Lipopolysaccharide-induced Memory Impairment Research Articles

Effect of simultaneous application of adenosine A1 receptor agonist and A2A receptor antagonist on memory, inflammatory factors, and PSD-95 in lipopolysaccharide-induced memory impairment

The potential role of adenosine, a natural neuroprotective agent, and its receptors in the pathogenesis of Alzheimer's disease has been proposed. The present study aims to examine the effect of administering both an A1 receptor agonist and an A2A adenosine receptor antagonist simultaneously on memory, inflammatory factors, and PSD-95 in an LPS-induced Alzheimer's disease model in rats. Fifty-six male Wistar rats were randomly divided into seven groups: Saline, LPS, Saline + Vehicle, LPS + Vehicle, LPS + SCH58261 (A2A receptor antagonist), LPS + CPA (A1 receptor agonist), LPS + SCH58261+CPA. LPS (3 mg/kg/ip) was used to cause memory impairment. Treatment was performed by intraventricular injection of CPA at a dose of 700 μg and SCH-58261 at 40 μg for ten days. Passive avoidance and Y-maze tests were performed to examine animals’ memories. IL-10, TNF-α, and PSD-95 levels were measured in the brain using ELISA and western blot, respectively. Compared to the groups receiving each medication separately, the simultaneous administration of CPA and SCH58261 improved memory (P<0.05). Additionally, compared to the single medication groups, there was a significant increase in IL-10, PSD-95, and a significant decrease in TNF-α in the brain tissue (P<0.05). These findings suggest that the activation of A1 receptors along with A2A receptor inhibition could be a potential therapeutic strategy for Alzheimer's disease. These findings suggest that A1 receptor activation combined with A2A receptor inhibition may be a promising therapeutic approach for Alzheimer's disease.

Pomegranate polyphenol punicalin ameliorates lipopolysaccharide-induced memory impairment, behavioral disorders, oxidative stress, and neuroinflammation via inhibition of TLR4-NF-кB pathway.

Neuroinflammation may play an important role in the development of Alzheimer's disease (AD). Previous studies have reported that lipopolysaccharide (LPS)-induced neuroinflammation causes memory impairments and behavioral disorders. We investigated the potential preventive effects of punicalin (PUN), a polyphenolic component of pomegranate, on LPS-induced memory deficiency and anxiety- and depression-like behaviors, along with the underlying mechanisms. LPS-treated cultured microglial BV2 cells and BV2 cell/Neuro-2a (N2a) cell coculture system were investigated for anti-neuroinflammatory effects of PUN in vitro. The in vivo experiments involved mice administered a 4-week course of oral gavage with 1500 mg/kg/d PUN before intraperitoneal LPS (250 mg/kg daily 7 times) injections. The in vitro results demonstrated that PUN inhibited the LPS-induced inflammatory cytokine (IL-18, IL-1β, TNF-ɑ, and IL-6) production in BV2 cells and protected N2a cells from synaptic damage mediated by BV2 microglia-induced neuroinflammation. In in vivo studies, it was observed that PUN improved memory impairment and anxiety- and depression-like behaviors caused by LPS and reduced the expression of inflammatory proteins such as iNOS, COX-2, IL-1β, IL-2, IL-6, and TNF-α. Furthermore, PUN inhibited the LPS-induced production of MDA; increased the activities of CAT, SOD, and GSH-Px, and inhibited LPS-induced Aβ1-42 generation through down-regulation of APP and BACE1 expression. Moreover, PUN also suppressed the expression of TLR4, IRAK4, TRAF6, IKK-β, NF-κB, p65, and HMGB1 in LPS-treated mouse brain and cultured microglial BV-2 cells. These results suggest that PUN inhibits LPS-induced memory impairment via anti-inflammatory and anti-amylogenic mechanisms through inhibition of TLR4-NF-kB activation.

Isoamericanin A improves lipopolysaccharide-induced memory impairment in mice through suppression of the nicotinamide adenine dinucleotide phosphateoxidase-dependent nuclear factor kappa B signaling pathway.

