Neuroprotective effects of thymoquinone against MDMA-induced neurotoxicity

Author(s):  
Mustafa NS. ◽  
Mohamad N. ◽  
Abu Bakar NH. ◽  
Mohd Adnan LH. ◽  
Jeharsae R. ◽  
...  

MDMA (3, 4-methylenedioxymethamphetamine) is a psychoactive substance that is associated with neurotoxicity. MDMA exposure to human results in the degeneration of neuronal cells in the hippocampus. Hence, the purpose of this study was to examine the potential of a natural compound known as thymoquinone (TQ) to protect against neuronal damage and memory impairment in rats stimulated by MDMA. The administration of TQ into MDMA-induced neuronal damage rats was carried out in male Sprague Dawley via a 1-week treatment dividing into four groups (n=36, 7-9 per group). The studied groups involved with the treatments comprise i) Control (1 mL/kg saline), ii) MDMA (10 mg/kg MDMA), iii) MDMA+TQ (10 mg/kg MDMA + 40 mg/kg TQ) and iv) TQ control (40 mg/kg TQ). A novel object recognition test (NORT) was carried out to evaluate the memory performance of the rats, followed by a histopathological assessment of the hippocampal dentate gyrus. The histopathology analysis revealed a significant increase in numbers of positive cells by Fluoro-Jade C following the effect of MDMA on neuronal damage (MDMA induced group) compared to control (P<0.05). Next, the TQ treatments observed in MDMA+TQ exhibited a decline in positive cells from Fluoro-Jade C. The index of recognition memory was found to be increased in MDMA+TQ compared to the MDMA alone (P<0.05). This study suggests that the neuronal damage inflicted by MDMA in a rat model has the potential to be treated by TQ.

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Olusegun G. Adebayo ◽  
Samuel A. Onasanwo ◽  
Abayomi M. Ajayi ◽  
Wadioni Aduema ◽  
Oyetola T. Oyebanjo ◽  
...  

Abstract Objectives Cnidoscolus aconitifolius have been investigated to have abundant phytochemicals. However, study on the effect of Cnidoscolus aconitifolius on neurobehavioral performance when supplemented with diet is lacking. The study is aimed at investigating the memory-enhancing effect of Cnidoscolus aconitifolius-supplemented diet (CAD) using Morris water maze and Novel object recognition test. Methods Ninety male Wistar rats (80–100 g) were fed with CAD (1, 2.5, 5 and 10%) continuously for a period of 4, 8 and 12 weeks respectively. Six animals per group were used for assessment of memory performance (Morris water maze [MWM] and Novel object recognition test [NORT]); afterwards the brain tissues were harvested for malondialdehyde (MDA), glutathione (GSH) and catalase (CAT) estimation. Acetylcholinesterase (AChE) concentration was also determined. Hippocampal architectural change in the neuron was examined using hematoxylin and eosin (H&E) and cresyl fast violet (Nissl) stain. Results Higher percentage of CAD significantly (p<0.05) improve memory performance with time-dependent effects in rats fed with CAD on MMW and NORT. MDA significantly (p<0.05) reduce in 1 and 2.5% CAD groups at 4th weeks and in 2.5 and 5% CAD groups at 8th weeks while GSH concentration significantly (p<0.05) increase at 12th weeks in 2.5 and 10% CAD groups. However, CAT concentration significantly (p<0.05) increase in 2.5, and 5%, CAD groups, 1, 5, and 10% CAD groups and in 5, and 10% CAD groups at 4th, 8th and 12th weeks. AChE significantly (p<0.05) reduce at 4th and 12th weeks. Histological assessment reveals no neuronal and pyramidal degeneration (chromatolysis) at the hippocampal Cornu Ammonis 3 (CA3) region. Conclusions The results suggest that CAD boost memory performance in rats through positive modulation of oxidative stress, cholinergic system and degeneration of hippocampal neurons.


Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 343 ◽  
Author(s):  
Eunjin Sohn ◽  
Yu Kim ◽  
Hye-Sun Lim ◽  
Bu-Yeo Kim ◽  
Soo-Jin Jeong

Hwangryunhaedok-tang (HRT) is a traditional oriental herbal formula used in Asian countries for treating inflammatory diseases and controlling fever. Our present study aimed to determine whether HRT has therapeutic effects for patients with vascular dementia (VaD) using a bilateral common carotid artery occlusion (BCCAO) rat model and assessing spatial memory impairment and activation of neuroinflammation. BCCAO was performed in male Sprague Dawley rats to induce VaD, and oral HRT was administered daily for 30 d. Our data showed that HRT ameliorated BCCAO-induced memory and cognitive impairment in behavioral tests. In addition, HRT reversed cholinergic dysfunction and neuronal damage in the hippocampus of BCCAO rats. Furthermore, HRT attenuated microglial activation and reduced the phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase (JNK) induced by BCCAO. Simultaneous high-performance liquid chromatography analysis of HRT using index compounds from the herbal composition revealed that both HRT ethanol extract and commercial HRT granules primarily comprise geniposide, baicalin, and berberine. Our study showed that HRT administration resulted in the prevention of neuronal injury induced by BCCAO through improvement of cholinergic dysfunction and inhibition of neuroinflammatory responses, suggesting that HRT may have potential as a treatment for VaD.


