Neuroprotective Effect of Celastrus Paniculatus Seed Extract in Epilepsy and Epilepsy-Associated Cognitive Deficits

Purpose: Cognitive deficit is one of the common comorbidity accompanying epilepsy. The present study evaluated the effect of Celastrus paniculatus (C- paniculatus) seed extract on seizure severity and cognitive deficit following Pentylenetetrazole (PTZ) -induced chemical kindling model. Methods : PTZ kindling model was developed by daily administration of sub-convulsive dose of PTZ 30 mg/kg for 4 weeks. After 4 weeks of induction, the following treatment namely Sodium valproic acid (SVA) 200 mg/kg, C- paniculatus 500 mgkg, Pergolide 2 mg/kg alone and combination groups C- paniculatus 250 mgkg+ Pergolide 1 mg/kg and C- paniculatus 250 mgkg+ SVA 100 mg/kg were administered 30 minute prior to PTZ 30 mg/kg injection for a period of next 14 days. Neurobehavioral parameters Morris water maze test (MWM), Grip strength test (GPS) brain superoxide dismutase (SOD), Catalase, reduced glutathione (GSH) and dopamine level. Hematoxylin & Eosin (H&E) staining of hippocampus pyramidal layers Cornu ammonis (CA1), CA2, CA3, dentate gyrus (DG), and frontal cortex were assessed. Results: C- paniculatus 500 mg/kg alone and combination groups C- paniculatus 250 mgkg+ Pergolide 1 mg/kg and Celastrus paniculatus 250 mgkg+ SVA 100 mg/kg significantly (p<0.05) reduced the seizure score, mean latency time, and distance traveled in MWM. However, no significant effect was seen in grip strength test. Biochemical analysis showed elevated antioxidant markers namely GSH, catalase, and SOD & elevated dopamine levels. C- paniculatus and its combination were also found significantly (p<0.05) protected against neuronal loss in hippocampus and frontal cortex as evidenced by H&E staining. Conclusion: C- paniculatus alone and its combination may have the potential to treat epilepsy and associated cognitive deficits.

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Resveratrol Rescues Tau-Induced Cognitive Deficits and Neuropathology in a Mouse Model of Tauopathy

Current Alzheimer Research ◽

10.2174/1567205016666190801153751 ◽

2019 ◽

Vol 16 (8) ◽

pp. 710-722 ◽

Cited By ~ 11

Author(s):

Xiao-Ying Sun ◽

Quan-Xiu Dong ◽

Jie Zhu ◽

Xun Sun ◽

Li-Fan Zhang ◽

...

Keyword(s):

Cognitive Deficits ◽

Therapeutic Potential ◽

Amyloid Β ◽

Synaptic Proteins ◽

Morris Water Maze Test ◽

Phosphorylated Tau ◽

Tau Pathology ◽

Maze Test ◽

N2a Cells ◽

Tau Aggregation

Background: Alzheimer’s Disease (AD) is characterized by the presence of extracellular amyloid-β (Aβ) plaques and intraneuronal neurofibrillary tangles assembled by the microtubuleassociated protein tau. Increasing evidence demonstrated that tau pathology played an important role in AD progression. Resveratrol (RSV) has previously proved to exert neuroprotective effect against AD by inhibiting Aβ generation and Aβ-induced neurocytotoxicity, while its effect on tau pathology is still unknown. Method: The effect of RSV on tau aggregation was measured by Thioflavin T fluorescence and Transmission electron microscope imaging. The effect of RSV on tau oligomer-induced cytotoxicity was assessed by MTT assay and the uptake of extracellular tau by N2a cells was determined by immunocytochemistry. 6-month-old male PS19 mice were treated with RSV or vehicle by oral administration (gavage) once a day for 5 weeks. The cognitive performance was determined using Morris water maze test, object recognition test and Y-maze test. The levels of phosphorylated-tau, gliosis, proinflammatory cytokines such as TNF-α and IL-1β, and synaptic proteins including synaptophysin and PSD95 in the brains of the mice were evaluated by immunoblotting, immunostaining and ELISA, respectively. Results: RSV significantly inhibited tau aggregation and tau oligomer-induced cytotoxicity, and blocked the uptake of extracellular tau oligomers by N2a cells. When applied to PS19 mice, RSV treatment effectively rescued cognitive deficits, reducing the levels of phosphorylated tau, neuroinflammation and synapse loss in the brains of mice. Conclusion: These findings suggest that RSV has promising therapeutic potential for AD and other tauopathies.