Alzheimer's disease (AD) is the most frequent cause of dementia in the elderly. Isoamericanin A (ISOA) is a natural lignan possessing great potential for AD treatment. This study investigated the efficacy of ISOA on memory impairments in the mice intrahippocampal injected with lipopolysaccharide (LPS) and the underlying mechanism. Y-maze and Morris Water Maze data suggested that ISOA (5 and 10 mg/kg) ameliorated short- and long-term memory impairments, and attenuated neuronal loss and lactate dehydrogenase activity. ISOA exerted anti-inflammatory effect demonstrating by the reduction of ionized calcium-binding adapter molecule 1 positive cells and suppression of marker protein and pro-inflammation cytokines expressions induced by LPS. ISOA suppressed the nuclear factor kappa B (NF-κB) signaling pathway by inhibiting IκBα phosphorylation and NF-κB p65 phosphorylation and nuclear translocation. ISOA inhibited superoxide and intracellular reactive oxygen species accumulation by reducing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, demonstrating by suppressing NADP+ and NADPH contents, gp91phox expression, and p47phox expression and membrane translocation. These effects were enhanced in combination with NADPH oxidase inhibitor apocynin. The neuroprotective effect of ISOA was further proved in the in vitro models. Overall, our data revealed a novel pharmacological activity of ISOA: ameliorating memory impairment in AD via inhibiting neuroinflammation.

Nigella sativa seeds oil alleviates lipopolysaccharide-induced memory impairment

Nigella sativa seeds oil alleviates lipopolysaccharide-induced memory impairment

P.0543 Catechol-o-methyltransferase inhibitor tolcapone alleviates lipopolysaccharide induced memory impairment

P.0543 Catechol-o-methyltransferase inhibitor tolcapone alleviates lipopolysaccharide induced memory impairment

Rosinidin Attenuates Lipopolysaccharide-Induced Memory Impairment in Rats: Possible Mechanisms of Action Include Antioxidant and Anti-Inflammatory Effects.

The investigation aimed to evaluate the favourable effects of rosinidin in lipopolysaccharide (LPS)-induced learning and memory impairment in rats. Adult Wistar rats (150–200 g) were segregated equally into four different groups and treated as below: Group 1 (normal) and Group 2 (LPS control) were administered orally with 3 mL of 0.5% SCMC (vehicle); Group 3 and Group 4 were test groups and orally administered with rosinidin lower dose (10 mg/kg) and higher dose 20 mg/kg. Daily, 1 h post-offer mentioned treatments, Group 1 animals were injected with normal saline (i.p.) and groups 2–4 were treated with 1 mg/kg/day of LPS. This treatment schedule was followed daily for 7 days. During the treatment, schedule rats were evaluated for spontaneous locomotor activity, memory, and learning abilities. The biochemical assessment was carried out of acetylcholine esterase (AChE), endogenous antioxidants (GSH, SOD, GPx, and catalase), oxidative stress marker MDA, neuroinflammatory markers (IL-6, IL-1β, TNF-α, and NF-κB), and BDNF. LPS-induced reduced spontaneous locomotor activity and memory impairment in the animals. Moreover, LPS reduced GSH, SOD, GPx, and catalase levels; altered activities of AChE; elevated levels of MDA, IL-6, IL-1β, TNF-α, and NF-κB; and attenuated the levels of BDNF in brain tissue. Administration of rosinidin to LPS-treated animals significantly reduced LPS-induced neurobehavioral impairments, oxidative stress, neuroinflammatory markers, and reversed the Ach enzyme activities and BDNF levels towards normal. Results demonstrated that rosinidin attenuates the effects of LPS on learning memory in rats.