2021 ◽  
Vol 14 ◽  
Author(s):  
Lidong Sun ◽  
Donghao Bai ◽  
Maoguang Lin ◽  
Eerdenidalai ◽  
Li Zhang ◽  
...  

Accumulating evidence continues to emphasize the role of microRNAs as significant contributors to depression-like behavior and memory disorders. The current study aimed to investigate the mechanism by which miR-96 influences depression-like behavior and memory deficit in mice. A depression-like behavior and memory disorder mouse model was initially established by means of intraperitoneal injection with lipopolysaccharide. Memory deficits in the mice were evaluated using the Novel Object Recognition Test and Morris water maze experiments, whereas the Sucrose Preference Experiment and forced swimming experiments were performed to identify depression-like behavior in mice. The levels of tumor necrosis factor-α, malondialdehyde, superoxide dismutase, glutathione, and the monoamine transmitters 5-hydroxytryptamine and dopamine were subsequently detected in the serum. Reverse transcription-quantitative polymerase chain reaction and Western blot analysis evaluated the expression of miR-96 and SV2C expression in the CA1 hippocampal region of the mice. Finally, the relationship of miR-96 and SV2C was verified by dual-luciferase reporter gene assay. Our data indicated that the expression of miR-96 was increased, whereas that of SV2C was decreased in the CA1 region of mice exhibiting depression-like behavior and memory impairment. When miR-96 was downregulated or SV2C was overexpressed via intra-cerebroventricular injection with a miR-96 antagonist (miR-96 antagomir) or overexpression of SV2C vector, the Novel Object Recognition Test and sucrose preference index were increased, whereas the escape latency, the number of water maze platform crossings, and the immobility time of the mice were decreased. The serum levels of tumor necrosis factor-α, interleukin-1β, and malondialdehyde in the mouse CA1 region of mice were reduced, whereas the levels of superoxide dismutase and glutathione were elevated after the downregulation of miR-96 or overexpression of SV2C. Collectively, our study demonstrates that miR-96 negatively regulates the expression of SV2C, which consequently leads to depression-like behavior and memory impairment in mice. Our findings highlight the potential of miR-96-targeted therapeutics.


2018 ◽  
Vol 8 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Hamidreza Famitafreshi ◽  
Morteza Karimian

Objective:Social isolation is associated with adverse effects on brain functions. According to previous studies, the reduction of oxidative stress improves cognitive functions. Memory performance is dependent on hippocampus and prefrontal function. The aim of this study is to show that impairment of memory in object recognition test in isolation state is accompanied by deregulation of oxidative stress balance in related areas.Methods and Materials:In this study, 14 male Sprague-Dawley rats were randomly divided into two groups as follows: social and isolation. Socialization and isolation plus one week of acclimatization occurred for fourteen days. At the end of the study, after performing behavioral test, (novel object recognition test) rats were anesthetized and sacrificed. After preparation of tissues in controlled condition, oxidative stress status in hippocampus and prefrontal cortex for Malondialdehyde (MDA), glutathione and nitrite/nitrate was assessed.Results:MDA in the hippocampus and prefrontal cortex was higher in isolated rats compared to social rats. Glutathione and nitrite/nitrate in the hippocampus and prefrontal cortex were lower in isolated rats compared to social rats. Memory performance in novel object recognition test both in short term and long term was better in social rats.Conclusion:Memory performance in novel object recognition test is influenced by social and oxidative stress status. So improving memory is possible through socialization and improvement of antioxidant status.


2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Anil Kumar ◽  
Samrita Dogra ◽  
Atish Prakash

Oxidative stress appears to be an early event involved in the pathogenesis of Alzheimer's disease. The present study was designed to investigate the neuroprotective effects ofCentella asiaticaagainst colchicine-induced memory impairment and oxidative damage in rats. Colchicine (15 μg/5 μL) was administered intracerebroventricularly in the lateral ventricle of male wistar rats. Morris water maze and plus-maze performance tests were used to assess memory performance tasks. Various biochemical parameters such as lipid peroxidation, nitrite, reduced glutathione, glutathione-S-transferase, superoxide dismutase, acetylcholinesterase were also assessed. ICV colchicine resulted marked memory impairment and oxidative damage. Chronic treatment withCentella asiaticaextract (150 and 300 mg/kg, p.o.) for a period of 25 days, beginning 4 days prior to colchicine administration, significantly attenuated colchicine-induced memory impairment and oxidative damage. Besides,Centella asiaticasignificantly reversed colchicines administered increase in acetylcholinesterase activity. Thus, present study indicates protective effect ofCentella asiaticaagainst colchicine-induced cognitive impairment and associated oxidative damage.


