Model Of Memory Impairment Research Articles

Ginsenoside Re Regulates Oxidative Stress through the PI3K/Akt/Nrf2 Signaling Pathway in Mice with Scopolamine-Induced Memory Impairments.

While Ginsenoside Re has been shown to protect the central nervous system, reports of its effects on memory in the model of scopolamine-induced memory impairment are rare. The aim of this study was to investigate the effects of Ginsenoside Re on scopolamine (SCOP)-induced memory damage and the mechanism of action. Male ICR mice were treated with SCOP (3 mg/kg) for 7 days and with or without Ginsenoside Re for 14 days. As evidenced by behavioral studies (escape latency and cross platform position), brain tissue morphology, and oxidative stress indicators after Ginsenoside Re treatment, the memory damage caused by SCOP was significantly ameliorated. Further mechanism research indicated that Ginsenoside Re inhibited cell apoptosis by regulating the PI3K/Akt/Nrf2 pathway, thereby exerting a cognitive impairment improvement effect. This research suggests that Ginsenoside Re could protect against SCOP-induced memory defects possibly through inhibiting oxidative stress and cell apoptosis.

A New Plant Active Polysaccharide from Nicotiana Improves the Lead-Led Impairment of Spatial Memory in Mice by Modulating the Gut Microbiota and IL-6.

Active polysaccharides from plants are broadly applied in the food and health industry. The purpose of this study is to identify a new plant active polysaccharide and to investigate its role in modulating spatial memory. Ultrasonics and DEAE-52 chromatography were used to separate and purify the plant active polysaccharide (PAP). Mice were exposed to 100 ppm of lead acetate from birth to 7 weeks old to establish the memory impairment model. PAPs with concentrations of 200 or 400 ppm were fed to the subject mice each day after weaning in a spatiotemporally separated fashion. At the end of the intervention, mice were examined using the Morris water maze test, microbiome sequencing, cytokine profiling and protein analysis. The derived active polysaccharide was constituted by β-anomeric carbon, indicating a new form of PAP. The PAP significantly ameliorates the memory impairment caused by postnatal lead exposure, as evidenced by the preferred coverage of the test mouse in the hidden platform, demonstrating salient neuroregulatory activity. In terms of the gut microbiome in response to PAP treatment, it was found that the 400 ppm PAP reversed the gut dysbiosis, producing a comparable structure to the intact animals, represented by the relative abundance of Firmicutes and Muribaculum, Desulfovibrio, etc. For cytokines, the PAP reversed the plasma levels of IL-6, suggesting an anti-inflammatory trend in the context of proinflammation caused by lead invasion. By injecting an IL-6 antagonist, Tocilizumab, into the deficient mice, the spatial memory was significantly repaired, which demonstrates the central roles of IL-6 in mediating the positive effect of the PAP. Finally, a histone modification mark, H3K27me3, was found to be potent in responding to the signals conveyed by the PAP. The PAP could improve the memory deficits by remodeling the gut-brain axis centered at the microbiota and IL-6, which is regarded as an important cytokine-modulating brain activity. This is an intriguing instance linking neuromodulation with the active polysaccharide, shedding light on the innovative applications of plant polysaccharides due to the scarcity of similar phenotypic connections.

The role of the cholinergic system in the memory-protecting effects of metformin in a model of scopolamine-induced memory impairment in aged rats

PurposeAs the elderly population grows, the prevalence of dementia is also rapidly increasing worldwide. Metformin, an antidiabetic drug, has been shown to have ameliorative effects on impaired cognitive functions in experimental models. However, studies have generally used young animals. Additionally, although it has a major role in Alzheimer's disease (AD) and memory, literature information about the effects of metformin on the cholinergic system is limited. In this study, we investigated the effects of metformin on memory in a model of scopolamine-induced memory impairment in aged rats. We also examined the effects of metformin on the cholinergic system, which is very important in cognitive functions. MethodsMetformin was administered orally to male Wistar rats (20–22 months old) at 100 mg/kg/day for three weeks. Morris water maze (MWM) tests were performed to assess spatial memory. Before the probe test of the MWM test, scopolamine was injected intraperitoneally at a dose of 1 mg/kg. After testing, animals were sacrificed, whole brains were removed, and hippocampus samples were separated for biochemical analysis. ResultsImpaired memory associated with scopolamine administration was reversed by metformin. In addition, metformin administration ameliorated scopolamine-induced changes in acetylcholine (ACh) levels, acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and choline acetyltransferase (ChAT) activity. ConclusionOur results show that metformin may have protective effects in a scopolamine-induced memory impairment model in aged animals by improving cholinergic function. Metformin shows promise in preventing dementia with its dual cholinesterase inhibition and ChAT activation effect.

