Memory Impairment In Rat Model Research Articles

Antioxidant, antidiabetic, and anticholinesterase potential of Chenopodium murale L. extracts using in vitro and in vivo approaches

Abstract In this study, Chenopodium murale Linn. extracts have been evaluated for its in vitro antioxidant, enzyme inhibition, and in vivo neuropharmacological properties in streptozotocin (STZ)-induced memory impairment in rat model. First, the plant was subjected to extraction and fractionation, then quantitative phytochemical analysis was performed to estimate the major phytochemical groups in the extract where high amounts of phenolics and saponins were detected in crude and chloroform extract. The highest total phenolic contents, total flavonoid contents, and total tannin content were also recorded in crude extract and chloroform fraction. The in vitro antioxidant potential of chloroform fraction was high with IC50 value of 41.78 and 67.33 μg/mL against DPPH and ABTS radicals, respectively, followed by ethyl acetate fraction. The chloroform fraction (ChMu-Chf) also exhibited potent activity against glucosidase with IC50 of 89.72 ± 0.88 μg/mL followed by ethyl acetate extract (ChMu-Et; IC50 of 140.20 ± 0.98 μg/mL). ChMu-Chf again exhibited potent activity against acetylcholinesterase (AChE) with IC50 of 68.91 ± 0.87 μg/mL followed by ChMu-Et with IC50 of 78.57 ± 0.95 μg/mL. In vivo memory impairment was assessed using the novel object discrimination task, Y-maze, and passive avoidance task. Ex vivo antioxidant enzyme activities and oxidative stress markers like catalase, superoxide dismutase (SOD), malondialdehyde, and glutathione were quantified, and the AChE activity was also determined in the rat brain. No significant differences were observed amongst all the groups treated with crude, chloroform, and ethyl acetate in comparison with positive control donepezil group in connection to initial latency; whereas, the STZ diabetic group displayed a significant fall in recall and retention capability. The blood glucose level was more potently lowered by chloroform extract. The crude extract also increased the SOD level significantly in the brain of the treated rat by 8.01 ± 0.51 and 8.19 ± 0.39 units/mg at 100 and 200 mg/kg body weight (P < 0.01, n = 6), whereas the chloroform extract increased the SOD level to 9.41 ± 0.40 and 9.72 ± 0.51 units/mg, respectively, at 75 and 150 mg/kg body weight as compared to STZ group. The acetylcholine level was also elevated to greater extent by chloroform fraction that might contain a potential inhibitor of acetylcholinesterase. Treatment with C. murale ameliorated cognitive dysfunction in behavioral study, and provided significant defense from neuronal oxidative stress in the brain of the STZ-induced diabetic rats. Thus C. murale Linn. could be an inspiring plant resource that needs to be further investigated for isolation of potential compounds in pure form and their evaluation as a potent neuropharmacological drug.

Autistic Effects of Nootropic Drug Brahmi against Propionic Acid-induced Behavior and Memory Impairment in Rat Model

Aims: To evaluate the hydro alcoholic effect of Brahmi against propionic acid-induced behavior and memory impairment in rat model.
 Study Design: This includes preclinical study on Sprague Dawley rats in which Propionic acid induced and evaluation of in vivo and in vitro models were performed.
 Place and Duration of Study: Department of Pharmacology, C L Baid Metha College of Pharmacy Jan 2019 to June 2021.
 Methodology: We include a total of 27 adult Sprague Dawley Rats and induced propionic acid intracerebroventricular route to induce autism. Drug treatment using hydro alcoholic extract of Bacopa monnieri was given in 250 mg/kg and 500 mg/kg was compared with negative group rats and control groups. In vivo parameters like Actophotometer and marble burying test was done, In vitro analysis of Serotonin and Glutamate was estimated in the above treated groups.
 Results: The locomotor activity of rat was recorded individually for each animal using Actophotometer. HAEBM (250 mg/kg and 500 mg/kg) treated rat produced an increase in the level of significance (P<0.0001) on day one. In marble burying test Rats were located for thirty minutes in a standard cage covered with 5 cm depth of wood chip bedding with ten marbles evenly spaced. HAEBM (250 mg/kg and 500 mg/kg) showed significant (P<0.001) level of burying when compared to group-II rats (P<0.01). In this research study 5HT level showed a significant (P<0.001) increase in Group III, Group IV when compared with group-II (P<0.01). Glutamate is an excitatory Neurotransmitter. Group II showed significant increase (P<0.001) in the level of Glutamate but on drug treated groups III and IV shows decrease in concentration of glutamate.
 Conclusion: The present study findings showed that the hydro alcoholic root extract of brahmi possesses neuroprotective activity with significant nootropic effects. The hydro alcoholic root extract of Bacopa monnieri. L showed the presence of various Gabapentin and flavonoids phenols may be the reason for its neuroprotection and memory improvement effects.