2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Juan Ignacio Romero ◽  
Mariana Inés Holubiec ◽  
Tamara Logica Tornatore ◽  
Stéphanie Rivière ◽  
Eva-Maria Hanschmann ◽  
...  

The general disruption of redox signaling following an ischemia-reperfusion episode has been proposed as a crucial component in neuronal death and consequently brain damage. Thioredoxin (Trx) family proteins control redox reactions and ensure protein regulation via specific, oxidative posttranslational modifications as part of cellular signaling processes. Trx proteins function in the manifestation, progression, and recovery following hypoxic/ischemic damage. Here, we analyzed the neuroprotective effects of postinjury, exogenous administration of Grx2 and Trx1 in a neonatal hypoxia/ischemia model. P7 Sprague-Dawley rats were subjected to right common carotid ligation or sham surgery, followed by an exposure to nitrogen. 1 h later, animals were injected i.p. with saline solution, 10 mg/kg recombinant Grx2 or Trx1, and euthanized 72 h postinjury. Results showed that Grx2 administration, and to some extent Trx1, attenuated part of the neuronal damage associated with a perinatal hypoxic/ischemic damage, such as glutamate excitotoxicity, axonal integrity, and astrogliosis. Moreover, these treatments also prevented some of the consequences of the induced neural injury, such as the delay of neurobehavioral development. To our knowledge, this is the first study demonstrating neuroprotective effects of recombinant Trx proteins on the outcome of neonatal hypoxia/ischemia, implying clinical potential as neuroprotective agents that might counteract neonatal hypoxia/ischemia injury.


2011 ◽  
Author(s):  
Matthew Jefferson ◽  
Sara Smeltzer ◽  
Jeffery L. McMillin ◽  
Caitlin C. Henry ◽  
Brittney M. Klauser ◽  
...  

Author(s):  
Saniya Hashim Khan ◽  
Sheraz Khan ◽  
Inamullah Khan ◽  
Narmeen Hashim

Background: Chronic stress elevates the cortisol beyond normal levels, which affects cognition including learning & memory. This injurious effect is primarily mediated via over excitation of metabotropic glucocorticoid receptors (mGR). Methods: The present study was aimed appraise the neuroprotective effects of naturally occurring molecule β-1,3-glucan by interfering with stress-cortisol-mGR axis. Our data of virtual screening (in silico) exhibited the promising interactions of βglucan with the mGR. Therefore, the study was extended to evaluate its efficacy (2.5, 5 and 10 mg/kg/ i.p) in an animal model of chronic unpredictable mild stress (CUMS, 28 days) induced memory impairment. Results: Results of the current study revealed the β-glucan provided dose dependent protection against deleterious effects of stress on learning and memory associated parameters observed in Morris water maze (MWM) task. At higher tested doses, it has also significantly antagonized the stress induced weight loss and corticosterone elevation. Conclusion: From these findings, it can be deduced that the β-glucan possesses therapeutic potential against stress induced memory impairment, and this effect can be attributed to its normalizing effect on corticosterone levels.


Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 768 ◽  
Author(s):  
Corinne Cannavale ◽  
Kelsey Hassevoort ◽  
Caitlyn Edwards ◽  
Sharon Thompson ◽  
Nicholas Burd ◽  
...  

Dietary carotenoids, plant pigments with anti-oxidant properties, accumulate in neural tissue and are often found in lower concentrations among individuals with obesity. Given previous evidence of negative associations between excess adiposity and memory, it is possible that greater carotenoid status may confer neuroprotective effects among persons with overweight or obesity. This study aimed to elucidate relationships between carotenoids assessed in diet, serum, and the macula (macular pigment optical density (MPOD)) and relational memory among adults who are overweight or obese. Adults aged 25–45 years (N = 94) completed a spatial reconstruction task. Task performance was evaluated for accuracy of item placement during reconstruction relative to the location of the item during the study phase. Dietary carotenoids were assessed using 7-day diet records. Serum carotenoids were measured using high-performance liquid chromatography. Hierarchical linear regression analyses were used to determine the relationship between carotenoids and task performance. Although initial correlations indicated that dietary lutein, beta-carotene, and serum beta-carotene were positively associated with memory performance, these relationships were not sustained following adjustment for age, sex, and BMI. Serum lutein remained positively associated with accuracy in object binding and inversely related to misplacement error after controlling for covariates. Macular carotenoids were not related to memory performance. Findings from this study indicate that among the carotenoids evaluated, lutein may play an important role in hippocampal function among adults who are overweight or obese.


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