Latency In Passive Avoidance Test Research Articles

Protective effects of Buxus hyrcana against memory impairment and oxidative stress in a pentylenetetrazole-kindled epileptic rat model

Pentylenetetrazole (PTZ) is a chemical substance which is largely used for the induction of seizure and epilepsy in the animal model, and it can also, disrupts free radicals balance and cause oxidative stress in the body with a negative impact on memory and learning. In this study, the medicinal plant Buxus hyrcana, was used to evaluate its effect on oxidative stress and memory deficit caused by PTZ in the rats. Twenty-four rats were randomly allocated to 4 groups: control negative under treatment with PTZ (sub-threshold dose 35 mg/kg for one month), control positive under treatment with phenobarbital (PB-30 mg/kg), and two PTZ groups under treatment with B. hyrcana extract (BHE-300, and -600 mg/kg). Standard passive avoidance test was used to evaluate retention and recall (evaluation of memory and learning). After behavioral evaluation, rats were anesthetized, brains were removed, and following preparation of brain homogenates, oxidative stress was evaluated using specified methods. Step-through latency in passive avoidance test in the BHE receiving group was greater than PTZ group (p<0.001). In addition, brain lipid peroxidation malondialdehyde (MDA) and nitric oxide (NO) level in BHE-treated group was significantly lower (p<0.001) and the reduced glutathione (GSH) activity levels were significantly greater versus PTZ group (p<0.001). Our results showed that BHE could prevent memory deficit and ameliorate oxidative stress in the PTZ-kindled rats.

Protective effects of Buxus hyrcana against memory impairment and oxidative stress in a pentylenetetrazole-kindled epileptic rat model

Pentylenetetrazole (PTZ) is a chemical substance which is largely used for the induction of seizure and epilepsy in the animal model, and it can also, disrupts free radicals balance and cause oxidative stress in the body with a negative impact on memory and learning. In this study, the medicinal plant Buxus hyrcana, was used to evaluate its effect on oxidative stress and memory deficit caused by PTZ in the rats. Twenty-four rats were randomly allocated to 4 groups: control negative under treatment with PTZ (sub-threshold dose 35 mg/kg for one month), control positive under treatment with phenobarbital (PB-30 mg/kg), and two PTZ groups under treatment with B. hyrcana extract (BHE-300, and -600 mg/kg). Standard passive avoidance test was used to evaluate retention and recall (evaluation of memory and learning). After behavioral evaluation, rats were anesthetized, brains were removed, and following preparation of brain homogenates, oxidative stress was evaluated using specified methods. Step-through latency in passive avoidance test in the BHE receiving group was greater than PTZ group (p<0.001). In addition, brain lipid peroxidation malondialdehyde (MDA) and nitric oxide (NO) level in BHE-treated group was significantly lower (p<0.001) and the reduced glutathione (GSH) activity levels were significantly greater versus PTZ group (p<0.001). Our results showed that BHE could prevent memory deficit and ameliorate oxidative stress in the PTZ-kindled rats.

Protective effects of Buxus hyrcana against memory impairment and oxidative stress in a pentylenetetrazole-kindled epileptic rat model

Pentylenetetrazole (PTZ) is a chemical substance which is largely used for the induction of seizure and epilepsy in the animal model, and it can also, disrupts free radicals balance and cause oxidative stress in the body with a negative impact on memory and learning. In this study, the medicinal plant Buxus hyrcana, was used to evaluate its effect on oxidative stress and memory deficit caused by PTZ in the rats. Twenty-four rats were randomly allocated to 4 groups: control negative under treatment with PTZ (sub-threshold dose 35 mg/kg for one month), control positive under treatment with phenobarbital (PB-30 mg/kg), and two PTZ groups under treatment with B. hyrcana extract (BHE-300, and -600 mg/kg). Standard passive avoidance test was used to evaluate retention and recall (evaluation of memory and learning). After behavioral evaluation, rats were anesthetized, brains were removed, and following preparation of brain homogenates, oxidative stress was evaluated using specified methods. Step-through latency in passive avoidance test in the BHE receiving group was greater than PTZ group (p<0.001). In addition, brain lipid peroxidation malondialdehyde (MDA) and nitric oxide (NO) level in BHE-treated group was significantly lower (p<0.001) and the reduced glutathione (GSH) activity levels were significantly greater versus PTZ group (p<0.001). Our results showed that BHE could prevent memory deficit and ameliorate oxidative stress in the PTZ-kindled rats.