Cognition enhancing activity of essential oil of Hedychium coronarium j. Koenig in memory-impaired animal models

Alzheimer's disease (AD) is a degenerative neurological condition that causes loss of memory and cognition. Numerous variables, such as age, environment, lifestyle, and genetics, influence the occurrence of such neurodegenerative diseases. Hedychium coronarium j. Koenig is being used traditionally for various skin problems. In, this study, we evaluated the effect of the anticholinesterase and antioxidant activity of the essential oil of Hedychium coronarium j. Koenig by in vitro as well as in vivo tests in Aluminum chloride (AlCl3) induced zebrafish and mouse models of memory impairment. Hedychium coronarium j. Koenig significantly retained the spatial and fear memory in zebrafish and mice. Oral administration of the essential oil of Hedychium coronarium j. Koenig has neuroprotective effects in the pathogenesis of Alzheimer's disease by regulating lipid peroxidation and reducing oxidative stress in the brains of Aluminum chloride-treated mice and zebrafish, according to biochemical and histopathological studies. These findings suggest that Hedychium coronarium j. Koenig essential oil has anti-amnesic effects via acetylcholine esterase enzyme inhibition and modulation of oxidative stress indicators in neuronal cells. As a result, the current research also suggests that Hedychium coronarium j. Koenig may be used as a natural, complementary therapy for cognitive problems linked to Alzheimer's disease (AD).

Therapeutic potential of Bhiramiyadhi bhavanai choornam in ameliorating scopolamine-induced impaired learning and memory in rats: neuroprotective effects and mechanistic insights

This study intended to explore Bhiramiyadhi bhavanai choornam’s (BBC) effect on scopolamine-induced impaired learning and memory in rats. BBC was prepared and subjected to organoleptic and phytochemical investigations. Scopolamine (2mg/kg, i.p.) was injected into all animals except for the vehicle control group. Donepezil 1mg/kg and BBC (215, 430, and 860mg/kg along with a 1:1 ratio of ghee and honey) were administered orally for 14 days to respective groups. The effect of BBC on locomotor activity, olfactory and spatial memory and exploratory behaviour was evaluated. Later, animals were sacrificed, and brain homogenates were tested for levels of malondialdehyde, antioxidant enzymes, acetylcholinesterase, nitric oxide and TNF-α. A statistical evaluation was carried out. Investigating BBC for phytoconstituents, showed that steroids, phenols, tannins, quinones, alkaloids, flavonoids, glycosides, terpenoids and carbohydrates were present. Treatment with BBC reversed scopolamine-induced learning and memory impairment by significantly (p < 0.001) improving behaviour in the Y maze, novel object recognition test and MWM. BBC also decreased oxidative stress induced by scopolamine by increasing reduced levels of antioxidant enzymes and declining MDA, AChE, NO, and TNF- α levels in the rat brain in a rat model of scopolamine-induced learning and memory impairment.

Amnesiac (AMN) gene and cnc/Nrf2-redox responses in fruit fly model of memory impairment co-administered Solanum leaves and donepezil

BackgroundConsidering that Alzheimer disease (AD) is a disease of multiple etiological theories, there is a continuous quest for multitarget approach for its management. In view of this, combinatory approach using therapeutic drugs and functional foods is gaining wide popularity. Leaves of Solanum spp such as S. nigrum and S. macrocarpon which are cultivated across the world including Southeast Asia and Africa has several health-promoting benefits. While we have previously reported that both S. nigrum and its relative of African origin S. macrocarpon has neuroprotective properties, however, there is dearth of information on their possible interaction with anti-amnesic drugs which suggests a possible novel therapeutic hypothesis. PurposeThis study investigated the effects of combining Black Nightshade (BN; S. nigrum) and African eggplant (AE; S. macrocarpon) dietary inclusions with donepezil, to gain insights into the molecular mechanisms underlying any synergistic effects resulting from the interaction between these food components and the drug, with the ultimate goal of developing comprehensive intervention. MethodsSix to eight-day-old flies were grouped into five. The treatment lasted for seven days and the survival rate of the flies was recorded. Thereafter, acetylcholinesterase (AChE) activity and antioxidant status of the head tissue were assayed. Also, the level of expression of amnesiac gene (AMN) and nuclear factor erythroid 2–related factor 2 (Nrf2) gene, as well as phytochemical present in the samples were quantified. ResultsThe phytochemical screening results revealed abundance of quercetin and kaempferol. Furthermore, the induced group exhibited impaired cholinergic system, increased mortality rate and oxidative stress, as well as reduced catalase activity compared to the control. Treatment with donepezil and the combinations improved flies survival rate and ameliorated the impaired cholinergic system and oxidative stress levels. Similarly, the downregulated expression of AMN and cnc/Nrf2 genes observed in the induced flies was upregulated in the treated groups. The HPLC result revealed the abundance of quercetin in both samples, which could be attributed to their neuroprotective and antioxidant properties. ConclusionsThe administration of donepezil with the consumption of AE but not the combination of donepezil with BN, significantly improved the memory impairment through interactions with the AMN and cnc/Nrf2 genes but not AChE activity.

