scholarly journals Subarachnoid hemorrhage leads to early and persistent functional connectivity and behavioral changes in mice

2019 ◽  
Author(s):  
David Y Chung ◽  
Fumiaki Oka ◽  
Gina Jin ◽  
Andrea Harriott ◽  
Sreekanth Kura ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Functional Connectivity ◽  
Open Field ◽  
Morris Water Maze ◽  
Cognitive Deficits ◽  
Water Maze ◽  
Time Points ◽  
Rotarod Performance ◽  
Optical Intrinsic Signal ◽  
Y Maze

AbstractAneurysmal subarachnoid hemorrhage (SAH) leads to significant long-term cognitive deficits. Studies in survivors of SAH show an association between persistent cognitive deficits and alterations in resting state functional connectivity (RSFC). However, modalities commonly used to assess RSFC in humans, such as fMRI, have practical limitations in small animals. Therefore, we used non-invasive functional optical intrinsic signal imaging to determine the effect of SAH on measures of RSFC in mice at early (day 4), intermediate (1 month), and late (3 months) time points after prechiasmatic arterial blood injection. We assessed Morris water maze, open field test, Y-maze, and rotarod performance from approximately 2 weeks to 3 months after SAH induction. We found qualitative and quantitative differences in seed-based connectivity maps between sham and SAH mice. SAH reduced motor, retrosplenial and visual seed-based connectivity indices, which persisted in retrosplenial and visual cortex seeds at 3 months. Seed-to-seed connectivity analysis confirmed attenuation of correlation coefficients in SAH mice, which persisted in predominantly posterior network connections at later time points. Seed-independent global and interhemispheric indices of connectivity revealed decreased correlations following SAH for at least 1 month. SAH led to Morris water maze hidden platform and open field deficits at 2 weeks, and Y-maze deficits for at least 3 months, without altering rotarod performance. In conclusion, experimental SAH leads to early and persistent alterations both in hemodynamically-derived measures of RSFC and in cognitive performance.

scholarly journals Subarachnoid hemorrhage leads to early and persistent functional connectivity and behavioral changes in mice

2020 ◽  
pp. 0271678X2094015
Author(s):  
David Y Chung ◽  
Fumiaki Oka ◽  
Gina Jin ◽  
Andrea Harriott ◽  
Sreekanth Kura ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Functional Connectivity ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Correlation Coefficients ◽  
Resting State Functional Connectivity ◽  
Rotarod Performance ◽  
Intrinsic Signal ◽  
Optical Intrinsic Signal ◽  
Seed Analysis ◽  
Y Maze

Aneurysmal subarachnoid hemorrhage (SAH) leads to significant long-term cognitive deficits, which can be associated with alterations in resting state functional connectivity (RSFC). However, modalities such as fMRI—which is commonly used to assess RSFC in humans—have practical limitations in small animals. Therefore, we used non-invasive optical intrinsic signal imaging to determine the effect of SAH on RSFC in mice up to three months after prechiasmatic blood injection. We assessed Morris water maze (MWM), open field test (OFT), Y-maze, and rotarod performance from approximately two weeks to three months after SAH. Compared to sham, we found that SAH reduced motor, retrosplenial, and visual seed-based connectivity indices. These deficits persisted in retrosplenial and visual cortex seeds at three months. Seed-to-seed analysis confirmed early attenuation of correlation coefficients in SAH mice, which persisted in predominantly posterior network connections at later time points. Seed-independent global and interhemispheric indices of connectivity revealed decreased correlations following SAH for at least one month. SAH led to MWM hidden platform and OFT deficits at two weeks, and Y-maze deficits for at least three months, without altering rotarod performance. In conclusion, experimental SAH leads to early and persistent alterations both in hemodynamically derived measures of RSFC and in cognitive performance.

scholarly journals Amelioration of Scopolamine-Induced Amnesic, Anxiolytic and Antidepressant Effects of Ficus benghalensis in Behavioral Experimental Models

Medicina ◽  
2020 ◽  
Vol 56 (3) ◽  
pp. 144
Author(s):  
Humna Malik ◽  
Sana Javaid ◽  
Muhammad Fawad Rasool ◽  
Noreen Samad ◽  
Syed Rizwan Ahamad ◽  
...  
Keyword(s):  
Passive Avoidance ◽  
Open Field ◽  
Morris Water Maze ◽  
Water Maze ◽  
Elevated Plus Maze ◽  
Methanolic Extract ◽  
Ficus Benghalensis ◽  
Y Maze ◽  
Plus Maze ◽  
Phytochemical Studies