Neuroprotective potency of Tamarindus indica seed extract for preventing memory impairment in rat model of alzheimer's disease

Neuroprotective potency of <i>Tamarindus indica</i> seed extract for preventing memory impairment in rat model of alzheimer's disease

6-Methyluracil derivatives as peripheral site ligand-hydroxamic acid conjugates: Reactivation for paraoxon-inhibited acetylcholinesterase

New uncharged conjugates of 6-methyluracil derivatives with imidazole-2-aldoxime and 1,2,4-triazole-3-hydroxamic acid units were synthesized and studied as reactivators of organophosphate-inhibited cholinesterase. Using paraoxon (POX) as a model organophosphate, it was shown that 6-methyluracil derivatives linked with hydroxamic acid are able to reactivate POX-inhibited human acetylcholinesterase (AChE) in vitro. The reactivating efficacy of one compound (5b) is lower than that of pyridinium-2-aldoxime (2-PAM). Meanwhile, unlike 2-PAM, in vivo study showed that the lead compound 5b is able: (1) to reactivate POX-inhibited AChE in the brain; (2) to decrease death of neurons and, (3) to prevent memory impairment in rat model of POX-induced neurodegeneration.

Chronic ghrelin administration restores hippocampal long-term potentiation and ameliorates memory impairment in rat model of Alzheimer's disease.

Alzheimer's disease (AD), as a common age-related dementia, is a progressive manifestation of cognitive decline following synaptic failure resulted majorly by senile plaques composed of deposits of amyloid beta (Aβ). Ghrelin is a multifunctional peptide hormone with receptors present in various brain tissues including hippocampus and has been associated with neuroprotection, neuromodulation, and memory processing. Here, we investigated the neuroprotective and therapeutic effects of intracerebroventricular (icv) ghrelin infusion for 2 weeks on passive avoidance learning (PAL), memory retention, and synaptic plasticity in the hippocampal dentate gyrus (DG) and CA1 of both normal rats and Aβ1-42-induced neurotoxicity in AD model. Male Wistar rats were evaluated for their passive memory performance using a shuttle box while some groups had already received Aβ1-42 and/or chronic ghrelin. Using field potential recording, the induction of short- and long-term potentiation (STP and LTP) was studied in DG granule cells along with the LTP changes in CA1 pyramidal neurons through stimulation of the medial perforant path (mPP) and Schaffer collaterals (SCs), respectively. Our results demonstrated that chronic ghrelin treatment not only improved memory processing and retrieval in normal rats during the PAL task, but also promoted memory retention and alleviated memory loss by amelioration of Aβ1-42-induced synaptic plasticity impairment in AD subjects through augmentation of field excitatory postsynaptic potential (fEPSP) slope that led to LTP restitution in both the mPP-DG and the CA3-CA1 synapses. Meanwhile, STP was not significantly changed, meaning that although ghrelin enhanced postsynaptic excitability in DG, it did not change presynaptic transmitter release significantly. This suggests the involvement of postsynaptic mechanisms in long-term ghrelin-enhanced memory. In conclusion, it can be inferred that chronic ghrelin administration has an auspicious therapeutic value for impaired cognitive performance and memory deficits in AD-like neuropathology.

Key mechanisms underlying netrin-1 prevention of impaired spatial and object memory in Aβ1-42 CA1-injected rats.

Alzheimer's disease (AD) is a neurodegenerative disorder with an incompletely defined aetiology that is associated with memory and cognitive impairment. Currently available therapeutics only provide temporary assistance with symptoms. In spite of plentiful research in the field and the generation of thousands of studies, much is still to be clarified on precise mechanisms of pathobiology, prevention modalities, disease course and cure. Netrin-1, a laminin family protein, is said to have anti-inflammatory and anti-apoptotic effects and has a key role in neurogenesis and morphogenesis of neural structures. Accordingly, this study was designed to investigate protective effects of bilateral intrahippocampal fissure microinjections of netrin-1 on memory impairment in rat model of AD. Concomitant administration of netrin-1 with amyloid beta 1-42 (Aβ1-42 ) improved cognitive dysfunction in novel object recognition task (NOR), ameliorated impaired spatial memory in Morris water maze (MWM) setting, increased neuronal density and reduced amyloid aggregation in rat AD model. Netrin-1 was also seen to prevent Aβ1-42 -induced caspase-3, caspase-7 and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation. Therefore, based on the data reported here, netrin-1 may be a promising biologic therapeutic that addresses the memory and neuronal loss associated with AD.