Scutellaria Baicalensis Georgi Stem and Leaf Flavonoids Ameliorate the Learning and Memory Impairment in Rats Induced by Okadaic Acid.

The objective of this study is to explore the impact and underlying mechanism of Scutellaria baicalensis Georgi stem and leaf flavonoids (SSFs) on cognitive impairment caused by intracerebroventricular injection of okadaic acid (OA) in rats. An experimental model of Alzheimer's disease (AD) was induced in rats by intracerebroventricular injection of OA, resulting in memory impairment. The Morris water maze test was employed to confirm the successful establishment of the memory impairment model. The rats that exhibited significant memory impairment were randomly divided into different groups, including a model group, three SSFs dose groups (25, 50, and 100 mg/kg), and a positive control group treated with Ginkgo biloba tablets (GLT) at a dose of 200 mg/kg. To evaluate the learning and memory abilities of the rats, the Morris water maze test was conducted. Hematoxylin-eosin (HE) staining was used to observe any morphological changes in neurons. Immunohistochemistry (IHC) was performed to measure the expression of choline acetyltransferase (ChAT) protein. Western blotting (WB) was utilized to assess the phosphorylation levels of tau protein at Ser262 and Ser396. The activities of inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (cNOS) were quantified using ultraviolet spectrophotometry. The levels of inflammatory factors, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were measured using ELISA. In rats, the administration of OA via intracerebroventricular injection resulted in cognitive impairment, neuropathological changes, and alterations in protein expression and activity levels. Specifically, the protein expression of ChAT was significantly reduced (P<0.01), while the phosphorylation levels of tau protein at Ser262 and Ser396 were significantly increased (P<0.01). Moreover, iNOS activity in the hippocampus and cerebral cortex exhibited a significant increase (P<0.01), whereas cNOS activity showed a decrease (P<0.05). Furthermore, the levels of IL-1β and TNF-α in the cerebral cortex were elevated (P<0.01), while the level of IL-6 was decreased (P<0.05). The administration of three doses of SSFs and GLT to rats exhibited varying degrees of improvement in the aforementioned pathological alterations induced by OA. SSFs demonstrated the ability to enhance cognitive function and mitigate memory deficits in rats following intracerebroventricular injection of OA. This beneficial effect may be attributed to the modulation of ChAT protein expression, tau hyperphosphorylation, NOS activity, and inflammatory cytokine levels by SSFs.

Treadmill exercise ameliorates chemotherapy-induced memory impairment through Wnt/β-catenin signaling pathway.

Doxorubicin (DOX) is a widely used chemotherapy drug for various cancers and it is known to induce cognitive impairment. The aim of this study was to investigate the effect of treadmill exercise on chemotherapy-induced memory impairment. We assessed whether DOX affects inflammation, mitochondrial Ca2+ retention capacity, and Wnt/β-catenin signaling. Male Sprague-Dawley rats were divided into control group, exercise group, DOX-injection group, and DOX-injection and exercise group. To create a DOX-induced memory impairment model, animals were injected intraperitoneally with DOX (2 mg/kg) dissolved in saline solution once a week for 4 weeks. Treadmill exercise was performed once a day, 5 days a week, for 8 consecutive weeks. Short-term memory was determined using the step-down avoidance test. Western blot was performed for the proinflammatory cytokines, Wnt/β-catenin signaling, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) in the hippocampus. Mitochondrial Ca2+ retention capacity in the hippocampus was also measured. DOX-injection rats showed deterioration of short-term memory along with decreased expression of BDNF and TrkB in the hippocampus. Levels of the proinflammatory cytokines, tumor necrosis factor-α and interleukin-6, were increased in the DOX-injection rats. Wnt/β-catenin signaling was activated and mitochondrial Ca2+ retention capacity was decreased in the DOX-injection rats. However, treadmill exercise alleviated short-term memory impairment, decreased proinflammatory cytokines, increased BDNF and TrkB expression, and enhanced mitochondrial Ca2+ retention capacity. Treadmill exercise restorated Wnt/β-catenin signaling pathway. This study demonstrated that treadmill exercise can be used for patients undergoing chemotherapy with DOX.

