Scopolamine-induced Rats Research Articles

Effects of aqueous extract of ocimum gratissimum and momordica charantia on learning and memory in scopolamine-induced dementia rats model

Effects of aqueous extract of ocimum gratissimum and momordica charantia on learning and memory in scopolamine-induced dementia rats model

Caffeine improves sperm quality, modulates steroidogenic enzyme activities, restore testosterone levels and prevent oxidative damage in testicular and epididymal tissues of scopolamine-induced rat model of amnesia.

This study was designed to assess the role of caffeine on fertility parameters in testicular and epididymal tissues of scopolamine-induced model of amnesia in rats. Adult male rats were treated with scopolamine with or without caffeine. The modulatory effects of caffeine or scopolamine on fertility parameters were assessed in rats' testicular and epididymal homogenates. Scopolamine-induced sperm abnormalities, reduced steroidogenic enzyme 3β-Hydroxysteroid dehydrogenase (3β-HSD) and 17β-Hydroxysteroid dehydrogenase (17β-HSD) activities and serum testosterone levels in rats' testicular tissues. Treatment with caffeine increased 3β-HSD and 17β-HSD as well as testosterone levels. Caffeine also reversed sperm viability, sperm motility and sperm count in testicular tissues of scopolamine-treated rats. Furthermore, scopolamine-induced oxidative damage in rats' epididymal and testicular tissues via reduction of thiol and non-protein thiol content as well as increase in reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Caffeine attenuated oxidative stress in testicular and epididymal tissues of rats treated with scopolamine via increase in non-protein and protein thiol levels with concomitant reduction in ROS and MDA levels. This study revealed that caffeine (5 and 25mg/kg) improved sperm quality, increased steroidogenic enzyme activities and attenuated oxidative damage in testis and epididymis of rats treated with scopolamine.

치매모델 쥐의 과제지향 훈련이 인지기능 회복과 중추신경계 가소성에 미치는 영향

치매모델 쥐의 과제지향 훈련이 인지기능 회복과 중추신경계 가소성에 미치는 영향

Reduced systemic exposure and brain uptake of donepezil in rats with scopolamine-induced cognitive impairment

1. Donepezil (DPZ) is an acetylcholinesterase (AchE) inhibitor used in the mild to moderately severe Alzheimer’s disease. Among its major metabolites, 6-O-desmethyl DPZ (6-DDPZ), 5-O-desmethyl DPZ (5-DDPZ) and DPZ N-oxide, the anti-AchE activities of 5-DDPZ and DPZ N-oxide have never been clearly identified before. Besides, there is no report on simultaneous determination of DPZ and its three metabolites in the brain, thus their uptake in hippocampus and cortex are unknown. Therefore, the current studies are proposed aiming to: (1) investigate the anti-AchE activities and brain uptake of DPZ and its three metabolites and (2) compare their pharmacokinetics and brain uptake between normal and scopolamine-induced rats.2. DPZ and its three metabolites demonstrated anti-AchE activities with the IC50 in the order of DPZ (7.20 × 10−2 μM), 6-DDPZ (1.14 × 10−1 μM), 5-DDPZ (4.03 × 10−1 μM) and DPZ N-oxide (1.61 μM). They were also evenly distributed in the brain and retained much longer in the brain than that in plasma in normal rats.3. Compared to normal rats, Cmax, AUC0→24h and AUC0→∞ of DPZ were reduced by 52.0%, 31.2% and 30.1%, respectively; Tmax of DPZ and its three metabolites were prolonged and their brain uptake were decreased in scopolamine-induced rats, suggesting the potential reduced absorption of DPZ.

Neuroprotective Effects of Red Ginseng Saponins in Scopolamine-Treated Rats and Activity Screening Based on Pharmacokinetics.

