scholarly journals Cannabidiol Modulates the Expression of Neurotrophin Signaling Pathway in Chronic Exposure Methamphetamine Rats During Abstinence Period

2021 ◽  
pp. 1-23
Author(s):  
Yasaman Razavi ◽  
◽  
Mohammad Najafi ◽  
Abbas Haghparast ◽  
Fariborz Keyhanfar ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Signaling Pathway ◽  
Chronic Exposure ◽  
Mrna Level ◽  
Neuropsychiatric Disorders ◽  
Control Group ◽  
Hippocampal Damage ◽  
Neuroprotective Effects ◽  
Neurotrophin Signaling ◽  
Abstinence Period

Several neuropsychiatric disorders such as addiction have indicated variations in the levels of neurotrophic factors. As an extremely addictive stimulant, Methamphetamine (METH) is associated with rising levels of abuse on a global scale. We have recently demonstrated that repeated intracerebroventricular (ICV) of cannabidiol (CBD), the most important non-psychotomimetic compound, can lead to diminished impairing memory and hippocampal damage caused by chronic exposure METH (CEM) in rats over the abstinence period. Furthermore, the results indicated a possible contribution of the neurotrophin signaling pathway (NSP) in regulating neurogenesis and survival. The next study was intended to evaluate whether these remained effects as measured in molecular pathway after abstinence period. In this regard, animals were given 2 mg/kg METH twice daily for a 10-day period. Then, we adopted real-time polymerase chain reaction (PCR) throughout the 10-day abstinence period for assessing the CBD’s effect (10 and 50 μg/5 μl) on the levels of the mRNA expression of the NSP. The findings suggested that CEM, compared with the control group in the hippocampus, downregulated mRNA expression of NSP. Moreover, a dosage of 50 μg/5μl CBD may possibly enhance the mRNA expression level of BDNF/TrkB and NGF/TrkA in the hippocampus. Besides, the expression raf-1 mRNA level could be reversed significantly by both doses of CBD. According to our results, CBD may partly bring about the neuroprotective effects by modulating the NSP. These findings set forth solid evidence demonstrating that CBD is a protection factor attributed to neuropsychiatric disorders such as METH addiction.

scholarly journals Cannabidiol promotes neurogenesis in the dentate gyrus during an abstinence period in rats following chronic exposure to methamphetamine

2021 ◽  
Author(s):  
Yasaman Razavi ◽  
Fariborz Keyhanfar ◽  
Abbas Haghparast ◽  
Ronak Shabani ◽  
Mehdi Mehdizadeh
Keyword(s):  
Dentate Gyrus ◽  
Chronic Exposure ◽  
Neuronal Degeneration ◽  
Hippocampal Neurogenesis ◽  
Control Group ◽  
Nissl Staining ◽  
Neuroprotective Effects ◽  
Ki 67 ◽  
Promising Therapeutic Approach ◽  
Abstinence Period

Abstract Chronic methamphetamine (meth) abuse can lead to certain deficits in the hippocampal function by affecting the hippocampal neurogenesis and plasticity. To determine whether cannabidiol (CBD) can promote proliferation and maturation of neuronal progenitor cells, this study investigated the CBD effect on neurogenesis in the hippocampal dentate gyrus (DG) following chronic exposure to meth in rats. The rats received 2 mg/kg of meth twice a day for ten days. Next, immunofluorescence was performed to evaluate the effect of intracerebroventricular (ICV) administration of CBD (50 µg/5 µL) over an abstinence period (ten days) on the expression levels of neurogenesis markers, such as Ki67, NeuN, and doublecortin (DCX). Moreover, neuronal degeneration in the hippocampus was assessed using Nissl staining. According to our findings, repeated ICV administration of CBD improved cell proliferation and neurogenesis and increased the number of Ki-67 and DCX-positive cells in the abstinence period. Meanwhile, meth treatment subjects caused a significant decrease in the number of neurogenesis makers, as compared to the control group. The neurogenesis markers (Ki-67 and DCX) could be somewhat reversed, while NeuN did not show any significant increase in the CBD group. Our findings demonstrated that CBD can induce neuroprotective effects by modulating neurogenesis. Therefore, it can provide a promising therapeutic approach to improve cognitive performance following chronic exposure to psychostimulant drugs, including meth.