Procognitive, Anxiolytic, and Antidepressant-like Properties of Hyperoside and Protocatechuic Acid Corresponding with the Increase in Serum Serotonin Level after Prolonged Treatment in Mice.

Two polyphenols-hyperoside (HYP) and protocatechuic acid (PCA) were reported to exert antidepressant activity in rodents after acute treatment. Our previous study also showed that this activity might have been influenced by the monoaminergic system and the upregulation of the brain-derived neurotropic factor (BDNF) level. A very long-term pharmacological therapy is required for the treatment of a patient with depression. The repetitive use of antidepressants is recognized to impact the brain structures responsible for regulating both emotional and cognitive behaviors. Thus, we investigated the antidepressant, anxiolytic, and procognitive effects of HYP and PCA in mice after acute and prolonged treatment (14 days). Both polyphenols induced an anxiogenic-like effect after acute treatment, whereas an anxiolytic effect occurred after repetitive administration. PCA and HYP showed procognitive effects when they were administered acutely and chronically, but it seems that their influence on long-term memory was stronger than on short-term memory. In addition, the preset study showed that the dose of 7.5 mg/kg of PCA and HYP was effective in counteracting the effects of co-administered scopolamine in the long-term memory impairment model induced by scopolamine. Our experiments revealed the compounds have no affinity for 5-HT1A and 5-HT2A receptors, whereas a significant increase in serum serotonin level after prolonged administration of PCA and HYP at a dose of 3.75 mg/kg was observed. Thus, it supports the involvement of the serotonergic system in the polyphenol mechanisms. These findings led us to hypothesize that the polyphenols isolated from Impatiens glandulifera can hold promise in treating mental disorders with cognitive dysfunction. Consequently, extended studies are necessary to delve into their pharmacological profile.

Capparis sepiaria’s root bark aqueous lyophilisate shows antiamnesic properties on scopolamine induce cognitive impairment in mice

Capparis sepiaria (Capparaceae) is a plant used in African traditional medicine to treat psychiatic disorders. The aim of this study was to assess the anti-amnesic effect of aqueous lyophilisate of the root bark of Capparis sepiaria (C. sepiaria) on scopolamine-induced animal model of memory impairment using Swiss albino adult mice of both sexes. Memory integrity was assessed by Morris water Maze test, Novel Object Recognition (NOR) and Object-location memory (OLT) tasks were used to assess behavioural components of memory processes and learning. Malondialdehyde (MDA), reduced glutathione (GSH), NO levels and catalase were used to assess oxidative stress while acethylcholinesterase activity was used to evaluate acetylcholine activity in the hippocampus tissues. The quantitative phytochemistry and acute toxicity of the roots of C. sepiaria were also evaluated. The aqueous lyophilisate of C. sepiaria at doses of 10 mg/kg and 40 mg/kg significantly increased the discrimination index in the Morris Water Maze and the objet location tasks. The aqueous lyophilisate of C. sepiaria significantly increased hippocampal GSH and catalase levels and decreased hippocampal MDA, NO levels and achetylcholinesterase (AChE) activities. The aqueous lyophilisate of C. sepiaria showed no acute toxicity with a LD50 > 5000 mg/kg, and revealed a content of flavonoids, tannins and phenols. These results suggest that C. sepiaria improve memory impairment induced by scopolamine and therefore possess antiamnesic properties. These properties would result from a modulation of cholinergic neurotransmission as well as an antioxidant activity of the plant.

A Systematic Review of the Role of Gummosin in Improving Memory in the Scopolamine Impaired Memory Model.