Ginseng has been used to alleviate age-related dementia and memory deterioration for thousands of years. This study investigated the protective effect of red ginseng saponins against scopolamine-induced cerebral injury. Meanwhile, pharmacokinetics of ginsenosides in normal and scopolamine-treated rats were compared. After scopolamine injection, glutathione, catalase and superoxide dismutase levels were significantly decreased when compared with control group. Compared with SA group, pretreatment of rats with red ginseng saponins could increase glutathione, catalase and superoxide dismutase level. Treatment with red ginseng saponins significantly decreased malondialdehyde level. In the pharmacokinetic analysis, a pattern recognition analysis method was used to investigate the pharmacokinetics of the absorbed compounds in blood. The pharmacokinetic parameters of Rg1, Rg2, Rh3, Rg5 and Rk1 in model group had higher area under the curve (AUC), mean residence time (MRT) and peak plasma concentration (Cmax) values; area under the curve (AUC) values and peak plasma concentration (Cmax) of model group was significantly different from that of normal group (p < 0.05). The Cmax value of Rk3, Rh1, Rh2 and Rh4 in model group was higher than normal group, but their AUC values were not significantly different. There was no significantly difference in time at Cmax (Tmax), AUC and Cmax values of Rb1, Rb2 Re, Rc, Rd and Rf between the model and normal group. 16 ginsenosides were grouped into three separate clusters according to principal component analysis (PCA) score plot based on pharmacokinetic data. The results suggested red ginseng saponins have significant protective effect against scopolamine-induced memory deficit and scopolamine-induced rats could lead to the changes of pharmacokinetic behaviors of ginsenosides.

Pharmacological evaluation of Hibiscus abelmoschus against scopolamine-induced amnesia and cognitive impairment in mice

Objective: Progressive loss of memory has a prominent role in devastating neurodegenerative diseases such as amnesia, dementia and Alzheimer's disease. The present study was, thus, designed to investigate the potential of Hibiscus abelmoschus (H. abelmoschus) in scopolamine-induced amnesic Swiss Albino mice. Materials and Methods: Phytochemical and acute toxicity studies of H. abelmoschus ethanolic extract (HAEE) were performed. Memory loss was induced by scopolamine (1 mg/kg, i.p), a muscarinic antagonist, and evaluated by using Morris water maze (MWM), elevated plus maze (EPM) and modified passive avoidance tests on Swiss Albino mice. Besides this, locomotor activity, serum biochemical parameters such as total cholesterol and triglyceride levels were evaluated. Lipid peroxidation (LPO), glutathione (GSH) level and catalase (CAT) activity were also checked. HAEE at a dose of 200 and 400 mg/kg body weight administered orally to the animals. Donepezil hydrochloride (1 mg/kg) was taken as standard. Results: Pre-treatment of mice with HAEE significantly reversed scopolamine-induced memory impairments, as evidenced by a significant decrease in escape latency in the MWM task, transfer latency in EPM task and an increase in step-down latency in the modified passive avoidance task. HAEE also exhibited a remarkable cholesterol and triglyceride-lowering property in the present study. Moreover, treatment with HAEE (200 and 400 mg/kg, p.o) to scopolamine-induced rats significantly decreased the LPO and increased the GSH and catalase levels. Conclusion: The memory restorative effects of H. abelmoschus in amnesia may involve its multiple functions including antioxidative and lipid-lowering properties and the presence of phytoconstituents. Thus, H. abelmoschus may act as memory enhancer and may also be useful as a supportive adjuvant in the treatment of impaired memory functions.

Saraswatarishta reverses neuronal injury in brain tissues of scopolamine-induced rat model

Introduction: Neuroinflammation has been implicated in the pathogenesis or the progression of the variety of acute and chronic neurological and neurodegenerative disorders, including Alzheimer's disease. The Saraswatarishta is an Ayurvedic medicine utilized in many health conditions such as anti-aging, to improve memory, immunity, and quality of semen and sperms to treat epilepsy and cosmetic use for skins. It is a liquid Ayurvedic medicine. Saraswatarishta contains 5%–10% of self-produced alcohol in it, which serves as a vehicle to deliver water- and alcohol-soluble active herbal components to the body. It is also called Sarasvatarishtam. The aim of this study was to find the possible neuroprotective role of Saraswatarishtam as a preventive Ayurveda and Siddha drug to hamper cholinergic dysfunctions and histopathological changes in scopolamine-treated rat model. Material and Methods: The compound Saraswatarishtam was obtained from standard Ayurvedic vendor at Chennai. Group 1 – normal control animals received normal saline for 8 continuous days. Group 2 – positive control treated with scopolamine (0.4 mg/kg). Group 3 – received 200 mg/kg of piracetam for 8 continuous days. Group 4 and Group 5 served as a test and received 200 mg/kg and 400 mg/kg of Saraswatarishtam, respectively, for 8 continuous days. On the 8th day, after 90 min of drug administration, Group 2, Group 3, Group 4 and Group 5, were treated with 0.4 mg/kg of scopolamine. Brain tissues were dissected out and analyzed for histopathological changes after sacrifice with high dose of halothane. Results: Administration of scopolamine produced marked focal gliosis with mononuclear infiltration. The hippocampal region showed neuronal degeneration with sclerosis. Piracetam treated group showed pyknotic nucleus in neurons of the cerebral cortex and mild edema. Low dose (200 mg/kg) treatment with Saraswatarishtam followed by scopolamine administration showed moderate histopathological changes such as mild infiltration of monocytes but normal neuronal architecture. High dose (400 mg/kg) treatment with Saraswatarishtam followed by scopolamine administration shows abnormal morphology of cerebrum, cerebellum, basal nuclei, and hippocampus. Discussion and Conclusion: The results of the present study suggested that Saraswatarishtam exhibits neuroprotective properties against scopolamine-induced neuronal damage.