scholarly journals Short-term effects of triiodothyronine on thyroid hormone receptor alpha by PI3K pathway in adipocytes, 3T3-L1

2014 ◽  
Vol 58 (8) ◽  
pp. 833-837 ◽  
Author(s):  
Miriane de Oliveira ◽  
Regiane Marques Castro Olimpio ◽  
Maria Teresa De Sibio ◽  
Fernanda Cristina Fontes Moretto ◽  
Renata de Azevedo Mello Luvizotto ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Thyroid Hormone Receptor ◽  
Pi3k Pathway ◽  
Control Group ◽  
Pi3k Signaling ◽  
Pi3k Inhibitor Ly294002 ◽  
Receptor Alpha ◽  
Pi3k Signaling Pathway

Objective The present study aimed to examine the effects of thyroid hormone (TH), more precisely triiodothyronine (T3), on the modulation of TH receptor alpha (TRα) mRNA expression and the involvement of the phosphatidyl inositol 3 kinase (PI3K) signaling pathway in adipocytes, 3T3-L1, cell culture. Materials and methods: It was examined the involvement of PI3K pathway in mediating T3 effects by treating 3T3-L1 adipocytes with physiological (P=10nM) or supraphysiological (SI =100 nM) T3 doses during one hour (short time), in the absence or the presence of PI3K inhibitor (LY294002). The absence of any treatment was considered the control group (C). RT-qPCR was used for mRNA expression analyzes. For data analyzes ANOVA complemented with Tukey’s test was used at 5% significance level. Results T3 increased TRα mRNA expression in P (1.91±0.13, p<0.001), SI (2.14±0.44, p<0.001) compared to C group (1±0.08). This increase was completely abrogated by LY294002 in P (0.53±0.03, p<0.001) and SI (0.31±0.03, p<0.001). To examine whether TRα is directly induced by T3, we used the translation inhibitor cycloheximide (CHX). The presence of CHX completely abrogated levels TRα mRNA in P (1.15±0.05, p>0.001) and SI (0.99±0.15, p>0.001), induced by T3. Conclusion These results demonstrate that the activation of the PI3K signaling pathway has a role in T3-mediated indirect TRα gene expression in 3T3-L1 adipocytes.

scholarly journals Protective effects of ginkgolide on a cellular model of Alzheimer’s disease via suppression of the NF-κB signaling pathway

2021 ◽  
Author(s):  
Tiantong Niu ◽  
He Yin ◽  
Baolei Xu ◽  
Tingting Yang ◽  
Huiqin Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Viability ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Hek293 Cells ◽  
Control Group ◽  
Cellular Model ◽  
Intracellular Protein ◽  
Tnf Α

Abstract NF-κB signaling has been reported to play a key regulatory role in the pathogenesis of Alzheimer’s disease (AD). The purpose of this study is to investigate the effects of ginkgolide on cell viability in an AD cellular model involving an APP/PS1 double gene-transfected HEK293 cell line (APP/PS1-HEK293) and further explored the mechanisms of action related to NF-κB signaling. The optimal time point and concentration of ginkgolide for cell proliferation were screened using a cell counting kit-8 assay. Based on the results, an in vitro study was performed by co-culture of APP/PS1-HEK293 with different dosages of ginkgolide, followed by an enzyme-linked immunosorbent assay to measure the levels of supernatant tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, as well as western blotting and real-time polymerase chain reaction to detect intracellular protein and mRNA expression of NF-κB p65, IκBa, Bcl-2 and Bax. APP/PS1-HEK293 cells exhibited the highest cell viability at a concentration of 100 µg/ml after 48 h of treatment with ginkgolide. The supernatant levels of TNF-α, IL-1β and IL-6 in the high-dosage ginkgolide-treated groups were lower than those in the control group. Compared with the control group, there were decreased intracellular protein and mRNA expression of NF-κB p65 and Bax, but increased protein and mRNA expression of IκBa in both high-dosage and low-dosage group. Ginkgolide may enhance cell viability, indicative of its neuroprotective effects on AD, at least partially via suppression of the NF-κB signaling pathway involving anti-apoptosis and anti-inflammation mechanisms. Therefore, ginkgolide might be a promising therapeutic agent against AD.