Amelioration of lipopolysaccharide-induced memory impairment in equilibrative nucleoside transporter-2 knockout mice is accompanied by the changes in glutamatergic pathways

Neuroinflammation has been implicated in cognitive deficits in neurological and neurodegenerative diseases. Lipopolysaccharide (LPS)-induced neuroinflammation and the breakdown of the blood–brain barrier can be attenuated in mice with equilibrative nucleoside transporter-2 (ENT2/Ent2) deletion. The present study was aimed to investigate the role of ENT2 in cognitive and neuronal functions under physiological and inflammatory conditions, in terms of behavioral performance and synaptic plasticity in saline- and LPS-treated Ent2 knockout (KO) mice and their wild-type (WT) littermate controls. Repeated administrations of LPS significantly impaired spatial memory formation in Morris water maze and hippocampal-dependent long-term potentiation (LTP) in WT mice. The LPS-treated WT mice exhibited significant synaptic and neuronal damage in the hippocampus. Notably, the LPS-induced impairment in spatial memory and LTP performance were attenuated in Ent2 KO mice, along with the preservation of neuronal survival. The beneficial effects were accompanied by the normalization of excessive extracellular glutamate and aberrant downstream signaling of glutamate receptor activation, including the upregulation of phosphorylated p38 mitogen-activated protein kinase and the downregulation of phosphorylated cyclic adenosine monophosphate-response element-binding protein. There was no significant difference in behavioral outcome and all tested parameters between these two genotypes under physiological condition. These results suggest that ENT2 plays an important role in regulating inflammation-associated cognitive decline and neuronal damage.

Hydrogen Sulfide Ameliorates Lipopolysaccharide-Induced Memory Impairment in Mice by Reducing Apoptosis, Oxidative, and Inflammatory Effects.

Hydrogen sulfide (H2S) is reported to have a neuroprotective activity; however, the role of H2S in neuroinflammation-induced neuronal damage is ambiguous. Here, we aimed to evaluate the underlying mechanisms for the neuroprotective effect of NaHS, a known H2S donor, against lipopolysaccharide (LPS)-induced memory impairment (MI). All the treatments were administered for 28days, and LPS (0.25mg/kg i.p.) was co-administered intermittently for 7days from days 15 to 21. Morris water maze (MWM) and Y-maze tests were performed to evaluate MI. Neurodegeneration was histopathologically examined, and the brain homogenates were characterized for reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor (TNF)-α, interleukin (IL)-6, caspase-3, c-Jun, and acetylcholinesterase (AChE) by biochemical analysis. H2S administration significantly improved spatial and working memory in MWM and Y-maze tasks, respectively. Exogenous H2S significantly reversed LPS-induced oxidative stress as evidenced by improved GSH, MDA, and SOD levels. H2S pretreatment significantly attenuated LPS-induced apoptosis and inflammation by decreasing c-Jun and caspase-3 levels and inhibiting TNF-α and IL-6, respectively. The decrease in these markers was supported by H&E and Nissl staining, which confirmed the anti-necrotic activity of H2S. However, there was no significant improvement in LPS-induced increase in AChE activity. These results indicate that chronic systemic inflammation leads to neurodegeneration and MI and H2S exerts its neuroprotective effect due to its anti-oxidative, anti-inflammatory, and anti-apoptotic potential via modulation of JNK and extrinsic apoptosis pathways.

P.075 Cholecalciferol improves memory in rats with lipopolysaccharide-induced memory impairment

The article presents a proposal to use basalt fibers recovered from damaged basalt rods. The introductory part reveals state of the art review on application of various fibers to improve mechanical properties of concrete composites. Authors refer to applications of steel, polypropylene, glass and carbon fibers, their advantages and limitations. Basalt fibers are presented as an alternative solution. Preparation of basalt fiber – concrete composite samples and methodology of their testing is described and illustrated in following section. Results of compressive capacity and stiffness of are given with regard to the basalt fibers amount in the composite. Short discussion and final conclusions are given supporting the idea of basalt fiber spread reinforcement of concrete composites.

Amelioration of oxidative stress and neuroinflammation in lipopolysaccharide-induced memory impairment using Rosmarinic acid in mice.

