scholarly journals Isoliquiritigenin Alleviates Semen Strychni-Induced Neurotoxicity by Restoring the Metabolic Pathway of Neurotransmitters in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Lu Wang ◽  
Min Zhang ◽  
Jing Wen ◽  
Yalan Xiang ◽  
Xiaoyu Duan ◽  
...  
Keyword(s):  
Metabolic Pathway ◽  
Neuronal Degeneration ◽  
Acute Poisoning ◽  
Gamma Aminobutyric Acid ◽  
Methyl Transferase ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Acid Type ◽  
Acute Neurotoxicity ◽  
Semen Strychni

Acute neurotoxicity of Semen Strychni can result in sudden death in epilepsy. The detoxification method and mechanism of Semen Strychni acute poisoning have not been clarified. This experiment focused on the mechanism of Semen Strychni neurotoxicity and the alleviation effects of isoliquiritigenin. The rats were intraperitoneally injected with Semen Strychni extract (125 mg/kg), followed by oral administration of isoliquiritigenin (50 mg/kg) for 7 days. FJ-B staining was used to evaluate the degree of injury on hippocampus neurons. The concentration of monoamines, amino acids, and choline neurotransmitters, the Dopamine (DA) and 5-hydroxytryptamine (5-HT) metabolic pathway in the hippocampus, cerebellum, striatum, prefrontal cortex, hypothalamus, serum, and plasma were detected by LC-MS/MS. The expression of neurotransmitter metabolic enzymes [catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO)] and neurotransmitter receptors [glutamate N-methyl-D-aspartic acid receptors (NMDARs) and gamma-aminobutyric acid type A receptor (GABRs)] were, respectively determined using ELISA and qRT-PCR. The results indicated that Semen Strychni induced neuronal degeneration in the hippocampal CA1 region. Meanwhile, Semen Strychni inhibited the mRNA expression of NMDAR1, NMDAR2A, NMDAR2B, GABRa1, GABRb2 and reduced the level of MAO, which disrupted the DA and 5-HT metabolic pathway. However, isoliquiritigenin reversed these effects. In summary, isoliquiritigenin showed alleviation effects on Semen Strychni-induced neurotoxicity, which could be attributed to restoring neurotransmitters metabolic pathway, most likely through the activation of NMDA receptors.

Role of Lacosamide in Preventing Pentylenetetrazole Kindling-Induced Alterations in the Expression of the Gamma-2 Subunit of the GABAA Receptor in Rats

2020 ◽  
Vol 13 (3) ◽  
pp. 251-260 ◽  
Author(s):  
Zsolt Gáll ◽  
Krisztina Kelemen ◽  
István Mihály ◽  
Pál Salamon ◽  
Ildikó Miklóssy ◽  
...  
Keyword(s):  
Gabaa Receptors ◽  
Immunofluorescent Staining ◽  
Gamma Aminobutyric Acid ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Voltage Gated Sodium Channels ◽  
Gene And Protein Expression ◽  
Gabaergic Synapses ◽  
Neuroprotective Actions ◽  
Generalized Epilepsy

Background: Epilepsy remains challenging to treat still no etiologic treatment has been identified, however, some antiepileptic drugs (AEDs) are able to modify the pathogenesis of the disease. Lacosamide (LCM) has been shown to possess complex anticonvulsant and neuroprotective actions, being an enhancer of the slow inactivation of voltage-gated sodium channels, and it has the potential to prevent epileptogenesis. Recent evidence has shown that LCM indirectly improves the function of GABAA receptors. Receptors at most GABAergic synapses involve the gamma-2 subunit, which contributes to both phasic and tonic inhibition, and its presence assures benzodiazepine sensitivity. Moreover, mutant gamma-2 subunits were associated with generalized epilepsy syndromes. In animal models, the expression of the gamma-2 subunit of the gamma-aminobutyric acid A receptor (GABAAg2) was shown to be increased in pentylenetetrazole (PTZ)-induced chemical kindling in Wistar rats. Objective: This study hypothesized that LCM might affect the kindling process by influencing the expression of GABAA receptors in the hippocampus. Methods: The gene and protein expression levels of the GABAAg2 were studied using RT-qPCR and immunofluorescent staining. Results: It was found that LCM treatment (10 mg/kg i.p. daily for 57 days) reduced the maximal intensity of the PTZ-induced seizures but did not prevent kindling. On the other hand, LCM treatment reverted the increase of mRNA expression of GABAAg2 in the hippocampus and prevented the decrease of GABAAg2 protein in the hippocampal CA1 region. Conclusion: LCM could exhibit modulatory effects on the GABAergic system of the hippocampus that may be independent of the anticonvulsant action.

scholarly journals Protective Effect of a Prosaposin-Derived, 18-Mer Peptide on Slowly Progressive Neuronal Degeneration after Brief Ischemia