Inhibition of Ferroptosis Using UAMC‐3203 in the Post‐stroke Period Does Not Impact Cognitive Outcomes in Diabetic Rats

IntroductionPost‐stroke cognitive impairment (PSCI) contributes to significant long‐term disability in stroke victims. 30% of ischemic stroke victims in the United States also have diabetes, which increases the risk of hemorrhagic transformation as well as PSCI. Ferroptosis, an iron‐induced cell death can instigate increased oxidative stress and contribute to impaired neurovascular repair leading to PSCI in diabetes. In our previous studies, we were able to identify that treating diabetic animals with an iron chelator, deferoxamine (DFX), prevents post‐stroke vasoregression and improves functional outcomes. Furthermore, DFX prevented the activation of ferroptosis in brain microvascular endothelial cells in vitro. Untreated diabetic animals experienced progressive cognitive decline while being monitored for 8 weeks. These findings led us to speculate that endothelial ferroptosis also plays a role in vasoregression and impacts cognitive outcomes post‐stroke. Therefore, this study was designed to test the hypothesis that inhibiting ferroptosis in the post‐stroke period will improve cognitive recovery in diabetic animals.MethodsAnimals were housed in reverse light cycle. 8 weeks after diabetes onset, male rats underwent 60 min middle cerebral artery occlusion (MCAO). On Day 3, after stroke injury was confirmed by MRI, animals were randomized to UAMC‐3 (2mg/kg) or vehicle treatment for 2 weeks. Sensorimotor and cognitive behavioral tests were performed during the animals’ active hours up to 8 weeks post MCAO.Results(Table 1): 60 min occlusion caused significant acute neurological deficits. There were no differences between the groups in indices measured by novel object recognition (NOR), Y‐maze and sucrose preference tests. Interestingly, step through latency in passive avoidance test (PAT) was lower in the UAMC‐3203 group.ConclusionTreatment with a ferroptosis inhibitor for 2 weeks after stroke did not impact recognition and working memory but worsened aversive learning in diabetic male rats. Unlike our previous study in which behavior tests were performed during rats’ passive hours, there was no progressive cognitive decline in untreated animals. Further evaluation of behavior testing times as well as tissue markers of neurovascular degeneration, inflammation and ferroptosis are required to determine whether molecular and cellular markers are affected by the treatment before overt changes in behavioral outcomes.

Nobiletin prevents amyloid β1-40-induced cognitive impairment via inhibition of neuroinflammation and oxidative/nitrosative stress.

Alzheimer's disease (AD) is presented as an age-related neurodegenerative disease with multiple cognitive deficits and amyloid β (Aβ) accumulation is the most important involved factor in its development. Nobiletin is a bioflavonoid isolated from citrus fruits peels with anti-inflammatory and anti-oxidative activity as well as anti-dementia property that has shown potency to ameliorate intracellular and extracellular Ab. The aim of the present study was to assess protective effect of nobiletin against Aβ1-40-induced cognitive impairment as a consistent model of AD. After bilateral intrahippocampal (CA1 subfield) injection of Aβ1-40, rats were treated with nobiletin (10mg/kg/day; p.o.) from stereotaxic surgery day (day 0) till day + 7. Cognition function was evaluated in a battery of behavioral tasks at week 3 with final assessment of hippocampal oxidative stress and inflammation besides Nissl staining and 3-nitrotyrosine (3-NT) immunohistochemistry. Analysis of behavioral data showed notable and significant improvement of alternation in Y maze test, discrimination ratio in novel object recognition task, and step through latency in passive avoidance test in nobiletin-treated Aβ group. Additionally, nobiletin treatment was associated with lower hippocampal levels of MDA and ROS and partial reversal of SOD activity and also improvement of Nrf2 with no significant effect on GSH and catalase. Furthermore, nobiletin attenuated hippocampal neuroinflammation in Aβ group as shown by lower tissue levels of TLR4, NF-kB, and TNFa. Histochemical findings showed that nobiletin prevents CA1 neuronal loss in Nissl staining in addition to its alleviation of 3-nitrotyrosine (3-NT) immunoreactivity as a marker of nitrosative stress. Collectively, these findings indicated neuroprotective and anti-dementia potential of nobiletin that is partly attributed to its anti-oxidative, anti-nitrosative, and anti-inflammatory property associated with proper modulation of TLR4/NF-kB/Nrf2 pathways.