Evaluation of the protective effect of Myrtus communis in scopolamine-induced Alzheimer model through cholinergic receptors

Alzheimer's disease is a progressive neurodegenerative disorder causing common health problem with increasing age. Evidences show that the key symptoms of AD are mainly caused by cholinergic system dysfunction which has a role in cognitive disorders. Cholinergic pathways especially muscarinic receptors like M1 subtype also have a major role in learning, memory, cognitive functions and emotional state. There is no available permanent treatment currently to cure AD or to change its progression. This study was designed to investigate the factors that play important role in pathogenesis of AD and to compare the effects of Galantamine treatment with effects of Myrtus communis treatment. The expression level of M1, ACh, BDNF; AChE activity, GSH level, MDA and MPO activity and AChE gene expression were investigated in scopolamine-induced rat model. Results showed that, administration of MC significantly improves the SCOP-induced reduction of latency and object recognition time; increasing BDNF, M1 and ACh receptor expression levels in the different brain regions. Additionally, MC showed an increased in AChE by enhancing GSH activity and reducing MDA level and MPO activity. In conclusion MC considered as a possible novel therapeutic approach that can be a valuable alternative way in the prevention and treatment of AD.

Memory Enhancing, Anxiolytic and Antidepressant Effects of Achillea biebersteinii (Asteraceae) Essential Oil on Scopolamine-Induced Rats

The objective of this study was to evaluate the effects of inhaled Achillea biebersteinii Afan. (Asteraceae) essential oil on memory, anxiety and depression in scopolamine-induced amnesic rats. Six groups of adult female Wistar rats (3 months old) were used. These are, control group, Scopolamine - alone- treated group, diazepam alone-treated group, tramadol alone treated group, Sco + A. biebersteinii essential oil 1 % administrated group and Sco + A. biebersteinii essential oil 3 % administrated groups. Memory performances were assessed by Y-maze task and radial-arm maze task. Anxiety and depressive-like behavior were evaluated by elevated plus-maze and forced swimming tasks, respectively. The scopolamine-only administrated group showed impaired spatial memory as evidenced by decrease of the spontaneous alternation percentage in Y- maze test, and increase of the number of working and reference memory errors in the radial arm-maze test. In addition, scopolamine-only administrated group displayed increased anxiety and depressive-like behavior as evidenced by decrease of the exploratory activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming time and increase of immobility time within forced swimming test. Achillea biebersteinii essential oil significantly improved memory formation, and reduced anxiety and depression-like behavior in scopolamine-induced rats as compared to scopolamine-alone induced rats. The essential oil of this plant could be a good candidate for complementary therapy against neurological diseases like Alzheimer’s disease.

칼슘 배합 비율에 따른 초석잠의 scopolamine 치매유도 흰쥐에 대한 기억손상 개선 효과

칼슘 배합 비율에 따른 초석잠의 scopolamine 치매유도 흰쥐에 대한 기억손상 개선 효과

Influence of the Melissa officinalis Leaf Extract on Long-Term Memory in Scopolamine Animal Model with Assessment of Mechanism of Action.

Melissa officinalis (MO, English: lemon balm, Lamiaceae), one of the oldest and still most popular aromatic medicinal plants, is used in phytomedicine for the prevention and treatment of nervous disturbances. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 50% ethanol extract of MO leaves (200 mg/kg, p.o.) compared with rosmarinic acid (RA, 10 mg/kg, p.o.) and huperzine A (HU, 0.5 mg/kg, p.o.) on behavioral and cognitive responses in scopolamine-induced rats. The results were linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex of rats. In our study, MO and HU, but not RA, showed an improvement in long-term memory. The results were in line with mRNA levels, since MO produced a decrease of AChE mRNA level by 52% in the cortex and caused a strong significant inhibition of BACE1 mRNA transcription (64% in the frontal cortex; 50% in the hippocampus). However, the extract produced only an insignificant inhibition of AChE activity in the frontal cortex. The mechanisms of MO action are probably more complicated, since its role as a modulator of beta-secretase activity should be taken into consideration.