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Impaired cholinergic mechanisms following exposure to monocrotophos in young rats

Human & Experimental Toxicology ◽

10.1177/0960327111405860 ◽

2011 ◽

Vol 31 (6) ◽

pp. 606-616 ◽

Cited By ~ 6

Author(s):

Madhu Lata Sankhwar ◽

Rajesh S Yadav ◽

Rajendra K Shukla ◽

Aditya B Pant ◽

Dhirendra Singh ◽

...

Keyword(s):

Body Weight ◽

Frontal Cortex ◽

Grip Strength ◽

Repeated Exposure ◽

Learning Ability ◽

Cholinergic Mechanisms ◽

Young Rats ◽

High Consumption ◽

Quinuclidinyl Benzilate

Studies on the neurobehavioral toxicity of monocrotophos, an organophosphate, have been carried out on rats following their exposure from postnatal day (PD) 22 to PD 49 to investigate whether neurobehavioral changes are transient or persistent. Exposure of rats to monocrotophos (0.50 or 1.0 mg/kg body weight, p.o.) decreased body weight (10% and 30%) and impaired grip strength (28% and 32%) and learning ability (65% and 68%) at both the doses, respectively in comparison to controls. A trend of recovery was observed in body weight and learning, while decrease in grip strength persisted in rats 15 days after withdrawal. Activity of acetylcholinesterase was decreased in frontal cortex (36% and 67%), hippocampus (21% and 49%) and cerebellum (29% and 51%) in monocrotophos-treated rats at both the doses. The decrease in the activity of acetylcholinesterase persisted in frontal cortex and hippocampus; however, a trend of recovery was observed in cerebellum 15 days after withdrawal. Binding of 3 H-quinuclidinyl benzilate ( 3 H-QNB) to frontocortical (19% and 35%), hippocampal (32% and 39%) and cerebellar (19% and 28%) membranes was decreased in monocrotophos-treated rats compared to controls. The decrease in the binding of 3 H-QNB persisted in frontocortical, hippocampal and cerebellar membranes 15 days after withdrawal. The results suggest that repeated exposure to monocrotophos in rats may cause behavioral and neurochemical modifications which may persist even after withdrawal. The findings are of concern in view of the high consumption of monocrotophos in many countries.

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Evaluation of acetylcholinesterase activity and behavioural alterations induced by ketamine in an animal model of schizophrenia

Acta Neuropsychiatrica ◽

10.1017/neu.2013.31 ◽

2013 ◽

Vol 26 (1) ◽

pp. 43-50 ◽

Cited By ~ 9

Author(s):

Alexandra I. Zugno ◽

Maria Paula Matos ◽

Leila Canever ◽

Daiane B. Fraga ◽

Renata D. De Luca ◽

...

Keyword(s):

Animal Model ◽

Cognitive Deficits ◽

Cholinergic System ◽

Ache Activity ◽

Cognitive Deficit ◽

Chronic Administration ◽

Inhibitory Avoidance ◽

Acetylcholinesterase Activity ◽

Chronic Effects ◽

Behavioural Tests

ObjectiveCognitive deficits in schizophrenia play a crucial role in its clinical manifestation and seem to be related to changes in the cholinergic system, specifically the action of acetylcholinesterase (AChE). Considering this context, the aim of this study was to evaluate the chronic effects of ketamine in the activity of AChE, as well as in behavioural parameters involving learning and memory.MethodsThe ketamine was administered for 7 days. A duration of 24 h after the last injection, the animals were submitted to behavioural tests. The activity of AChE in prefrontal cortex, hippocampus and striatum was measured at different times after the last injection (1, 3, 6 and 24 h).ResultsThe results indicate that ketamine did not affect locomotor activity and stereotypical movements. However, a cognitive deficit was observed in these animals by examining their behaviour in inhibitory avoidance. In addition, an increase in AChE activity was observed in all structures analysed 1, 3 and 6 h after the last injection. Differently, serum activity of AChE was similar between groups.ConclusionChronic administration of ketamine in an animal model of schizophrenia generates increased AChE levels in different brain tissues of rats that lead to cognitive deficits. Therefore, further studies are needed to elucidate the complex mechanisms associated with schizophrenia.

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Flos Puerariae Extract Ameliorates Cognitive Impairment in Streptozotocin-Induced Diabetic Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/873243 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Zhong-he Liu ◽

Hong-guang Chen ◽

Pan-feng Wu ◽

Qing Yao ◽

Hong-ke Cheng ◽

...