Ameliorative potential of phloridzin in type 2 diabetes-induced memory deficits in rats

Diabetes associated oxidative stress and impaired cholinergic neurotransmission causes cognitive deficits. Although phloridzin shows antioxidant- and insulin sensitizing-activities, its ameliorative potential in diabetes-induced memory dysfunction remains unexplored. In the present study, type 2 diabetes (T2D) was induced by streptozotocin (35 mg/kg, intraperitoneal) in rats on ad libitum high-fat diet. Diabetic animals were treated orally with phloridzin (10 and 20 mg/kg) for four weeks. Memory functions were evaluated by passive avoidance test (PAT) and novel object recognition (NOR) test. Brains of rats were subjected to biochemical analysis of glutathione (GSH), brain-derived neurotrophic factor (BDNF), malonaldehyde (MDA) and acetylcholinesterase (AChE). Role of cholinergic system in the effects of phloridzin was evaluated by scopolamine pre-treatment in behavioral studies. While diabetic rats showed a significant decrease in step through latency in PAT, and exploration time and discrimination index in NOR test; a substantial increase in all parameters was observed following phloridzin treatment. Phloridzin reversed abnormal levels of GSH, BDNF, MDA and AChE in the brain of diabetic animals. Moreover, in silico molecular docking study revealed that phloridzin acts as a potent agonist at M1 receptor as compared to acetylcholine. Viewed collectively, reversal of T2D-induced memory impairment by phloridzin might be attributed to upregulation of neurotrophic factors, reduced oxidative stress and increased cholinergic signaling in the brain. Therefore, phloridzin may be a promising molecule in the management of cognitive impairment comorbid with T2D.

Effects of Tanacetum polycephalum on passive avoidance learning and oxidative stress in epileptic model of memory impairment in the male Wistar rats

In the present study, the medicinal plant Tanacetum polycephalum, was used to evaluate its effect on oxidative stress and memory deficit caused by PTZ in the rats. Twenty-four rats were randomly categorized into four groups: control negative under treatment with PTZ (sub-threshold dose 35 mg kg−1 for 1 month), control positive under treatment with phenobarbital (PB 30 mg kg−1), and two PTZ groups under treatment with T. polycephalum extract (TPE 300, and 600 mg kg−1). Standard passive avoidance test was used to evaluate memory and learning. After behavioral evaluation, the rats were anesthetized and their brains were removed; following the preparation of brain homogenates, oxidative stress parameters were evaluated using specified methods. It was found that step-through latency in passive avoidance test in PTZ group receiving TPE was greater than that of PTZ group. In addition, brain lipid peroxidation (malondialdehyde) and nitric oxide level in TPE-treated group was significantly lower and glutathione activity and superoxide dismutase level were significantly greater in comparison to PTZ group. Our results showed that TPE could prevent memory deficit and ameliorate hippocampal oxidative stress in PTZ-kindled rats.

Annona atemoya Leaf Extract Improves Scopolamine-Induced Memory Impairment by Preventing Hippocampal Cholinergic Dysfunction and Neuronal Cell Death.