Effect of miR-155 on Aplastic Anemia Rats Through Regulating Signal Transducer and Activator of Transcription 3 Signaling Pathway

2020 ◽  
Vol 10 (3) ◽  
pp. 397-401
Author(s):  
Qingxian Yan ◽  
Zhengjun Hou ◽  
Shuting Ye ◽  
Meiyun Su
Keyword(s):  
Aplastic Anemia ◽  
Signaling Pathway ◽  
Blood Cells ◽  
Mrna Level ◽  
White Blood Cells ◽  
Control Group ◽  
Stat3 Signaling ◽  
Group I ◽  
Stat3 Signaling Pathway ◽  
Experimental Group

Objective: To assess miR-155’s effect on aplastic anemia (AA) rats. Methods: In the present study, the healthy rats (control group) and AA rats including AA rats with miR-155 overexpression (experimental group I) and those with miR-155 deficiency (experimental group II), were selected. The levels of miR-155, STAT3 (a key gene in STAT3 signaling pathway) and phosphorylated STAT3 (p-STAT3) in control group and experimental group were detected via qPCR and Western blotting. Moreover, the number of white blood cells (WBCs), red blood cells (RBCs), platelets (PLTs) and hemoglobin (HGB) level were also measured. Results: The level of miR-155 in AA rats was significantly declined compared with that in healthy rats (p < 0.05). STAT3 mRNA level was significantly declined in AA rats with miR-155 overexpression compared with that in AA rats with miR-155 deficiency (p < 0.05). STAT3 and p-STAT3 protein expression in AA rats with miR-155 overexpression were significantly lower than those in AA rats with miR-155 deficiency (p < 0.05). Besides, it was found that the number of WBC, RBC, PLT and HGB level were significantly elevated in AA rats with miR-155 overexpression compared to those in AA rats with miR-155 deficiency (p < 0.05). Conclusion: miR-155 can improve the AA symptoms of rats through inhibiting the STAT3 signaling pathway.

scholarly journals mRNA Expression of CYP2E1, CYP2A19, CYP1A2, HSD3B, SULT1A1 and SULT2A1 genes in surgically castrated, immunologically castrated, entire male and female pigs and correlation with androstenone, skatole, indole and Improvac-specific antibody levels

2019 ◽  
Vol 64 (No. 2) ◽  
pp. 89-97
Author(s):  
A. Kubešová ◽  
K. Šťastný ◽  
M. Faldyna ◽  
Z. Sládek ◽  
I. Steinhauserová ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Mrna Level ◽  
Boar Taint ◽  
Control Group ◽  
Mrna Levels ◽  
Large White ◽  
Specific Antibodies ◽  
Significant Difference ◽  
Entire Male