Neuroprotective Effect of &amp;lt;i&amp;gt;Phyllanthus acidus&amp;lt;/i&amp;gt; L. on Learning and Memory Impairment in Scopolamine-Induced Animal Model of Dementia and Oxidative Stress: Natural Wonder for Regulating the Development and Progression of Alzheimer’s Disease

Nature is the best source of complementary and alternative medicine. The plant Phyllanthus acidus (PA) L. has been used traditionally in pain, inflammatory and oxidative stress related disorders. In this consequence, methanolic extract of PA (MEPA) was selected to explore the ability of this plant to enhance cognitive function, brain antioxidant enzymes and anti-acetylcholinesterase activity which can be used for the treatment of oxidative stress related disorders like Alzheimer’s disease (AD). The purpose of this study was to investigate the neuroprotective effect of MEPA on learning and memory impairment in scopolamine-induced rats of dementia and oxidative stress. Treatment with MEPA (i.e., 100 and 200 mg/kg b.w.) was investigated in scopolamine-treated Swiss albino male rats for 14 days and its neuroprotective effects were examined using Elevated Plus Maze (EPM) test, Passive Avoidance (PA) test, Novel Object Recognition (NOR) test, Morris Water Maze (MWM) test as well as level of antioxidant enzymes such as catalase (CAT), super oxide dismutase (SOD), glutathione reductase (GSR), glutathione-S-transferase (GST), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), lipid peroxidation (TBARS) contents and acetylcholinesterase (AChE) activity in rat brain tissue homogenates. Administration of MEPA significantly (P < 0.05, P < 0.01; P < 0.01) decreased RTL (retention transfer latency) in rats on 7th and 14th day compared to the disease control and control group in the EPM test. In PA test the doses of MEPA suggestively (P < 0.05, P < 0.001; P < 0.05, P < 0.01) increased STL (step-through latency) in rats on 7th and 14th day with respect to disease control and control group. For NOR test administration of MEPA considerably (P < 0.01, P < 0.001; P < 0.01) increased the DI (discrimination index) in rats with respect to that of disease control and control group. The doses of MEPA markedly (P < 0.05, P < 0.01; P < 0.01) decreased EL (escape latency) and significantly (P < 0.01, P < 0.001; P < 0.05, P < 0.01) increased TSTQ (time spent in the target quadrant) on successive days as compared to that of disease control and control group in the acquisition trial of MWM test. In case of probe trial of MWM test MEPA administration considerably (P < 0.01; P < 0.05, P < 0.01) increased TSTQ and significantly (P < 0.05, P < 0.01; P < 0.05, P < 0.01) increased TSA (time spent in the annuli) in rats on successive days as compared to that of disease control and control group. MEPA administration significantly (P < 0.05, P < 0.01, P < 0.001; P < 0.05, P < 0.01) increased the level of CAT, SOD, GSR, GST GSH, GSH-Px and markedly (P < 0.01; P < 0.01, P < 0.001) decreased TBARS level through inhibiting lipid peroxidation as well as significantly (P < 0.01, P < 0.001; P < 0.05, P < 0.01, P < 0.001) decreasing AChE activity in rats brain compared to the disease control and control group. The present study demonstrates that MEPA showed the neuroprotective effect by improving cognitive functions and reduces oxidative stress by increasing the level of brain antioxidant enzymes as well as decreasing lipid peroxidation and acetylcholinesterase activity. Therefore, this plant extract can be used for enhancing learning, memory, antioxidant potentiality and anti-acetylcholinesterase activity in neurodegenerative disorders like AD.

Fornix deep brain stimulation enhances acetylcholine levels in the hippocampus.

Deep brain stimulation (DBS) of the fornix has gained interest as a potential therapy for advanced treatment-resistant dementia, yet the mechanism of action remains widely unknown. Previously, we have reported beneficial memory effects of fornix DBS in a scopolamine-induced rat model of dementia, which is dependent on various brain structures including hippocampus. To elucidate mechanisms of action of fornix DBS with regard to memory restoration, we performed c-Fos immunohistochemistry in the hippocampus. We found that fornix DBS induced a selective activation of cells in the CA1 and CA3 subfields of the dorsal hippocampus. In addition, hippocampal neurotransmitter levels were measured using microdialysis before, during and after 60 min of fornix DBS in a next experiment. We observed a substantial increase in the levels of extracellular hippocampal acetylcholine, which peaked 20 min after stimulus onset. Interestingly, hippocampal glutamate levels did not change compared to baseline. Therefore, our findings provide first experimental evidence that fornix DBS activates the hippocampus and induces the release of acetylcholine in this region.