Keyword(s):

Body Weight ◽

Cerebral Cortex ◽

Cognitive Impairment ◽

Cognitive Deficits ◽

Ache Activity ◽

Memory Deficits ◽

Test Body ◽

Morris Water Maze Test ◽

Diabetic Mice ◽

Mice Model

Objective. The effects of Flos Puerariae extract (FPE) on cognitive impairment associated with diabetes were assessed in C57BL/6J mice.Methods. Experimental diabetic mice model was induced by one injection of 50 mg/kg streptozotocin (STZ) for 5 days consecutively. FPE was orally administrated at the dosages of 50, 100, or 200 mg/kg/day, respectively. The learning and memory ability was assessed by Morris water maze test. Body weight, blood glucose, free fatty acid (FFA) and total cholesterol (TCH) in serum, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and acetylcholinesterase (AChE) activities in cerebral cortex and hippocampus were also measured.Results. Oral administration of FPE significantly improved cognitive deficits in STZ-induced diabetic mice. FPE treatment also maintained body weight and ameliorated hyperglycemia and dyslipidemia in diabetic mice. Additionally, decreased MDA level, enhanced CAT, and GSH-Px activities in cerebral cortex or hippocampus, as well as alleviated AChE activity in cerebral cortex, were found in diabetic mice supplemented with FPE.Conclusion. This study suggests that FPE ameliorates memory deficits in experimental diabetic mice, at least partly through the normalization of metabolic abnormalities, ameliorated oxidative stress, and AChE activity in brain.

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Deficits in motor and cognitive functions in an adult mouse model of hypoxia-ischemia induced stroke

Scientific Reports ◽

10.1038/s41598-020-77678-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Li Feng ◽

Chun-Xia Han ◽

Shu-Yu Cao ◽

He-Ming Zhang ◽

Gang-Yi Wu

Keyword(s):

Cognitive Deficits ◽

Neuronal Loss ◽

Behavioral Changes ◽

Morris Water Maze Test ◽

Functional Deficits ◽

Stroke Research ◽

Ipsilateral Striatum ◽

Histological Data ◽

The Right

AbstractIschemic strokes cause devastating brain damage and functional deficits with few treatments available. Previous studies have shown that the ischemia-hypoxia rapidly induces clinically similar thrombosis and neuronal loss, but any resulting behavioral changes are largely unknown. The goal of this study was to evaluate motor and cognitive deficits in adult HI mice. Following a previously established procedure, HI mouse models were induced by first ligating the right common carotid artery and followed by hypoxia. Histological data showed significant long-term neuronal losses and reactive glial cells in the ipsilateral striatum and hippocampus of the HI mice. Whereas the open field test and the rotarod test could not reliably distinguish between the sham and HI mice, in the tapered beam and wire-hanging tests, the HI mice showed short-term and long-term deficits, as evidenced by the increased number of foot faults and decreased hanging time respectively. In cognitive tests, the HI mice swam longer distances and needed more time to find the platform in the Morris water maze test and showed shorter freezing time in fear contextual tests after fear training. In conclusion, this study demonstrates that adult HI mice have motor and cognitive deficits and could be useful models for preclinical stroke research.

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Characterization of acute adverse-effect profiles of selected antiepileptic drugs in the grip-strength test in mice

Pharmacological Reports ◽

10.1016/s1734-1140(09)70128-8 ◽

2009 ◽

Vol 61 (4) ◽

pp. 737-742 ◽

Cited By ~ 16

Author(s):

Anna Zadrożniak ◽

Ewa Wojda ◽

Aleksandra Wlaź ◽

Jarogniew J. Łuszczki

Keyword(s):

Adverse Effect ◽

Grip Strength ◽

Antiepileptic Drugs ◽

Strength Test ◽

Acute Adverse Effect

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Jia-Wei-Kai-Xin-San, an Herbal Medicine Formula, Ameliorates Cognitive Deficits via Modulating Metabolism of Beta Amyloid Protein and Neurotrophic Factors in Hippocampus of Aβ1-42 Induced Cognitive Deficit Mice

Frontiers in Pharmacology ◽

10.3389/fphar.2019.00258 ◽

2019 ◽

Vol 10 ◽

Author(s):

Yue Zhu ◽

Yiwei Shi ◽

Cheng Cao ◽

Zhenxiang Han ◽

Mengqiu Liu ◽

...

Keyword(s):

Herbal Medicine ◽

Cognitive Deficits ◽

Neurotrophic Factors ◽

Cognitive Deficit ◽

Beta Amyloid ◽

Amyloid Protein ◽

Beta Amyloid Protein

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Protective Effects of Centella asiatica on Cognitive Deficits Induced by D-gal/AlCl3 via Inhibition of Oxidative Stress and Attenuation of Acetylcholinesterase Level

Toxics ◽

10.3390/toxics7020019 ◽

2019 ◽

Vol 7 (2) ◽

pp. 19 ◽

Cited By ~ 7

Author(s):

Samaila Chiroma ◽

Mohamad Baharuldin ◽

Che Mat Taib ◽

Zulkhairi Amom ◽

Saravanan Jagadeesan ◽

...