2001 ◽  
Vol 21 (11) ◽  
pp. 1295-1302 ◽  
Author(s):  
Fumio Morita ◽  
Tong-Chun Wen ◽  
Junya Tanaka ◽  
Ryuji Hata ◽  
Junzo Desaki ◽  
...  
Keyword(s):  
Neuronal Degeneration ◽  
Neuronal Damage ◽  
Avoidance Task ◽  
Ca1 Neurons ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1 Neurons ◽  
Saposin C ◽  
Hippocampal Ca1

Slowly progressive degeneration of the hippocampal CA1 neurons was induced by 3-minute transient global ischemia in gerbils. Sustained degeneration of hippocampal CA1 neurons was evident 1 month after ischemia. To investigate the effects of an 18-mer peptide comprising the hydrophilic sequence of the rat saposin C domain (18MP) on this sustained neuronal degeneration, an intracerebroventricular 18MP infusion was initiated 3 days after ischemia. Histopathologic and behavior evaluations were conducted 1 week and 1 month after induction of ischemia. When compared with the vehicle infusion, 18MP treatment significantly increased the response latency time in a passive avoidance task. Increased neuronal density was also evident, as was the number of intact synapses in the hippocampal CA1 region at 1 week and 1 month after ischemia. 18MP treatment also significantly decreased the number of TUNEL-positive CA1 neurons 1 week after ischemia. Subsequent in vitro experiments using cultured neurons demonstrated that the 18MP at optimal extracellular concentrations of 1 to 100 fg/mL prevented nitric oxide–induced neuronal damage as expected and significantly up-regulated the expressions of bcl-xL mRNA and its translated protein. These results suggest that the gerbil model of 3-minute ischemia is useful in studying the pathogenesis of slowly progressive neuronal degeneration after stroke and in evaluating effects of novel therapeutic agents. It is likely that the 18MP at low extracellular concentrations prevents neuronal apoptosis possibly through up-regulation of the mitochondrial antiapoptotic factor Bcl-xL.

Cardiovascular Complications of Sleep Disorders: A Better Night’s Sleep for a Healthier Heart / From Bench to Bedside

2020 ◽  
Vol 19 (2) ◽  
pp. 210-232 ◽  
Author(s):  
Theodora A. Manolis ◽  
Antonis A. Manolis ◽  
Evdoxia J. Apostolopoulos ◽  
Helen Melita ◽  
Antonis S. Manolis
Keyword(s):  
Sleep Disorders ◽  
Disease Risk ◽  
Behavioral Therapy ◽  
Benzodiazepine Receptor ◽  
Cardiovascular Complications ◽  
Gamma Aminobutyric Acid ◽  
Acid Type ◽  
Increased Risk ◽  
Cv Disease ◽  
Meta Analyses

: Sleep is essential to and an integral part of life and when lacking or disrupted, a multitude of mental and physical pathologies ensue, including cardiovascular (CV) disease, which increases health care costs. Several prospective studies and meta-analyses show that insomnia, short (<7h) or long (>9h) sleep and other sleep disorders are associated with an increased risk of hypertension, metabolic syndrome, myocardial infarction, heart failure, arrhythmias, CV disease risk and/or mortality. The mechanisms by which insomnia and other sleep disorders lead to increased CV risk may encompass inflammatory, immunological, neuro-autonomic, endocrinological, genetic and microbiome perturbations. Guidelines are emerging that recommend a target of >7 h of sleep for all adults >18 years for optimal CV health. Treatment of sleep disorders includes cognitive-behavioral therapy considered the mainstay of non-pharmacologic management of chronic insomnia, and drug treatment with benzodiazepine receptor agonists binding to gamma aminobutyric acid type A (benzodiazepine and non-benzodiazepine agents) and some antidepressants. However, observational studies and meta-analyses indicate an increased mortality risk of anxiolytics and hypnotics, although bias may be involved due to confounding and high heterogeneity in these studies. Nevertheless, it seems that the risk incurred by the non-benzodiazepine hypnotic agents (Z drugs) may be relatively less than the risk of anxiolytics, with evidence indicating that at least one of these agents, zolpidem, may even confer a lower risk of mortality in adjusted models. All these issues are herein reviewed.

[11C]Flumazenil Positron Emission Tomography Analyses of Brain Gamma-Aminobutyric Acid Type A Receptors in Angelman Syndrome

2008 ◽  
Vol 152 (4) ◽  
pp. 546-549.e3 ◽  
Author(s):  
Naoko Asahina ◽  
Tohru Shiga ◽  
Kiyoshi Egawa ◽  
Hideaki Shiraishi ◽  
Shinobu Kohsaka ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Angelman Syndrome ◽  
Type A ◽  
Emission Tomography ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Positron Emission ◽  
Acid Type
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