Oxidative stress plays a pivotal part in the manifestation of neuroinflammation, which further leads to neurodegenerative diseases like Alzheimer's disease (AD). Systemic administration of lipopolysaccharide (LPS) induces neuroinflammation resulting in memory impairment (MI) and cognitive decline. In this study, we evaluated whether prophylactic administration of Rosmarinic acid (RA), a naturally occurring compound, exerts a neuroprotective effect in LPS-induced MI and cognitive decline. Herein, Swiss albino mice were pre-treated with RA (0.5mg/kg and 1mg/kg i.p.) for 28 days and were intermittently exposed to LPS (0.25mg/kgi.p.) for 7 days. LPS caused poor memory retention and increased cognitive decline in Morris water maze (MWM) and Y maze paradigms respectively. Additionally, LPS increased oxidative stress which was denoted by a decrease in superoxide dismutase (SOD) activity, decrease in reduced glutathione (GSH) levels, and increased lipid peroxidation in the brain. Imbalance in the cholinergic system was analyzed by measuring the acetylcholinesterase (AChE) activity. Pre-treatment with RA improved memory and behavioral disturbances by alleviating oxidative stress and AChE activity. LPS augmented levels of tumor necrosis factor (TNF-α), interleukin (IL)-6, caspase-3, and c-Jun. Pre-treatment with RA revitalized the elevated levels of proinflammatory cytokines and apoptotic proteins. In conclusion, this study showcases the amelioration of MI by RA in LPS-challenged memory and cognitive decline, which could be credited to its anti-oxidant effect, inhibitory effect on both proinflammatory cytokines and apoptotic regulators, and reduction in AChE activity.

Chrysophyllum albidum (African star apple) fruit-supplemented diet enhances cognitive functions and attenuates lipopolysaccharide-induced memory impairment, oxidative stress, and release of proinflammatory cytokines.

PurposeFruit-based supplement has an important role in protecting the brain against oxido-inflammatory stress. Chrysophyllum albidum fruit contained several phytonutrients that possess antioxidants and anti-inflammatory properties. Hence, this study investigated the effect of C. albidum fruit supplemented diet (CAFD) on cognitive functions and lipopolysaccharide (LPS)-induced memory impairment and oxido-inflammatory response in mice.MethodsMice were randomized into two experiments. Experiment 1 with naïve mice contained four groups (n = 6) while experiment 2 with LPS contains five groups (n = 6). Mice in experiments 1 and 2 were fed on CAFD (5%, 10%, and 20%) in naïve (6 weeks) and LPS (250 μg/kg, i.p.) in the 7th week, respectively. Cognitive performance was tested using Y-maze test (YMT) and novel object recognition test (NORT) in the naïve and LPS mice. Brain samples were obtained for determination of oxido-inflammatory parameters and acetylcholinesterase activity.ResultsThe CAFD significantly enhanced cognitive performance in the YMT and NORT in naïve and LPS mice, as evidenced by increased % alternation and discrimination index, respectively. CAFD supplementation significantly reduced acetylcholinesterase enzyme activity while it attenuated depletion of reduced glutathione and catalase activities in brains of naive and LPS-treated animals. The CAFD significantly reduced LPS-induced increased malondialdehyde levels in mice brains. CAFD supplementation significantly attenuated LPS-induced pro-inflammatory cytokines (IL-6, TNF-α) in mice brains.ConclusionChrysophyllum albidum fruit supplementation in diet enhances memory function and prevents cognitive deficits induced by LPS via mechanisms associated with inhibition of oxidative stress-related processes, acetylcholinesterase activity, and pro-inflammatory mediators.

Inhibitory effect of carvacrol on lipopolysaccharide-induced memory impairment in rats.

Neuroinflammation is an important process underlying a wide variety of neurodegenerative diseases. Carvacrol (CAR) is a phenolic monoterpene commonly used as a food additive due to its antibacterial properties, but it has also been shown to exhibit strong antioxidative, anti-inflammatory, and neuroprotective effects. Here, we sought to investigate the effects of CAR on inflammation in the hippocampus and prefrontal cortex, as well as the molecular mechanisms underlying these effects. In our study, lipopolysaccharide was injected into the lateral ventricle of rats to induce memory impairment and neuroinflammation. Daily administration of CAR (25, 50, and 100 mg/kg) for 21 days improved recognition, discrimination, and memory impairments relative to untreated controls. CAR administration significantly attenuated expression of several inflammatory factors in the brain, including interleukin-1β, tumor necrosis factor-α, and cyclooxygenase-2. In addition, CAR significantly increased expression of brain-derived neurotrophic factor (BDNF) mRNA, and decreased expression of Toll-like receptor 4 (TLR4) mRNA. Taken together, these results show that CAR can improve memory impairment caused by neuroinflammation. This cognitive enhancement is due to the anti-inflammatory effects of CAR medicated by its regulation of BDNF and TLR4. Thus, CAR has significant potential as an inhibitor of memory degeneration in neurodegenerative diseases.