Keyword(s):

Oxidative Stress ◽

Cerebral Cortex ◽

Prefrontal Cortex ◽

Cognitive Deficits ◽

Neurodegenerative Disorder ◽

Centella Asiatica ◽

Morris Water Maze Test ◽

Enzyme Linked Immunosorbent Assay ◽

Protective Effects ◽

Ultrastructural Alteration

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cholinergic dysfunctions and impaired redox homeostasis. The plant Centella asiatica (CA) is renowned for its nutritional benefits and herbal formulas for promoting health, enhancing cognition, and its neuroprotective effects. The present study aims to investigate the protective role of CA on D-gal/AlCl3-induced cognitive deficits in rats. The rats were divided into six groups and administered with donepezil 1 mg/kg/day, CA (200, 400, and 800 mg/kg/day) and D-gal 60 mg/kg/day + AlCl3 200 mg/kg/day for 10 weeks. The ethology of the rats was evaluated by the Morris water maze test. The levels of acetylcholinesterase (AChE), phosphorylated tau (P-tau), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), in the hippocampus and cerebral cortex were estimated by enzyme-linked immunosorbent assay (ELISA). Additionally, the ultrastructure of the prefrontal cortex of the rats’ was observed using transmission electron microscopy (TEM). Rats administered with D-gal/AlCl3 exhibited cognitive deficits, decreased activities of SOD, and marked increase in AChE and MDA levels. Further, prominent alterations in the ultrastructure of the prefrontal cortex were observed. Conversely, co-administration of CA with D-gal/AlCl3 improved cognitive impairment, decreased AChE levels, attenuated the oxidative stress in hippocampus and cerebral cortex, and prevented ultrastructural alteration of neurons in the prefrontal cortex. Irrespective of the dose of CA administered, the protective effects were comparable to donepezil. In conclusion, this study suggests that CA attenuated the cognitive deficits in rats by restoring cholinergic function, attenuating oxidative stress, and preventing the morphological aberrations.

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S-Adenosylmethionine Rescues Cognitive Deficits in the rTg4510 Animal Model by Stabilizing Protein Phosphatase 2A and Reducing Phosphorylated Tau

Journal of Alzheimer s Disease ◽

10.3233/jad-200756 ◽

2020 ◽

Vol 77 (4) ◽

pp. 1705-1715

Author(s):

Leah C. Beauchamp ◽

Xiang M. Liu ◽

Amelia Sedjahtera ◽

Mirjana Bogeski ◽

Laura J. Vella ◽

...

Keyword(s):

Cognitive Deficits ◽

Protein Phosphatase ◽

Cognitive Deficit ◽

Protein Phosphatase 2A ◽

Phosphorylated Tau ◽

Oral Gavage ◽

Neuronal Homeostasis ◽

Y Maze ◽

Phosphatase 2A ◽

Spatial Recognition

Background: Alterations in the methionine cycle and abnormal tau phosphorylation are implicated in many neurodegenerative diseases, including Alzheimer’s disease and frontotemporal dementia. rTg4510 mice express mutant human P301L tau and are a model of tau hyperphosphorylation. The cognitive deficit seen in these animals correlates with a burden of hyperphosphorylated tau and is a model to test therapies aimed at lowering phosphorylated tau. Objective: This study aimed to increase protein phosphatase 2A activity through supplementation of S-adenosylmethionine and analyze the effect on spatial memory and tau in treated animals. Methods: 6-month-old rTg4510 mice were treated with 100 mg/kg S-adenosylmethionine by oral gavage for 3 weeks. Spatial recognition memory was tested in the Y-maze. Alterations to phosphorylated tau and protein phosphatase 2A were explored using immunohistochemistry, western blot, and enzyme-linked immunosorbent assays. Results: Treatment with S-adenosylmethionine increased the Y-maze novel arm exploration time and increased both the expression and activity of protein phosphatase 2A. Furthermore, treatment reduced the number of AT8 positive neurons and reduced the expression of phosphorylated tau (Ser202/Thr205). S-adenosylmethionine contributes to multiple pathways in neuronal homeostasis and neurodegeneration. Conclusion: This study shows that supplementation with S-adenosylmethionine stabilizes the heterotrimeric form of PP2A resulting in an increase the enzymatic activity, a reduced level of pathological tau, and improved cognition.

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