This study aimed to obtain a comprehensive look at the influence of castration on mRNA expression of the genes CYP2E1, CYP1A2, CYP2A19, HSD3B, SULT2A1 and SULT1A1 and their correlation with boar taint compounds (androstenone, skatole and indole) and Improvac-specific antibodies in a Czech commercial hybrid (Large White × Landrace (sow) × Duroc (boar)). Pigs were divided into groups of entire male pigs (NC), pigs castrated surgically (SC), pigs immunologically castrated and slaughtered 8 weeks (IM8) or 15 weeks (IM15) after the second dose of Improvac, and gilts (GI). Hepatic mRNA expression, measured by quantitative real-time polymerase chain reaction, differed significantly between the control group (entire male pigs) and all groups of interest for CYP2E1, CYP1A2 and CYP2A19. The mRNA level of the HSD3B gene differed significantly between the control group and the IM8, IM15 and GI groups. SULT1A1 gene expression was significantly different between the control group and the SC, IM8 and GI. In the case of SULT2A1, a significant difference was observed only between the control group and IM8 pigs. For all genes and treatment groups described above, expression was increased relative to the control. Significant differences for Improvac-specific antibodies between IM8 and IM15 groups were observed, indicating decrease of antibodies over time. Moreover, negative correlations between androstenone and mRNA levels of CYP2A19, CYP2E1 and SULT1A1 suggest that gene expression is suppressed.

scholarly journals ALTERATION OF CYP3A1 mRNA LEVEL IN PRIMARY RAT HEPATOCYTES IN RESPONSE TO AMPK ACTIVE ATOR AICAR

2019 ◽  
Vol 15 (1) ◽  
pp. e23-29
Author(s):  
Bang-Sub Lee ◽  
Jooyoung Kim ◽  
Wi-Young So
Keyword(s):  
Mrna Expression ◽  
Statistical Significance ◽  
Mrna Level ◽  
Rat Hepatocytes ◽  
Embryoid Bodies ◽  
Primary Hepatocyte ◽  
Control Group ◽  
Energy Status ◽  
Sprague Dawley ◽  
Primary Hepatocytes

Background and Objective AMP-activated protein kinase (AMPK) functions as a sensor of the intracellular energy status that can be stimulated by a synthetic activator, 5-aminoimidazole–4–carboxamide–1–beta–D–ribofuranoside (AICAR), which is used to replicate the effect of physical exercise in hepatocyte embryoid bodies. This study investigated the effect of AICAR on the CYP3A1 mRNA expression in primary hepatocyte embryoid bodies derived from a rat liver. Material and Methods The primary hepatocytes were isolated from a male Sprague Dawley (SD) rat (215 g) and subjected to the following treatments: control without AICAR (CTL, n=3), 1 μM AICAR (n=3), 10 μM AICAR (n=3), and 100 μM AICAR (n=3). RNA was isolated and used as the template for synthesizing cDNA by reverse transcriptase to perform quantitative PCR (qPCR). The independent samples t-test was conducted to examine differences between groups. Statistical significance was set at p<0.05. Results The qPCR analysis demonstrated that CYP3A1 mRNA expression in primary hepatocyte embryoid bodies significantly increased in the presence of 10 μM (t=1.730, p<0.05) and 100 μM AICAR (t=3.207, p<0.05) as compared to that in the control group hepatocytes. However, the observed increase of CYP3A1 mRNA in hepatocyte embryoid bodies was not statistically significant in the presence of 1 μM AICAR as the lowest test concentration. Conclusion In this study, we demonstrated that AICAR, an AMPK activator, can increase the expression of CYP3A1 mRNA in primary hepatocytes. Future studies should assess the effect of AICAR treatment on CYP3A4 in human hepatocytes.

scholarly journals A Multimodal MR Imaging Study of the Effect of Hippocampal Damage on Affective and Cognitive Functions in a Rat Model of Chronic Exposure to a Plateau Environment

2022 ◽  
Author(s):  
Dongyong Zhu ◽  
Bo He ◽  
Mengdi Zhang ◽  
Yixuan Wan ◽  
Ruibin Liu ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Rat Model ◽  
Chronic Exposure ◽  
Imaging Techniques ◽  
Male Rats ◽  
Chemical Exchange Saturation Transfer ◽  
Tibet Plateau ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Hippocampal Damage