We explored the preventative effect of Annona atemoya leaf (AAL) extract on memory impairment in a scopolamine (SCO)-induced cognitive deficit mouse model. Fifty-eight mice were randomly divided into six groups and orally treated with AAL extract at (50, 100, or 200 mg/kg) or tacrine (TAC) for 21 days. Memory deficits were induced by a single injection of 1 mg/kg SCO (i.p.) and memory improvement was evaluated by using behavioral tests such as the passive avoidance task and Y-maze test. The levels of cholinergic functions, neuronal cell death, reactive oxygen species, and protein expression related to hippocampal neurogenesis were examined by immunohistochemical staining and western blotting. The administration of AAL extract improved memory impairment according to increased spontaneous alternation in the Y-maze and step-through latency in passive avoidance test. AAL extract treatment increased the acetylcholine content, choline acetyltransferase, and acetylcholinesterase activity in the hippocampus of SCO-stimulated mice. In addition, AAL extract attenuated oxidative stress-induced neuronal cell death of hippocampal tissue. In terms of the regulatory mechanisms, AAL extract treatment reversed the SCO-induced decreases in the expression of Akt, phosphorylation of cAMP response element binding protein, and brain-derived neurotrophic factor. Our findings demonstrate that AAL extract has the ability to alleviate memory impairment through preventative effect on cholinergic system dysfunction and oxidative stress-related neuronal cell death in a SCO-induced memory deficit animal model. Overall, AAL may be a promising plant resource for the managing memory dysfunction due to neurodegenerative diseases, such as Alzheimer’s disease (AD).

Neuroprotective Effect and Molecular Mechanism of [6]-Gingerol against Scopolamine-Induced Amnesia in C57BL/6 Mice.

We have investigated the neuroprotective and memory enhancing effect of [6]-gingerol (GIN), a pungent ingredient of ginger, using an animal model of amnesia. To determine the neuroprotective effect of GIN on cognitive dysfunction, scopolamine (SCO, 1 mg/kg, i.p.) was injected into C57BL/6 mice, and a series of behavioral tests were conducted. SCO-induced behavior changes and memory impairments, such as decreased alteration (%) in Y-maze test, increased mean escape latency in water maze test, diminished step-through latency in passive avoidance test, and shortened freezing time in fear condition test, were significantly prevented and restored by the oral administration of GIN (10 or 25 mg/kg/day). To further verify the neuroprotective mechanism of GIN, we have focused on the brain-derived neurotrophic factor (BDNF). The administration of GIN elevated the protein expression of BDNF, which was mediated via the activation of protein kinase B/Akt- and cAMP-response element binding protein (CREB) signaling pathway. These results suggest that GIN may have preventive and/or therapeutic potentials in the management of memory deficit and cognitive impairment in mice with amnesia.

Characterization of Cognitive Impairment in Type 2 Diabetic Rats

Among all the secondary complications of type 2 diabetes, cognitive impairment associated with diabetes is less well studied and characterized. We made an attempt to investigate the molecular mechanisms involved in cognitive decline in high fat diet-streptozotocin model of type 2 diabetes. High-fat diet and a single low dose streptozotocin (25 mg/kg) were used to induce diabetes in Sprague-Dawley rats. Developments of cognitive deficit in these animals were measured using change in transfer latency in elevated plus maze test and step-down latency in passive avoidance test. This was followed by biochemical estimation of acetylcholinesterase and reduced glutathione levels followed by histological evaluation of cortical and hippocampal slices. The high fat diet-streptozotocin animals developed type 2 diabetes, characterized by an increase in fasting blood glucose levels >250 mg/kg, marked increase (P<0.001) in triglyceride (207±7.2) and total cholesterol level (125.3±2.7) with a decrease (P<0.001) in high-density lipoproteins (14.27±1.1) when compared to control animals. After 4 weeks of development of type 2 diabetes high fat diet-streptozotocin animals showed signs of cognitive deficit with a significant decline in step-down latency (P<0.001) and a significant increase in transfer latency (P<0.001) compared to controls. The high fat diet-streptozotocin animals also showed significant decrease (P<0.001) in cortico-hippocampal glutathione levels and increase in (P<0.001) acetylcholinesterase activity as compared to control animals suggesting type 2 diabetes-associated oxidative stress and decrease in hippocampal Ach activity. Immunohistochemical studies in these animals showed pronounced astrogliosis and microglial activation in the cortical and hippocampal slices suggesting neuroinflammatory changes. We also found significant loss (P<0.001) of hippocampal neurons at CA1 and CA3 region in the diabetic rats as compared with healthy controls. Antidiabetic compound glibenclamide (10 mg/kg for 3 weeks) partly reversed the above neurobehavioral, biochemical and histological changes in the diabetic rat brain. Hence we show that high fat diet-streptozotocin type 2 diabetic rats may develop signs of cognitive impairment. This cognitive decline was found to be associated with an increase in acetylcholinesterase activity and loss of hippocampal neurons. Oxidative stress and neuroinflammatory changes in the brain of these animals may be responsible for hippocampal neuronal loss, which could be partly reversed upon glibenclamide treatment.

