Showing papers in "Metabolic Brain Disease in 2022"
TL;DR: In this paper , the authors investigated the role of CARV on the activation of TRPM2 and TRPV4 in SH-SY5Y neuronal, BV-2 microglial, and HEK293 cells.
Abstract: The overload cytosolic free Ca2+ (cCa2+) influx-mediated excessive generation of oxidative stress in the pathophysiological conditions induces neuronal and cellular injury via the activation of cation channels. TRPM2 and TRPV4 channels are activated by oxidative stress, and their specific antagonists have not been discovered yet. The antioxidant and anti-Covid-19 properties of carvacrol (CARV) were recently reported. Hence, I suspected possible antagonist properties of CARV against oxidative stress (OS)/ADP-ribose (ADPR)-induced TRPM2 and GSK1016790A (GSK)-mediated TRPV4 activations in neuronal and kidney cells. I investigated the antagonist role of CARV on the activations of TRPM2 and TRPV4 in SH-SY5Y neuronal, BV-2 microglial, and HEK293 cells. The OS/ADPR and GSK in the cells caused to increase of TRPM2/TRPV4 current densities and overload cytosolic free Ca2+ (cCa2+) influx with an increase of mitochondrial membrane potential, cytosolic (cROS), and mitochondrial (mROS) ROS. The changes were not observed in the absence of TRPM2 and TRPV4 or the presence of Ca2+ free extracellular buffer and PARP-1 inhibitors (PJ34 and DPQ). When OS-induced TRPM2 and GSK-induced TRPV4 activations were inhibited by the treatment of CARV, the increase of cROS, mROS, lipid peroxidation, apoptosis, cell death, cCa2+ concentration, caspase -3, and caspase -9 levels were restored via upregulation of glutathione and glutathione peroxidase. In conclusion, the treatment of CARV modulated the TRPM2 and TRPV4-mediated overload Ca2+ influx and may provide an avenue for protecting TRPM2 and TRPV4-mediated neurodegenerative diseases associated with the increase of mROS and cCa2+. The possible TRPM2 and TRPV4 blocker action of carvacrol (CARV) via the modulation oxidative stress and apoptosis in the SH-SY5Y neuronal cells. TRPM2 is activated by DNA damage-induced (via PARP-1 activation) ADP-ribose (ADPR) and reactive oxygen species (ROS) (H2O2), although it is inhibited by nonspecific inhibitors (ACA and 2-APB). TRPV4 is activated by the treatments of GSK1016790A (GSK), although it is inhibited by a nonspecific inhibitor (ruthenium red, RuRe). The treatment of GSK induces excessive generation of ROS. The accumulation of free cytosolic Ca2+ (cCa2+) via the activations of TRPM2 and TRPV4 in the mitochondria causes the increase of mitochondrial membrane depolarization (ΔΨm). In turn, the increase of ΔΨm causes the excessive generation of ROS. The TRPM2 and TRPV4-induced the excessive generations of ROS result in the increase of apoptosis and cell death via the activations of caspase -3 (Casp-3) and caspase -9 (Casp-9) in the neuronal cells, although their oxidant actions decrease the glutathione (GSH) and glutathione peroxidase (GSHPx) levels. The oxidant and apoptotic adverse actions of TRPM2 and TRPV4 are modulated by the treatment of CARV.
17 citations
TL;DR: The mechanisms by which a reactive gliosis can induce or contribute to the development and progression of AD are reviewed.
12 citations
TL;DR: The consensus of the literature search was that SA treatment may help neurological dysfunction or behavioral impairments management with antioxidant, anti-inflammatory properties and administration and proper dose of SA could be crucial factors for the effective treatment of neurological diseases.
12 citations
TL;DR: This first study regulate maternal gut microbiota and fetal neurodevelopment processes by using probiotics such as Bifidobacterium bifidum (BIF) and Lactobacillus salivarius (LAC) in the prenatal period to shed light on new therapeutic strategies for the impact of the use of probiotics on the neurodevelopmental processes of the neonatal processes.
11 citations
TL;DR: Capsaicin showed a concentration-dependent anti-proliferative effects in U87-MG and U251 cells, and might be used as a potential anticancer agent with ferroptosis-induced anti-Proliferatives effects in the treatment of human glioblastoma.