Background and Objectives: Ficus benghalensis (FB) is a commonly found tree in Pakistan and its various parts have folkloric importance in managing neurological ailments. In the present study, methanolic extract of its bark has been tested on an experimental animal model to evaluate memory-enhancing, anxiolytic and antidepressant activities to validate the claimed therapeutic potential. Materials and Methods: Methanolic extract of freshly isolated bark was prepared and subjected to preliminary phytochemical studies and gas chromatography–mass spectrometry (GC–MS) analysis for the presence of phytocomponents. To evaluate its effect on spatial learning, passive-avoidance test–step through (PAT-ST), Y-maze and Morris water maze (MWM) tests were carried out. Open-field (OFT) and elevated plus maze (EPM) tests were employed to explore the anti-anxiety potential of FB while a forced swimming test (FST) was utilized to assess its anti-depressant prospective. FB doses of 100, 200 and 300 mg/kg with positive and negative controls given to Sprague Dawley (SD) rats. Results: phytochemical studies showed the presence of various phytoconstituents including alkaloids, flavonoids, terpenes, phenolics and anthraquinones. The presence of synephrine, aspargine, glucose, fructose and fatty acids was revealed by GC–MS analysis. FB administration led to significant improved memory retention when evaluated through passive avoidance (p < 0.05), Y-maze (p < 0.05) and Morris water maze (p < 0.05) tests in a scopolamine model of amnesic rats. When tested by open field and elevated plus maze tests, FB demonstrated anxiety-resolving characteristics (p < 0.05) as animals dared to stay in open areas more than a control group. Mobility time was increased and immobility time was reduced (p < 0.05–0.01) in rats treated with FB, unveiling the anti-depressant importance of F. benghalensis. Conclusion: methanolic extract of F. benghalensis bark furnished scientific proof behind folkloric claims of the memory improving, anxiety-reducing and depression-resolving characteristics of the plant. These activities might be possible due to interaction of its phytoconstituents with serotonergic, glutamatergic, cholinergic and GABAergic systems in the brain.

Effect of alkaloid extracted from Huperzia phlegmaria on cognitive deficits scopolamine-induced in mice

2020 ◽  
Vol 16 ◽  
Author(s):  
Dang Kim Thu ◽  
Dao Thi Vui ◽  
Nguyen Thi Ngoc Huyen ◽  
Nguyen Thi Thanh Binh ◽  
Nguyen Thi Huyen ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mouse Brain ◽  
Cognitive Deficits ◽  
Inhibitory Activity ◽  
Water Maze ◽  
Ache Activity ◽  
Y Maze ◽  
Ache Inhibitory Activity ◽  
Kinetic Inhibition ◽  
Brain Tissues

Background: Huperzia phlegmaria has been used for the treatment of neurological disorder. Alkaloids are main bioactive compounds found in Huperzia phlegmaria. We aimed to investigate the acetylcholinesterase (AChE) inhibitory activity in vitro of Huperzia phlegmaria alkaloid extract (HpAE) and protective effects on mice which were induced cognitive deficits by scopolamine. Methods: AChE inhibitory activity and kinetic inhibition mechanism was investigated by Ellman's assay. Mice were administrated orally HpAE (30 mg/kg and 60 mg/kg) for fourteen days, and injected scopolamine at a dose of 1 mg/kg intraperitoneally for four days to induce cognitive impairment. The Y-maze and the Morris water maze were used for evaluating the memory behaviors. Acetylcholine (ACh) levels and AChE activity were measured in brain tissue. Glutathione peroxidase (GPx), superoxide dismutase (SOD) activities, and malondialdehyde (MDA) groups were also evaluated in the mouse brain tissues. Results: Our data showed that HpAE had the strong AChE inhibitory activity with an IC50 value of 5.12 ± 0.48 μg/mL in a concentration-dependent manner. Kinetic inhibition analysis demonstrated that HpPAE inhibited AChE followed the mixed inhibition type with Ki (representing the affinity of the enzyme and inhibitor) was 4.37 ± 0.35 µg/mL. Scopolamine induced the cognitive impairment in Morris Water Maze and Y-maze test along with reduced brain levels of ACh and antioxidant enzyme and increased AChE activity in mouse brain tissues. Treatment with HpAE at both dose (30 mg/kg and 60 mg/kg) decreased the SCP-induced cognitive impairment in both behavioral tests along with decreased acetylcholinesterase activity and MDA level, and increased ACh level and antioxidant enzyme in mouse brain tissues. Conclusion: Our results suggested that the HpAE at both dose (30 mg/kg and 60 mg/kg) may be used for prevent and treatment of Alzheimer’s disease.