帕金森病模型大鼠学习记忆能力变化的观察

[目的]利用Morris水迷宫、避暗箱、穿梭箱检测6-羟多巴胺(6-OHDA)致帕金森病(PD)模型大鼠学习记忆的能力，了解PD除行为障碍外的认知变化，并运用大鼠脑内酪氨酸羟化酶(tyrosine hydroxylase, TH)表达量检测的方法来对PD大鼠模型进行检验和评价。[方法]实验分为PD模型组和正常对照组。首先以立体定位单侧纹状体注射6-OHDA法制备PD大鼠模型，2周后腹腔注射阿扑吗啡(APO)诱导转圈，旋转圈数 > 7 r/min的大鼠判定为成功PD模型，并运用大鼠脑内酪氨酸羟化酶(tyrosine hydroxylase, TH)表达量检测的方法来对PD大鼠模型进行检验和评价。应用Morris水迷宫测定大鼠的目标象限游泳路程及目标象限游泳时间；采用大鼠避暗箱进行多次测试法，获取并分析明箱观察时间百分比(%)数据；应用大鼠穿梭箱进行穿梭箱被动回避反应，获取并分析主动逃避次数(次)和主动逃避平均时间(秒)。[结果] PD模型组大鼠和正常对照组相比，Morris水迷宫实验中，象限游泳路程显著减少(p < 0.05)，目标象限游泳时间极显著减少(p < 0.01)；避暗箱进行多次测试法中，明箱观察时间百分比(%)明显缩短(p < 0.05)；穿梭箱被动回避反应实验中，主动逃避次数(次)和主动逃避平均时间(秒)均明显减少(p < 0.05)。[结论] 6-OHDA纹状体注射构建的PD大鼠的学习记忆能力明显降低，可以作为研究人类帕金森病性痴呆的模型。 [Aim] To evaluate the learning and memory impairment in rat model of Parkinson disease (PD) which established by injection of 6-hydroxydopamine (6-OH) at different stages with Morris maze, passive avoidance test and active avoidance test. [Methods] Rats were grouped into two: PD model rats and Normal rats. The unilateral stereotaxic intra-striatal single point injection of 6-hydroxy- dopamine (6-OH) was adopted to establish PD model rats. The rats were induced to rotate by in-jecting apomorphine (APO) while 2 weeks after operation, in order to screen the successful PD rat model. The number of rotations for the successful PD model rats is greater than 7 r/min. Measuring the distance and the time that the rats stayed the quadrant of the platform with Morris maze. Application of rats box for the shuttle box passive avoidance response, acquisition and analysis of the number of active escapes and takes the initiative to escape the average time(s). [Results] In Morris maze, PD model rats compared with the normal control rats, quadrant swimming distance decreased significantly (P < 0.05) and the swimming time in target quadrant was reduced (P < 0.01) significantly; passive avoidance test for multiple testing method, camera lucida observation time percentage (%) was significantly shortened (P < 0.05). [Conclusion] The learning and memory ability of PD rats which were constructed by striatal injection of 6-OHDA was significantly reduced, and it can be used as a model for the study of Parkinson’s disease dementia.

Effect of Rheum Ribes Hydro-Alcoholic Extract on Memory Impairments in Rat Model of Alzheimer's Disease.

Some animal models have been used to study Alzheimer's disease (AD). AD is an irreversible progressive neurodegenerative disease and the most common cause of dementia. Animal studies have shown that there is a relation between decrease in cholinergic functions in the nucleus basalis of Meynert (NBM) and loss of learning capability and memory. The aim of this study was to investigate the effect of Rheum ribes extract (RR) on memory deficit in one of the rat models of AD. Plant (1500gr) was collected from Saman (kahkesh) region of Chaharmahal Va Bakhtiari province in Iran. RR hydro-alcoholic extracts were prepared using maceration method. Rat model of Alzheimer was induced by Nucleus Basalis of Meynert lesions (NBML). Animals (n = 32) received extracts for 20 days and then passive avoidance and Morris water maze tasks were performed for memory evaluation. FRAP and HPLC methods were used for measurement of the antioxidant and Malondialdehyde (MDA) levels in blood. In water maze experiment, probe trial results showed that NBML group spent significantly less time in target quadrant, in which the platform was located on the preceding day. In addition, the time spent in target quadrant was significantly increased in NBML + RR groups (250 and 500 mg/kg) compared to the NBML group. In passive avoidance task, mean initial latency time and step-though latency were significantly decreased in NBML group. RR extracts significantly prolonged step-through latency in NBML + RR groups. Results of this study suggest that Rheum ribes extracts can improve memory deficits induced by bilateral NBM lesions in rats.