11 citations
TL;DR: Conclusively, BMSC-released exosomes might carry long noncoding RNA ZFAS1 to curb oxidative stress and inflammation related to ischemic stroke, which was possibly realized through miR-15a-5p inhibition.
10 citations
TL;DR: The methods of network pharmacology and molecular docking are used to analyze the effective monomer components of pinellia and reveal the involved signaling pathways to produce antidepressant effects.
10 citations
10 citations
TL;DR: Inhibition of Kv channels by these AChE inhibitors can generate neuroprotective effects by either mitigating Aβ toxicity and neuronal apoptosis, or facilitating cell proliferation, meaning that Kv channel is a promising candidate target for novel drugs for AD therapy.
9 citations
TL;DR: It was observed that co-treatment with 18β-GA at a dose of 50 and 100 mg/kg considerably ameliorated oxidative stress, inflammation, apoptosis, ER stress and JAK1/STAT1 signaling pathway in brain tissue.
9 citations
TL;DR: Sanguisorba minor (S. minor) has neuroprotective and antioxidant activities as discussed by the authors , however, its potential benefits in ameliorating learning and memory functions have been explored in no studies up to now.
Abstract: Sanguisorba minor (S. minor) has neuroprotective and antioxidant activities. However, its potential benefits in ameliorating learning and memory functions have been explored in no studies up to now. So, in the current study, rats were treated with S. minor hydro-ethanolic extract (50, 100, and 200 mg/kg, intraperitoneal (i.p.)) as well as rivastigmine (0.5 mg/kg, i.p.) for 21 consecutive days. Thereafter, their behavioral performance was assessed using Morris water maze (MWM) and passive avoidance (PA) tasks. Notably, 30 min before conducting the tasks, scopolamine was injected. Finally, the biochemical assessments were done using the brain tissue. The extract characterization was performed by liquid chromatography-mass spectrometry, which confirmed the presence of quercetin, myricetin, kaempferol, catechin, ellagic acid, and gallic acid derivatives. In the MWM test, the extract reduced both escape latency and the travelled distance, compared to the scopolamine group. Moreover, in the PA test, the latency to enter the dark chamber significantly increased by the extract, compared to the scopolamine group (p < 0.05-p < 0.001). Notably, the beneficial effects of S. minor on cognitive performance of the scopolamine-treated rats appeared to be similar or even better than rivastigmine in behavior performance. Similar to rivastigmine, it was observed that the extract attenuated both AChE activity and oxidative injury in the brain as evidenced by the increased antioxidant enzymes and total thiol content; however, it decreased malondialdehyde level (p < 0.05-p < 0.001). In conclusion, the results suggested the effectiveness of S. minor in preventing cognitive dysfunction induced by scopolamine. Accordingly, these protective effects might be produced by the regulation of cholinergic activity and oxidative stress. S. minor could be considered as a potential alternative therapy in cognition disorders.
TL;DR: This review presents the strengths and limitations of current metabolomic studies on IS, providing a reference for future related studies and reviews the application of animal models in metabolomic analyses aimed at investigating potential mechanisms of IS and developing novel therapeutic approaches.
TL;DR: An overview of the validation level and usage of psychometric tests used to detect MHE: Portosystemic hepatic encephalopathy test, continuous reaction time test, Stroop EncephalApp, animal naming test, critical flicker frequency test, and inhibitory control test is created.
TL;DR: The present review has tried to highlight how sirtuins are interlinked with Nrf2 and NF-κB and put forth how SIRT activators could serve as potential therapy for DPN.
TL;DR: LncRNA NEAT1 stabilizes Mfn2 mRNA via recruiting Nova, therefore increase the expression of Mfn 2 and alleviates ischemia-reperfusion induced oxidative stress and apoptosis via Mfn1/Sirt3 pathway.
TL;DR: AM provided neuroprotection by ameliorating the rotenone-induced α-Syn accumulation through AMPK-dependent autophagy activation and it can be considered as a therapeutic agent which might be having a higher translational value in the treatment of PD.
TL;DR: Results demonstrated that SAL inhibited oxidative stress through Nrf2/Trx1 signaling pathway, and subsequently reduced CIRI-induced apoptosis by inhibiting ASK1/MAPK.