P.411 Investigating the effects of the dopamine receptor agonist pramipexole on learning and memory in rats with lipopolysaccharide-induced memory impairment

P.411 Investigating the effects of the dopamine receptor agonist pramipexole on learning and memory in rats with lipopolysaccharide-induced memory impairment

The possible protective effect of lactoferrin on lipopolysaccharide-induced memory impairment in albino rats

Generally, there are large number of people suffer from cognitive impairment, including impairment of learning, memory and attention.1 However, the exact mechanisms for cognitive dysfunction have r...

Memory enhancing effect of Nigella Sativa hydro-alcoholic extract on lipopolysaccharide-induced memory impairment in rats

In this study, the effects of Nigella Sativa (NS) hydro-alcoholic extract on lipopolysaccharide (LPS)-induced learning and memory impairments, hippocampal cytokine levels, and brain tissues oxidative damage were investigated in rats. The rats were grouped and treated: (1) control (saline), (2) LPS (1 mg/kg i.p.), and (3–5) 100, 200, or 400 mg/kg NS hydro-alcoholic extract 30 min before LPS injection. The treatment was started since 6 days before the behavioral experiments and continued during the behavioral tests (LPS injection 2 h before each behavioral experiment). Finally, the brains were removed for biochemical assessments. In Morris water maze (MWM) test, LPS increased the escape latency and traveled path compared to control group, whereas all doses of NS hydro-alcoholic extract decreased them compared to LPS group. In passive avoidance (PA) test, the latency to enter the dark compartment in LPS group was shorter than control group while in all treated groups it was longer than LPS group. LPS increased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and nitric oxide (NO) metabolites, and decreased thiol content, superoxide dismutase (SOD), and catalase (CAT) in the hippocampal tissues compared to control group while NS hydro-alcoholic extract decreased MDA and NO metabolites and increased thiol content, SOD, and CAT compared to LPS group. Findings of the current study indicated that the hydro-alcoholic extract of NS improved the LPS-induced learning and memory impairments induced by LPS in rats by improving hippocampal cytokine levels and brain tissues oxidative damage.

Individual differences in the brain are associated with resilience versus susceptibility to lipopolysaccharide-induced memory impairment.

Sepsis impairs learning and memory function, yet marked interindividual variability exists in the degree to which sepsis compromises learning and memory function. Thus, testing resilience versus susceptibility to systemic inflammation induced-memory impairment and the underlying mechanism is needed. In the present study, we firstly used lipopolysaccharide (LPS) to induce memory impairment, and then evaluated cognitive function on days 4-7 after the first LPS challenge. Subjects' scores on both behavioral measures were subjected to a hierarchical cluster analysis, identifying two clusters that differed notably on the Y-maze and fear conditioning tests. This analysis divided these subjects into two groups, one cluster (13 of 34 subjects) displayed impaired working and associative memory, named "Susceptive". The remaining cluster (21 of 34 subjects) showed normal memory, named "Resilient". We have also included another group receiving normal saline to serve as the control group. The three groups underwent a battery of biochemical detections. In addition, we investigated whether the individual differences would disappear between the "Resilient" and "Susceptive" groups by using microglia inhibitor minocycline. We showed that as compared with the "Resilient" or control group, the "Susceptive" group was accompanied by increased tumor necrosis factor-alpha, interleukin-1beta (IL-1β), IL-6, and biomarkers of microglia activation ionized calcium binding adaptor molecule-1 and cluster of differentiation 68. Notably, after decreasing the activation of microglia, the differences in cognitive function between the "Resilient" and "Susceptive" groups disappeared. Collectively, our study suggests that individual differences in the brain are associated with resilience versus susceptibility to LPS-induced memory impairment.

Lipopolysaccharide-induced memory impairment in rats: a model of Alzheimer's disease.