The total triterpenoid saponins of Xanthoceras sorbifolia improve learning and memory impairments through against oxidative stress and synaptic damage

BackgroundX. sorbifolia is a widely cultivated ecologicalcrop in the north of China which is used to produce biodiesel fuel. It also possesses special medicinal value and has attracted keen interests of researchers to explore its bioactivity. PurposeTo extract the total triterpenoid saponins from the husk of X. sorbifolia (TSX) and investigate its effects on Alzheimer's disease (AD). Study designTSX was prepared via modern extraction techniques. Its effects on two AD animal models, as well as the preliminary mechanism were investigated comprehensively. MethodsThe behavioral experiments including Y maze test, Morris water maze test and passive avoidance test were performed to observe the learning and memory abilities of the animals. ELISA assays, transmission electron microscope observation and Western blotting were employed in mechanism study. ResultsTSX, the main composition of X. sorbifolia, accounted for 88.77% in the plant material. It could significantly increase the spontaneous alternation in Y maze test (F (6, 65)=3.209, P<0.01), prolong the swimming time in the fourth quadrant in probe test of Morris water maze test (F (6, 71)=4.019, P<0.01), and increase the escape latency in passive avoidance test (F (6, 65)=3.684, P<0.01) in AD model animals. The preliminary mechanism research revealed that TSX could significantly increase the contents of hippocampal Ach and ChAT, and enhance activity of ChAT in hippocampus of quinolinic acid injected rats (F (5, 61)=3.915, P 0.01; F (5, 61)=3.623, P<0.01, F (5, 61)=4.344, P<0.01, respectively). It could also increase the activities of T-AOC and T-SOD, and decrease the content of MDA in hippocampus of Aβ1-42 injected mice (F (5, 30)=5.193, P<0.01, F (5, 30)=2.865, P<0.05, F (5, 30)=4.735, P<0.01, respectively). Moreover, it significantly increased the expressions of SYP, PSD-95 and GAP-43 in hippocampus (F (4, 27)=3.495, P<0.05; F (4, 27)=2.965, P<0.05; F (4, 27)=4.365, P<0.01, respectively), and improved the synaptic ultra-structure damage in model rats. ConclusionTSX could significantly improve the impairments of learning and memory. The preliminary mechanism might associate with its protection effects against oxidative stress damage, cholinergic system deficiency and synaptic damage. TSX are perfectly suitable for AD patients as medicine or functional food, which would be a new candidate to treat AD.

Sesame indicum, a nutritional supplement, elicits antiamnesic effect via cholinergic pathway in scopolamine intoxicated mice.

Present study was undertaken to evaluate the antiamnesic effect of Sesamum indicum (S. indicum) seeds (standardized for sesamin, a lignan, content) in scopolamine, a muscarinic antagonist intoxicated mice. Male Swiss albino mice (18-22 g bw) were pretreated with methanolic extract of sesame seeds (MSSE) (100 and 200 mg/kg/day, p.o) for a period of 14 days. Scopolamine (0.3 mg/kg, i.p.) was injected on day 14, 45 ± 10 min after MSSE administration. Antiamnesic effect of MSSE was evaluated using step-down latency (SDL) on passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. To unravel the mechanism of action, we examined the effects of MSSE on the genes such as acetyl cholinesterase (AChE), muscarinic receptor M1 subtype (mAChRM1 ), and brain derived neurotrophic factor (BDNF) expression within hippocampus of experimental mice. Further, its effects on bax and bcl-2 were also evaluated. Histopathological examination of hippocampal CA1 region was performed using cresyl violet staining. MSSE treatment produced a significant and dose dependent increase in step down latency in passive avoidance test and decrease in transfer latency in elevated plus maze in scopolamine intoxicated injected mice. MSSE down-regulated AChE and mAChRM1 and up-regulated BDNF mRNA expression. Further, it significantly down-regulated the bax and caspase 3 and up-regulated bcl-2 expression in scopolamine intoxicated mice brains. Mice treated with MSSE showed increased neuronal counts in hippocampal CA1 region when compared with scopolamine-vehicle treated mice. Sesame seeds have the ability to interact with cholinergic components involved in memory function/restoration and also an interesting candidate to be considered for future cognitive research. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1955-1963, 2016.