AbstractProlonged exposure to high altitudes above 2500 m above sea level (a.s.l.) can cause cognitive and behavioral dysfunctions. Herein, we sought to investigate the effects of chronic exposure to plateau hypoxia on the hippocampus in a rat model by using voxel-based morphometry, creatine chemical exchange saturation transfer (CrCEST) and dynamic contrast-enhanced MR imaging techniques. 58 healthy 4-week-old male rats were randomized into plateau hypoxia rats (H group) as the experimental group and plain rats (P group) as the control group. H group rats were transported from Chengdu (500 m a.s.l.), a city in a plateau located in southwestern China, to the Qinghai–Tibet Plateau (4250 m a.s.l.), Yushu, China, and then fed for 8 months there, while P group rats were fed in Chengdu (500 m a.s.l.), China. After 8 months of exposure to plateau hypoxia, open-field and elevated plus maze tests revealed that the anxiety-like behavior of the H group rats was more serious than that of the P group rats, and the Morris water maze test revealed impaired spatial memory function in the H group rats. Multimodal MR imaging analysis revealed a decreased volume of the regional gray matter, lower CrCEST contrast and higher transport coefficient Ktrans in the hippocampus compared with the P group rats. Further correlation analysis found associations of quantitative MRI parameters of the hippocampus with the behavioral performance of H group rats. In this study, we validated the viability of using noninvasive multimodal MR imaging techniques to evaluate the effects of chronic exposure to a plateau hypoxic environment on the hippocampus.

Changes of Metallothionein 1 and 3 mRNA Levels with Age in Brain of Senescence-Accelerated Mice and The Effects of Acupuncture

2006 ◽  
Vol 34 (03) ◽  
pp. 435-447 ◽  
Author(s):  
Tingyi Wen ◽  
Xiaonong Fan ◽  
Mingchun Li ◽  
Jingxian Han ◽  
Xuemin Shi ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Mrna Level ◽  
Zinc Ion ◽  
Control Group ◽  
Mrna Levels ◽  
Expression Levels ◽  
Age Related ◽  
Zigzag Pattern ◽  
Effects Of Aging ◽  
Senescence Accelerated Mice

The effects of aging and acupuncture on brain MT1 and MT3 mRNA levels in senescence-accelerated mice (SAMP10) and accelerated senescence resistant mice (SAMR1) were analyzed by Northern blot analysis. Both MT1 and MT3 mRNA levels in SAMR1 were increased significantly from birth to month 4 and decreased gradually thereafter. In SAMP10, the MT3 mRNA level followed the same pattern as in SAMR1 before month 4, then decreased from month 4 to 6, but was over-expressed and exceeded the previous level at month 8. The MT1 mRNA expression in SAMP10 showed a zigzag pattern. Of two groups of SAMP10 mice treated with acupuncture, the Xingnao group (PC6 and Du26 as acupoints) and the Zibuganshen group (BL18 and BL23 as acupoints), both showed a higher MT1 mRNA level and a lower MT3 mRNA level than the age-matched control group. Meanwhile, in both of the acupuncture groups, the ratios of MT3 to MT1 were down-regulated to the normal range. Overall, these results suggested that over-expression of MT3 mRNA and the increase in MT3 to MT1 ratios in SAMP10 were correlated with aging, and could be an important physiological and pathological event in the aging process. Acupuncture altered the expression levels of MT1 and MT3 mRNA and differences between the effects of the two stimulated acupoints were seen. Therefore, maintenance of the balance between MTs mRNA expression and correct MTs concentrations is crucial for brain-endocrine-immune response and normal aging. Acupuncture could improve zinc ion bioavailability, by maintaining the balance between MT1 and MT3 mRNA expression levels and might explain one of the mechanisms by which acupuncture treatments defer aging and treat some age-related neurodegenerative diseases.

scholarly journals Dendrobium Mixture Improved Diabetic Nephropathy in db/db Mice by Regulating TGF-β1/Smads Signal Transduction