Soybean and tempeh total isoflavones improved antioxidant activities in normal and scopolamine-induced rat brain

Soybean and tempeh total isoflavones improved antioxidant activities in normal and scopolamine-induced rat brain

Intraperitoneal Administration of a Novel TAT-BDNF Peptide Ameliorates Cognitive Impairments via Modulating Multiple Pathways in Two Alzheimer's Rodent Models.

Although Alzheimer’s disease (AD) has been reported for more than 100 years, there is still a lack of effective cures for this devastating disorder. Among the various obstacles that hold back drug development, the blood-brain barrier (BBB) is one of them. Here, we constructed a novel fusion peptide by linking the active domain of brain-derived neurotrophic factor (BDNF) with an HIV-encoded transactivator of transcription (TAT) that has a strong membrane-penetrating property. After intraperitoneal injection, the eGFP-TAT could be robustly detected in different brain regions. By using scopolamine-induced rats and APPswe mice representing AD-like cholinergic deficits and amyloidosis, respectively, we found that intraperitoneal administration of the peptide significantly improved spatial memory with activation of the TrkB/ERK1/2/Akt pathway and restoration of several memory-associated proteins in both models. Administration of the peptide also modulated β-amyloid and tau pathologies in APPswe mice, and it increased the amount of M receptor with modulation of acetylcholinesterase in scopolamine-induced rats. We conclude that intraperitoneal administration of our TAT-BDNF peptide could efficiently target multiple molecular pathways in the brain and improve the cognitive functions in AD-like rodent models.

The interaction between decreased short-term spatial memory and increased oxidative stress in a scopolamine-induced rat model of Alzheimer’s disease

The interaction between decreased short-term spatial memory and increased oxidative stress in a scopolamine-induced rat model of Alzheimer’s disease

Improvement in Long-Term Memory following Chronic Administration of Eryngium planum Root Extract in Scopolamine Model: Behavioral and Molecular Study.

Eryngium planum L. (EP) is as a rare medicinal plant with a lot of potentials as pharmaceutical crops. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 70% ethanol extract of EP roots (200 mg/kg, p.o.) on behavioral and cognitive responses in Wistar rats linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex. On the last day of experiment, 30 min after the last dose of EP or Huperzine A (HU), scopolamine (SC) was given at a dose of 0.5 mg/kg b.w. intraperitoneally. The results of a passive avoidance test showed an improvement in long-term memory produced by the EP extract in both scopolamine-induced rats and control group. EP caused an insignificant inhibition of AChE and BuChE activities in the frontal cortex and the hippocampus. EP decreased mRNA AChE, BuChE, and BACE-1 levels, especially in the cortex. Our results suggest that the EP extract led to the improvement of the long-term memory in rats coupled with total saponin content. The mechanism of EP action is probably complicated, since HPLC-MS analysis showed 64 chemical compounds (phenolics, saponins) in the extract of EP roots.

Rosmarinus officinalis L. leaf extract improves memory impairment and affects acetylcholinesterase and butyrylcholinesterase activities in rat brain

Rosmarinus officinalis L. leaf as part of a diet and medication can be a valuable proposal for the prevention and treatment of dementia. The aim of the study was to assess the effects of subchronic (28-fold) administration of a plant extract (RE) (200mg/kg, p.o.) on behavioral and cognitive responses of rats linked with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity and their mRNA expression level in the hippocampus and frontal cortex. The passive avoidance test results showed that RE improved long-term memory in scopolamine-induced rats. The extract inhibited the AChE activity and showed a stimulatory effect on BuChE in both parts of rat brain. Moreover, RE produced a lower mRNA BuChE expression in the cortex and simultaneously an increase in the hippocampus. The study suggests that RE led to improved long-term memory in rats, which can be partially explained by its inhibition of AChE activity in rat brain.

Biochemical basis of scopolamine-induced rat amnesia: Behavioral, [formula omitted] receptor autoradiographical, and biochemical analysis

Biochemical basis of scopolamine-induced rat amnesia: Behavioral, [formula omitted] receptor autoradiographical, and biochemical analysis

Biochemical basis of scopolamine-induced rat amnesia: Behavioral, [formula omitted] receptor autoradiographical, and biochemical analysis

Biochemical basis of scopolamine-induced rat amnesia: Behavioral, [formula omitted] receptor autoradiographical, and biochemical analysis