Protective Effect of Arabinoxylan against Scopolamine-Induced Learning and Memory Impairment.

The purpose of this study is to investigate the memory enhancing effect and underlying molecular mechanism of arabinoxylan (AX), a major component of dietary fiber in wheat against scopolamine (SCO)-induced amnesia in Sprague-Dawley (SD) rats. Diverse behavior tests including Y-maze, Morris water maze, and passive avoidance tests were performed to measure cognitive functions. SCO significantly decreased the spontaneous alterations in Y-maze test and step-through latency in passive avoidance test, whereas increased time spent to find the hidden platform in Morris water maze test compared with the sham control group. In contrast, oral administration of AX (25 mg/kg and 50 mg/kg) effectively reversed the SCO-induced cognitive impairments in SD rats. Furthermore, AX treatment up-regulated the expression of brain-derived neurotrophic factor (BDNF) in the cortex and hippo-campus via promoting activation of cAMP response element binding protein (CREB). Therefore, our findings suggest that AX can improve SCO-induced learning and memory impairment possibly through activation of CREB and up-regulation of BDNF levels, thereby exhibiting a cognition-enhancing potential.

Effects of 7-NI and ODQ on memory in the passive avoidance, novel object recognition, and social transmission of food preference tests in mice

BackgroundNitric oxide (NO) is an intercellular messenger that plays a critical role in learning and memory processes. Effects of nitric oxide synthase (NOS) inhibitors and guanylate cyclase (GC) inhibitors on cognitive function remain controversial.Material/MethodsThe aim of this study was to investigate effects of an NOS inhibitor, 7-nitroindazole (7-NI), and a GC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on different aspects of memory in passive avoidance (PA), novel object recognition (NOR), and social transmission of food preference (STFP) tests. Male Balb-c mice were treated intraperitoneally with 7-NI (15 mg/kg), ODQ (3,10 mg/kg), L-arginine (100 mg/kg) + 7-NI (15 mg/kg), or physiological saline.ResultsODQ (10 mg/kg) and 7-NI (15 mg/kg) significantly decreased second-day latency in PA test. 7-NI (15 mg/kg) and ODQ (10 mg/kg) significantly decreased the ratio index in the NOR test. 7-NI and ODQ (10 mg/kg) decreased cued/non-cued food eaten in STFP test. Amount of time spent in center zone significantly increased in ODQ (10 mg/kg) and 7-NI (15 mg/kg) groups in open field test, but there was no effect on total distance moved and speed of animals. ODQ (10 mg/kg) significantly increased number of entries into new compartments in exploratory activity apparatus, while 7-NI had no effect. Administration of L-arginine (100 mg/kg) before 7-NI reversed 7-NI-induced effects, supporting the role of NO in cognition.ConclusionsOur results confirm that inhibition of NO/cGMP/GS pathway might disturb emotional, visual, and olfactory memory in mice. Also, 7-NI and ODQ had anxiolytic effects in open field test, and ODQ also enhanced exploratory activity.

Beneficial effect of Brahmi Ghrita on learning and memory in normal rat.

Background:Learning, the process of acquiring memory such as behavioral change due to previous experiences and most intensively studied subjects in the field of neuroscience through various approaches to understand the mechanisms. Brahmi Ghrita (BG) was claimed for the treatment of learning and memory disorders in human being.Aim:To assess learning and memory activity of BG in normal rats.Materials and Methods:For this study, 24 rats were taken and divided into four groups (six in each). First group served as the control group, second and the third group as BG treated groups (400 and 800 mg/kg, p. o.) and the fourth group as standard drug (piracetam) 500 mg/kg, p.o. treated group. Learning and memory, activity of BG was evaluated in normal rats, using elevated maze plus and passive avoidance test.Results:BG and piracetam treated rats demonstrated a significant decrease in transfer latency in modified elevated plus maze test and increase in step through latency in passive avoidance test compared with control rats in a dose dependent manner. It may be due to increase in learning and memory. It was also reported that prolonged use of Bacopa monneri (L.) Pennell causes elevation of cerebral glutamic acid and transient increase in gamma aminobutaric acid, which may be helpful in the process of learning.Conclusion:Brahmi Ghrita enhances learning and memory as analogous to standard drug (piracetam) in normal rats.