Protective effect of citicoline against aluminum-induced cognitive impairments in rats

2016 ◽  
Vol 33 (4) ◽  
pp. 308-317 ◽  
Author(s):  
Ahmed O Abdel-Zaher ◽  
Mostafa M Hamdy ◽  
Mahran S Abdel-Rahman ◽  
Doaa H Abd El-hamid
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Passive Avoidance ◽  
Morris Water Maze ◽  
Cognitive Deficits ◽  
Aluminum Chloride ◽  
Water Maze ◽  
Cognitive Impairments ◽  
Radial Arm Maze ◽  
Time Required

The potential protective effect of citicoline on aluminum chloride-induced cognitive deficits was investigated in rats. In a Morris water maze, administration of aluminum chloride to rats for 90 days resulted in increased escape latency to reach the platform and decreased swimming speed in acquisition trials. Similarly, in probe trials, the time required to reach the hidden platform was increased and the time spent in the target quadrant was reduced. Also, administration of aluminum chloride to rats for 90 days increased the reference and working memory errors and time required to end the task in the radial arm maze. In addition, this treatment decreased the step-through latency in the passive avoidance test. Concurrently, treatment of rats with aluminum chloride for 90 days increased hippocampal glutamate, malondialdehyde, and nitrite levels and decreased intracellular reduced glutathione level. In the citicoline-treated group, aluminum chloride-induced learning and memory impairments as assessed by the Morris water maze, radial arm maze, and passive avoidance tests were inhibited. At the same time, treatment of rats with citicoline prevented the biochemical alterations induced by aluminum chloride in the hippocampus. It can be concluded that elevation of hippocampal glutamate level with consequent oxidative stress and nitric oxide (NO) overproduction may play an important role in aluminum-induced cognitive impairments. Also, our results suggest, for the first time, that citicoline can protect against the development of these cognitive deficits through inhibition of aluminum-induced elevation of glutamate level, oxidative stress, and NO overproduction in the hippocampus.

scholarly journals Memory Enhancing Activity of Ethanolic Extract of Delonix regia Leaves against Scopolamine induced Amnesia in Swiss Albino Mice

2021 ◽  
Vol 68 (1) ◽  
Author(s):  
Suwathi Ravichandar ◽  
K.A.S. Mohammed Shafeeq ◽  
S. Karpagam Kumara Sundari ◽  
R. Senthamarai
Keyword(s):  
Morris Water Maze ◽  
Water Maze ◽  
Elevated Plus Maze ◽  
Ethanolic Extract ◽  
Swiss Albino Mice ◽  
Delonix Regia ◽  
Y Maze ◽  
Plus Maze ◽  
Dose Levels ◽  
Memory Enhancing

In traditional system of medicine, various parts of Delonix regia have been used for many ailments. The objective of the present study was to evaluate the memory enhancing activity of Ethanolic Extract of Delonix regia leaves (EEDRL) against scopolamine induced amnesia by using Elevated Plus Maze, Y Maze and Morris Water Maze Models. Ethanolic Extract of Delonix regia was prepared then subjected to phytochemical analysis revealed the presence of flavonoids, alkaloids, carbohydrates, tannins, steroids, terpenoids, phenols and saponins. Acute oral toxicity was performed as per OECD guidelines 423. Based on this, two dose levels of EEDRL were chosen as 200 mg/kg and 400 mg/kg for pharmacological screening. Swiss albino mice were divided into five groups of six animals each. EEDRL at a dose levels 200 mg/kg & 400 mg/kg showed increase in inflexion ratio in Elevated Plus Maze, increase in Percentage alterations in Y Maze & decrease in Escape latency in Morris Water Maze Model compared to disease control in dose dependent manner which indicates that the EEDRL reverses the scopolamine induced amnesia in mice. The memory enhancing activity in mice might be due to facilitation of cholinergic transmission. Hence it can be concluded that Delonix regia appears to be a promising candidate for improving memory, and it would be worthwhile to explore the potential of this plant in the management of Alzheimer patient.