2021 ◽  
Author(s):  
Yong Chen ◽  
Xiaohui Lin ◽  
Yanfang Zheng ◽  
Wenzhen Yu ◽  
Fan Lin ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Diabetic Nephropathy ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Fasting Blood Glucose ◽  
Blood Lipid ◽  
Control Group ◽  
Tgf Β1

Abstract BackgroundDendrobium mixture (DMix) is an effective treatment for diabetic nephropathy (DN), but the underlying molecular mechanism remains unclear. In this study, we investigated whether DMix regulates the transforming growth factor-β1 (TGF-β1)/Smads signal transduction pathway. MethodsTwenty-four db/db mice were randomly divided into three groups: the model, DMix, and gliquidone groups, while eight db/m mice were selected as the normal control group. The drug was administered by continuous gavage for 8 weeks. Body weight (BW), kidney weight (KW), kidney index, fasting blood glucose (FBG), blood lipid, 24-hour urinary albumin excretion rate, blood urea nitrogen, and serum creatinine levels were measured. Pathological changes in the renal tissue were observed using a light microscope. Real-time quantitative PCR and immunohistochemical staining were used to detect mRNA expression of TGF-β1 and alpha-smooth muscle actin (α-SMA) genes and proteins, respectively, in renal tissues. TGF-β1, Smad2, p-Smad2, Smad3, p-Smad3, and α-SMA expression levels were measured using western blotting. ResultsDMix significantly reduced FBG level, BW, KW, and blood lipid level, and improved renal function in db/db mice. Histopathology showed that DMix alleviated glomerular mesangial cell proliferation and renal interstitial fibrosis in db/db mice. Additionally, DMix reduced protein and mRNA expression of TGF-β1 and α-SMA, and inhibited Smad2 and Smad3 phosphorylation. ConclusionsThe findings suggest that DMix may inhibit renal fibrosis and delay the progression of DN by regulating the TGF-β1/Smads signaling pathway. Key words: Diabetic nephropathy, Dendrobium mixture, TGF-β1/Smads signaling pathway

scholarly journals The p53 signaling pathway of the large yellow croaker (Larimichthys crocea) responds to acute cold stress: evidence via spatiotemporal expression analysis of p53, p21, MDM2, IGF-1, Gadd45, Fas, and Akt

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10532
Author(s):  
Baoying Qian ◽  
Xin Qi ◽  
Yi Bai ◽  
Yubo Wu
Keyword(s):  
Cold Stress ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Environmental Stressors ◽  
Control Group ◽  
Large Yellow Croaker ◽  
Larimichthys Crocea ◽  
Expression Levels ◽  
P53 Signaling ◽  
Cycle Arrest

The p53 activation is induced by stressors, such as DNA damage, oxidative stress, and activated oncogenes, and can promote cell cycle arrest, cellular senescence, and apoptosis. The large yellow croaker (Larimichthys crocea) is an important warm temperate marine fish in the Chinese aquiculture industry. However, few studies have investigated the role of p53 in the response of L. crocea to environmental stressors. Therefore, the aim of the present study was to assess the spatiotemporal mRNA expression levels of genes involved in the p53 signaling pathway of the large yellow croaker in response to cold stress. The results showed significant changes in the expression levels of p53, p21, MDM2, IGF-1, Gadd45, Fas, and Akt in various tissues of the large yellow croaker in response to cold stress for different times. As compared to the control group, p53 mRNA expression was upregulated in most of the examined tissues at 24 h with the exception of the gill. In the liver, the expression levels of p53 and Fas were significantly decreased at 12 h, while those of p21, MDM2, IGF-1, Gadd45 were dramatically increased. Akt expression was notably changed in response to cold in several tissues. These results suggested that p53 was potentially a key gene in the large yellow croaker response to cold and possibly other environmental stressors.

Sign in / Sign up

Export Citation Format

Share Document