Encouraging effect of Brahmi Ghrita in amnesia

Context: Brahmi Ghrita (BG) contains Brahmi (Bacopa monneri), Vacha (Acorus calamus), Kushtha (Saussurea lappa), Shankhapushpi (Convolvulus pluricaulis) and Puran Ghrita, prepared as per sneha paka process. Aim: The aim of this study was to assess the learning and memory activity of BG in Amnesic rats. Materials and Methods: The Learning and memory activity of BG (400 and 800 mg/kg, per oral) was evaluated in scopolamine (1 mg/kg, sub cutaneous) challenged rats, using elevated maze plus, passive avoidance test and active avoidance test. Results: BG treated scopolamine challenged rat demonstrated a significant decrease in transfer latency in modified elevated plus maze test and increase in step through latency in passive avoidance test compared to control rats in a dose dependent manner. BG treated rats took significant less number of total trials, shock trial and total time for jumping into safe compartment. Conclusion: BG antagonises the action of scopolamine. Key words: Brahmi Ghrita, modified elevated plus maze test, scopolamine

Combretum mucronatum and Capparis thonningii prevent scopolamine-induced memory deficit in mice

Context: Roots of Combretum mucronatum Schumach. & Thonn. (Combretaceae) and Capparis thonningii Schum. (Capparaceae) are used in southwest Nigeria in the treatment of inflammatory disorders and mental illness.Objective: This study evaluated the antidementic effect of the methanol root extracts of C. mucronatum and C. thonningii on scopolamine (3 mg/kg, i.p.) induced memory impairment in mice.Materials and methods: The effect of C. mucronatum and C. thonningii (50–200 mg/kg) administered orally for 3 days on memory impairments induced in mice by scopolamine was assessed in the passive avoidance and Morris water maze test and compared with that of tacrine (5 mg/kg, i.p.). The activities of acetylcholinesterase (AchE) and antioxidant enzymes were estimated in the brain after the completion of behavioral studies.Results: C. mucronatum and C. thonningii root extracts (50–200 mg/kg) reversed scopolamine-induced memory deficit with significant (p < 0.05) increase in transfer latency in passive avoidance test. Similarly, the extracts (200 mg/kg) ameliorated memory deficit as a result of significant (p < 0.001) decrease in escape latency and path length in Morris water maze test. The increased AChE activity induced by scopolamine was significantly (p < 0.05) inhibited by C. mucronatum and C. thonningii (100 and 200 mg/kg) treatment which was similar to the effect of tacrine. Both extracts significantly (p < 0.05) attenuated scopolamine-induced increase in oxidative stress parameters as well as restoration of glutathione activity.Discussion and conclusion: C. mucronatum and C. thonningii extracts possess significant anticholinesterase, antioxidant and antidementic properties, which may be useful in the management of Alzheimer’s disease.

Anticonvulsant and antioxidative activity of hydroalcoholic extract of tuber of Orchis mascula in pentylenetetrazole and maximal electroshock induced seizures in rats

Ethnopharmacological relevanceOrchis mascula tuber is used in many polyherbal formulations as a nerve tonic in India. Aim of the studyIn the present study, effect of hydroalcholic extract of O. mascula (HEOM) tuber was evaluated against seizures, seizure-induced oxidative stress and cognitive deficit in pentylenetetrazole and maximal electroshock-induced seizures in rats. Materials and methodsHEOM was administered orally 30min before induction of seizures by pentylenetetrazole (PTZ; 60mg/kg, i.p) or maximal electroshock (MES; 70mA). Elevated plus maze and passive avoidance tests were used to assess the learning and memory. Oxidative stress was studied by estimation of reduced glutathione and lipid peroxidation. Whole brain total cholinesterase activity was also evaluated. ResultsHEOM produced 33.3%, 50% and 66.7% protection in PTZ model and 16.7%, 16.7% and 33.3% at 250, 500 and 1000mg/kg, respectively, in MES-induced seizures. Pre-treatment with HEOM significantly decreased the retention transfer latency in elevated plus maze test, and an increase in the retention latency in passive avoidance test was observed. Oxidative stress induced by seizures was also attenuated as indicated by significant increase in GSH and decrease in MDA levels in HEOM treated groups. PTZ and MES caused a significant decrease in AChE and BChE activities, which was prevented by HEOM. ConclusionsHEOM thus showed protection against seizures, prevented the associated memory impairment probably by modulating cholinergic status and reducing oxidative stress.