scholarly journals The ApoE-dependent Neuroprotective Effects of Sesamol on Diet-induced Obese Mice: The Role of Gut Microbiota and SCFAs (P06-049-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Tian Yuan ◽  
Zhigang Liu ◽  
Xuebo Liu
Keyword(s):  
Fatty Acids ◽  
Cognitive Deficits ◽  
Water Maze ◽  
Elevated Plus Maze ◽  
Short Chain Fatty Acids ◽  
Microbial Metabolites ◽  
Neuroprotective Effects ◽  
Y Maze ◽  
Plus Maze ◽  
Synapse Ultrastructure

Abstract Objectives Sesamol, an antioxidant lignan from sesame oil, possesses lipid lowering and neuroprotective bioactivities. Considering the distribution of sesamol in gut is much higher than brain after administration, the present work was aimed to elucidate the systemic protective effects of sesamol on dietary-induced cognitive deficits, and to determine the possible link between gut and brain. Methods Both wildtype and ApoE-/- mice were fed with high-fat diet (HFD) and treated with sesamol (0.05%, w/v) in drinking water for 10 weeks. The cognitive and anxiety behavioral assessment were evaluated by Morris-water maze, Y-maze, and elevated plus maze tests. The synapse ultrastructure was also detected by transmission electron microscope. Moreover, the alteration of gut microbiome and microbial metabolites short chain fatty acids (SCFAs) were also determined by 16S rDNA sequencing and GC, respectively. Results Sesamol prevented HFD-induced bodyweight gain, insulin resistance, and hyperlipidemia. However, the behavioral tests including Morris-water maze, Y-maze, and elevated plus maze tests indicated that sesamol could only improve cognitive deficits and anxiety behaviors in wildtype but not ApoE deficient mice. Consistently, sesamol improved synapse ultrastructure and inhibited brain Aβ accumulation in brain in an ApoE-dependent manner. Moreover, sesamol prevented HFD-induced gut barrier damages and systemic inflammation. Sesamol also re-shaped gut microbiome and consequently improved the generation of microbial metabolites short chain fatty acids including acetate, propionate, and butyrate. Conclusions To summarized, this study revealed that the possible mechanism of neuroprotective effects of sesamol might be ApoE-dependent, and the beneficial effects of sesamol on gut microbiota/metabolites could be translated into metabolic and neurodegenerative diseases treatment. Funding Sources This work was financially supported by the National Key Research and Development Program of China, National Natural Science Foundation of China. Supporting Tables, Images and/or Graphs

scholarly journals Chronic Supplementation with a Mix of Salvia officinalis and Salvia lavandulaefolia Improves Morris Water Maze Learning in Normal Adult C57Bl/6J Mice

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1777
Author(s):  
Anne-Laure Dinel ◽  
Céline Lucas ◽  
Damien Guillemet ◽  
Sophie Layé ◽  
Véronique Pallet ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Morris Water Maze ◽  
Neuronal Activity ◽  
Water Maze ◽  
Salvia Officinalis ◽  
Cam Kinase Ii ◽  
Cam Kinase ◽  
Y Maze ◽  
The Impact

Background: Two different species of sage, Salvia officinalis and Salvia lavandulaefolia, have demonstrated activities in cognitive function during preclinical and clinical studies related to impaired health situations or single administration. Different memory processes have been described to be significantly and positively impacted. Objective: Our objective is to explore the potential of these Salvia, and their additional activities, in healthy situations, and during prolonged administration, on memory and subsequent mechanisms of action related to putative effects. Design: This mouse study has implicated four investigational arms dedicated to control, Salvia officinalis aqueous extract, Salvia lavandulaefolia-encapsulated essential oil and a mix thereof (Cognivia™) for 2 weeks of administration. Cognitive functions have been assessed throughout Y-maze and Morris water maze models. The impact of supplementation on lipid peroxidation, oxidative stress, neurogenesis, neuronal activity, neurotrophins, neurotrophin receptors, CaM kinase II and glucocorticoid receptors has been assessed via post-interventional tissue collection. Results: All Salvia groups had a significant effect on Y-maze markers on day 1 of administration. Only the mix of two Salvia species demonstrated significant improvements in Morris water maze markers at the end of administration. Considering all biological and histological markers, we did not observe any significant effect of S. officinalis, S. lavandulaefolia and a mix of Salvia supplementation on lipid peroxidation, oxidative stress and neuronal plasticity (neurogenesis, neuronal activity, neurotrophins). Interestingly, CaM kinase II protein expression is significantly increased in animals supplemented with Salvia. Conclusion: The activities of Salvia alone after one intake have been confirmed; however, a particular combination of different types of Salvia have been shown to improve memory and present specific synergistic effects after chronic administration in healthy mice.

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