TL;DR: RXRγ-mediated transcriptional activation of GPX4 might inhibit ferroptosis during I/R-induced brain injury, and this study aims to explore the regulatory effect and mechanism of retinoid X receptor γ on cerebral ischemia-reperfusion (I/R) injury.
TL;DR: In this paper , the authors summarized the most up-to-date understanding of the BBB and the cerebrospinal fluid acquired during the development of therapeutics for neuronopathic LSDs, and highlighted some of the associated challenges that require further research.
Abstract: Whereas significant strides have been made in the treatment of lysosomal storage diseases (LSDs), the neuronopathy associated with these diseases remains impervious mainly because of the blood-brain barrier (BBB), which prevents delivery of large molecules to the brain. However, 100 years of research on the BBB since its conceptualization have clarified many of its functional and structural characteristics, spurring recent endeavors to deliver therapeutics across it to treat central nervous system (CNS) disorders, including neuronopathic LSDs. Along with the BBB, the cerebrospinal fluid (CSF) also functions to protect the microenvironment of the CNS, and it is therefore deeply involved in CNS disorders at large. Recent research aimed at developing therapeutics for neuronopathic LSDs has uncovered a number of critical roles played by the CSF that require further clarification. This review summarizes the most up-to-date understanding of the BBB and the CSF acquired during the development of therapeutics for neuronopathic LSDs, and highlights some of the associated challenges that require further research.
TL;DR: The data indicate that chronic inhibition of BRD4 significantly restores memory impaired by amyloid β partly via CREB signaling and upregulating synaptic proteins of PSD95 and synaptophysin and reduces CREB/PSD95/synaptophysins levels in hippocampus.
TL;DR: Ginkgolide B exerted a neuroprotective effect on the cognitive function of SAMP8 mice by suppressing the activation of NLRP3 inflammasome via autophagic degradation and this effect was dependent on autophagy.
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TL;DR: Evidence is provided of an altered plasma exosomal circRNA expression profile and its potential function in IS and ideas for studying potential diagnostic biomarkers and therapeutic targets for IS are provided.
TL;DR: Results show that the NaHS effect on CBS and CSE protein expression is observed in a time- and tissue-dependent manner with no effect on 3-MST expression, which may suggest a potential role of H2S synthesis in hypothalamus and brainstem impairments observed after TBI.
TL;DR: To explore the functions of circRNA cyclin B1 in glioma and its possible mechanisms,Murine xenograft model assay was used for the role of circCCNB1 in vivo and the molecule relationships were analyzed by RIP, dual-luciferase reporter and RNA pull-down assays.
TL;DR: In this article , the effects of E2 on body composition and energy balance in young intact and ovariectomized (OVX) mice were compared to the aged animals treated with E2.
Abstract: Aging and menopause effect on body composition and energy balance. Estrogen (E2) plays an important role in body's metabolism. The aim of the present study was to determine changes in leptin function in young intact and ovariectomized (OVX) animals in comparison to the aged animals treated with E2. Young (Intact and OVX 4 months) and aged (19-21 months) female mice were fed High-fat diet (HFD) for 12 weeks and, then they were divided into eight groups including: Intact + OIL, Intact + E2, Intact + Pair body weight (PBW), OVX + OIL, OVX + E2, OVX + PBW, Aged + OIL, and Aged + E2. E2 was administered subcutaneously every four days for four weeks. Responsiveness to leptin was assessed by measuring energy balance components. Results showed that eating HFD increased weight and calorie consumption in young mice, and chronic treatment with E2 decreased both these variables in young animals. E2 only improved the sensitivity to leptin in young animals. Treatment with E2 resulted in increased α-MSH neuropeptide, reduced NPY and AgRP neuropeptides in the brain, and decreased serum leptin in the young animals. Also, treatment with E2 increased the expression of p-STAT3 molecular level in the hypothalamic arcuate nucleus (ARC) in the young animals. Our results indicated that response to E2 depended on age and E2 protects young HFD fed mice from obesity and improves leptin sensitivity.
TL;DR: The present review mainly focuses on the expression and activities of the circRNAs in the post-mortem brain, peripheral blood, and exosomes and gives an insight into the role of circRNA interaction with RNA binding proteins (RBPs) and nucleotide modification and their therapeutic potential in the context of schizophrenia.