Alzheimer's disease (AD) is a primary cause of dementia in the middle-aged and elderly worldwide. Animal models for AD are widely used to study the disease mechanisms as well as to test potential therapeutic agents for disease modification. Among the non-genetically manipulated neuroinflammation models for AD, lipopolysaccharide (LPS)-induced animal model is commonly used. This review paper aims to discuss the possible factors that influence rats' response following LPS injection. Factors such as dose of LPS, route of administration, nature and duration of exposure as well as age and gender of animal used should be taken into account when designing a study using LPS-induced memory impairment as model for AD.

Soyasapogenol B and Genistein Attenuate Lipopolysaccharide-Induced Memory Impairment in Mice by the Modulation of NF-κB-Mediated BDNF Expression.

Lactobacillus plantarum C29-fermented defatted soybean (FDS), which contains soyasaponins such as soyasaponin I (SI) and soyasapogenol B (SB) and isoflavones such as genistin (GE) and genistein (GT), attenuated memory impairment in mice. Moreover, in the preliminary study, FDS and its soyasaponins and isoflavones significantly inhibited NF-κB activation in LPS-stimulated microglial BV2 cells. Therefore, we examined the effects of FDS and its constituents SI, SB, GT, and GE on LPS-induced memory impairment in mice. Oral administration of FDS (80 mg/kg), which has higher concentrations of SB and GE than DS, recovered LPS-impaired cognitive function in Y-maze (55.1 ± 3.5%) and passive avoidance tasks (50.9 ± 19.2 s) to 129.2% (74.1 ± 3.5%) and 114.2% (290.0 ± 22.4 s) of normal mice, respectively (P < 0.05). SB and GE (10 μM) also more potently attenuated LPS-impaired cognitive behavior than SI and GT, respectively. SB (10 mg/kg) was the most effective: treatment recovered LPS-impaired spontaneous alternation and latency time to 105.7% and 126.8% of normal control mice, respectively (P < 0.05). SB and GE significantly increased BDNF expression and CREB phosphorylation in LPS-treated mice and corticosterone-stimulated SH-SY5Y cells. Furthermore, SB and GE (10 μM) also significantly inhibited NF-κB activation in LPS-treated mice. These findings suggested that FDS and its constituent soyasaponins and isoflavones may attenuate memory impairment by the regulation of NF-κB-mediated BDNF expression.

Protective effect against brain tissues oxidative damage as a possible mechanism for beneficial effects of L-arginine on lipopolysaccharide induced memory impairment in rats

L-Arginine (LA) and nitric oxide (NO) have been suggested to have some effects on learning, memory, brain tissues oxidative damage, and neuroinflammation. In this study, protective effect against brain tissues oxidative damage as a possible mechanism for beneficial effects of LA on lipopolysaccharide (LPS) induced memory impairment was investigated. The rats were grouped into and treated by (1) control (saline), (2) LPS (1 mg/kg, IP), (3) LA (200 mg/kg) – LPS (4) LA. In passive avoidance (PA) test, LPS administration shortened the latency to enter the dark compartment in LPS group compared to control (p < .001) which was accompanied with a high level of malondialdehyde (MDA) and NO metabolite concentrations in the hippocampal tissues (p < .001and p < .05, respectively). Pretreatment with LA prolonged the latency in LA-LPS group compared with LPS group (p < .01–.001) and re-stored MDA and NO metabolites in the hippocampal tissues (p < .05). LPS also reduced superoxide dismutase (SOD) and catalase (CAT) activities and thiol content in the hippocampal tissues in LPS group compared to control (p < .05 and p < .001, respectively) which improved by LA when it was administered before LPS in LA-LPS group (p < .05 and p < .001). Finally, the serum TNFα level of LPS group was higher than the control (p < .01) while, in LA-LPS group it was lower than LPS group (p < .01). It seems that the beneficial effects of LA on memory impairment of LPS-treated rats may be due to its protective effects against brain tissues oxidative damage.

Lipopolysaccharide-Induced Memory Impairment in Rats: a Model of Alzheimer's Disease

Lipopolysaccharide-Induced Memory Impairment in Rats: a Model of Alzheimer's Disease