PPARγ agonist pioglitazone improves scopolamine-induced memory impairment in mice

This study was conducted to evaluate the effects of exposure to pioglitazone, a peroxisome proliferator-activated receptor agonist, on cognitive impairment induced by scopolamine, a muscarinic antagonist, in mice. Pioglitazone (9mg/kg, 18mg/kg) was orally administered for 9 days at 30min before intraperitoneal injection with scopolamine (0.8mg/kg, i.p.). Cognitive function was evaluated by the passive avoidance test and the Morris water maze test on the 10th day after treatment. Changes in cholinergic system reactivity were also examined by measuring the acetylcholine, acetylcholinesterase and choline acetyltransferase in the hippocampus and cortex. Scopolamine injection induced impaired performance in the passive avoidance test and the water maze test and severe decrease of cholinergic system reactivity, as indicated by reduced acetylcholine levels, decreased choline acetyltransferase activity and increased acetylcholinesterase activity. Daily administration of pioglitazone significantly increased step-through latency in passive avoidance test, and significantly decreased the escape latency, and increased the time spent in the platform quadrant in the Morris water maze test. Pioglitazone also protected against scopolamine-induced cholinergic system deficit, including reduced acetylcholine levels, decreased choline acetyltransferase activity and increased acetylcholinesterase activity in the hippocampus or cortex. Pioglitazone demonstrates a significant neuroprotective effect against scopolamine-induced cholinergic system deficit and cognitive impairment.

GW1929: A nonthiazolidinedione PPARγ agonist, ameliorates neurological damage in global cerebral ischemic-reperfusion injury through reduction in inflammation and DNA fragmentation

Transient global cerebral ischemia results in acute neurodegeneration in selective brain areas. Global cerebral ischemic-reperfusion (IR) injury induced selective hippocampal damage results into various neurobehavioral deficits including spatial memory and learning deficiencies. In this study, we have investigated the protective effects of a nonthiazolidinedione PPARγ agonist, N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino)ethyl]- l-tyrosine (GW1929), against global cerebral IR injury induced neurobehavioral deficits and brain damage in gerbils. Bilateral carotid artery occlusion induced global cerebral ischemia in gerbils resulted in neurological deficits, hyperlocomotion, reduced response latency in passive avoidance test and hippocampal damage. Hippocampal neurodegeneration after cerebral IR injury was also associated with significant increase in iNOS and MMP-9 immunoreactivity along with TNFα and IL-6 levels. Massive apoptotic DNA fragmentation as evident from increased TUNEL (terminal deoxynucleotidyl transferase mediated dUTP nick end labelling)-positive cells was also observed in the CA1 hippocampal region of IR challenged gerbils. GW1929 treatment significantly ameliorated cerebral IR induced neurological symptoms, hyperlocomotion, cognitive deficits and hippocampal neuronal damage in CA1 hippocampus region in gerbils. Significant reduction in IR injury induced iNOS and MMP-9 immunoreactivity, TNFα and IL-6 levels and apoptotic DNA fragmentation was also observed with GW1929 treatment. Pioglitazone, thiazolidinedione PPARγ agonist also exhibited similar effects on inflammatory parameters after global cerebral IR injury. In summary, this study demonstrates neuroprotective effects of GW1929 in global cerebral IR injury induced neurobehavioral deficits and brain pathology which may be attributed to reduced inflammation and apoptotic DNA fragmentation, suggesting therapeutic potential of PPARγ agonists in cerebral IR injury.