric acid (GABA) influence glymphatic clearance through distinct mechanisms whereby GABA exerts modulatory effects in an aquaporin-4 (AQP4)-dependent manner while the actions of glutamate are pulsation-dependent. The efficacy of GABA and glutamate in alleviating Aβ in APP-PS1 and Angiotensin-II (Ang-II) induced hypertension mouse models was further evaluated. Notably, increasing GABA or inhibiting glutamate levels led to reduced binding of Aβ to pre-labeled plaques to similar extents in APP-PS1 mice while GABA appeared more efficient in Aβ clearance in hypertensive animals than the glutamate inhibitor. Our findings support the modulation of neurotransmitters that influence the glymphatic pathway via distinct mechanisms as a potentially effective therapeutic strategy for clearance of Aβ deposits from the brain.


Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 620
Author(s):  
Seung Yeon Baek ◽  
Fu Yi Li ◽  
Da Hee Kim ◽  
Su Jin Kim ◽  
Mee Ree Kim

Enteromorpha prolifera, a green alga, has long been used in food diets as well as traditional remedies in East Asia. Our preliminary study demonstrated that an ethyl acetate extract of Enteromorpha prolifera (EAEP) exhibited the strongest antioxidant activity compared to ethanol or water extracts. Nonetheless, there has been no report on the effect of EAEP on memory impairment due to oxidative damage. This study investigated whether EAEP could attenuate memory deficits in an oxidative stress-induced mouse model. EAEP was orally administered (50 or 100 mg/kg body weight (b.w.)) to mice and then scopolamine was administered. The oral administration of EAEP at 100 mg/kg b.w. significantly restored memory impairments induced by scopolamine, as evaluated by the Morris water maze test, and the passive avoidance test. Further, EAEP upregulated the protein expression of BDNF, p-CREB, p-TrkB, and p-Akt. Moreover, EAEP downregulated the expression of amyloid-β, tau, and APP. The regulation of cholinergic marker enzyme activities and the protection of neuronal cells from oxidative stress-induced cell death in the brain of mice via the downregulation of amyloid-β and the upregulation of the BDNF/TrkB pathway by EAEP suggest its potential as a pharmaceutical candidate to prevent neurodegenerative diseases.


1973 ◽  
Vol 23 ◽  
pp. 73
Author(s):  
T. Matsuda ◽  
J.Y. Wu ◽  
E. Roberts

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