In this study, the role of gummosin in improving memory in the scopolamine memory impairment model was systematically examined. Memory and learning are the most developed and complex functions of the nervous system. Learning is the acquisition of new information that occurs as a change in behavior, and memory is the ability to store and retrieve learned information. In other words, memory is a combination of various processes of information acquisition, consolidation, storage and retrieval. The processes of memory consolidation and storage are the result of a series of time-dependent neurobiological events that occur after the initial formation of memory. In addition, this fluctuation of processes related to memory storage can fully occur shortly after the initial learning experience. Memory is a direct result of learning ,as it stores and retrieves learned experiences and information. The results of our study show that scopolamine leads to impaired memory, learning and synaptic plasticity, which is associated with a change in the expression of various genes and a reduction in the number of hippocampal neurons. The disorders that occurred in the rats of the scopolamine group confirm the model used in this study to induce memory and learning deficits, which is consistent with previous studies confirming the model used to induce Alzheimer's disease. The results of the behavioral tests in this study showed that, consistent with previous work, scopolamine caused a significant increase in anxiety behavior that was associated with a decrease in time spent in the central area compared to the control group, while donepezil injection resulted in a decrease in anxiety behavior. The time spent in the central area was increased compared to the scopolamine group.

A Window to the Brain: The Retina to Monitor the Progression and Efficacy of Saffron Repron® Pre-Treatment in an LPS Model of Neuroinflammation and Memory Impairment.

A mechanism shared by most neurodegenerative diseases, like Alzheimer's disease (AD) and Parkinson's disease (PD), is neuroinflammation. It has been shown to have a link between cognitive impairment and retinal function under neuroinflammatory conditions, confirming the essential role of the retina as a window to the brain. Here, we characterize a mouse model of LPS-induced neuroinflammation describing the parallel deterioration of both memory and visual function. Then, we demonstrate, using the Novel Object Recognition test (NOR) and electroretinogram (ERG) recordings, that preventive, chronic treatment with saffron Repron® is able to reduce the neuroinflammation process and prevent the impairment of both cognitive and visual function. The improvement in behavioral and visual function is confirmed by the pattern of expression of neuroinflammation-related genes and related proteins where pre-treatment with Repron® saffron presents a positive modulation compared with that obtained in animals treated with LPS alone. These results hold for retinal tissue and partially in the brain, where it appears that the onset of damage was delayed. This trend underlines the critical role of the retina as a most sensitive portion of the central nervous system to LPS-induced damage and could be used as a "sensor" for the early detection of neurodegenerative diseases such as Alzheimer's.

Suv39h1 Silencing Recovers Memory Decline in Scopolamine-Induced Amnesic Mouse Model.

Histone post-translational modifications play an important role in the regulation of long-term memory and modulation of expression of neuronal immediate early genes (IEGs). The lysine methyltransferase KMT1A/ Suv39h1 (a mammalian ortholog of the Drosophila melanogaster SU (VAR) 3-9) aids in the methylation of histone H3 at lysine 9. We previously reported that age-related memory decline is associated with an increase in Suv39h1 expression in the hippocampus of male mice. The scopolamine-induced amnesic mouse model is a well-known animal model of memory impairment. In the current study, we have made an attempt to find a link between the changes in the H3K9 trimethylation pattern and memory decline during scopolamine-induced amnesia. It was followed by checking the effect of siRNA-mediated silencing of hippocampal Suv39h1 on memory and expression of neuronal IEGs. Scopolamine treatment significantly increased global levels of H3K9me3 and Suv39h1 in the amnesic hippocampus. Suv39h1 silencing in amnesic mice reduced H3K9me3 levels at the neuronal IEGs (Arc and BDNF) promoter, increased the expression of Arc and BDNF in the hippocampus, and improved recognition memory. Thus, these findings suggest that the silencing of Suv39h1 alone or in combination with other epigenetic drugs might be effective for treating memory decline during amnesia.

The Impact of Some Modulators of the Renin-Angiotensin System on the Scopolamine-Induced Memory Loss Mice Model.

As some of the renin-angiotensin-aldosterone system (RAAS)-dependent mechanisms underlying the cognitive performance modulation could include oxidative balance alterations, in this study we aimed to describe some of the potential interactions between RAAS modulators (Losartan and Ramipril) and oxidative stress in a typical model of memory impairment. In this study, 48 white male Swiss mice were divided into six groups and received RAAS modulators (oral administration Ramipril 4 mg/kg, Losartan 20 mg/kg) and a muscarinic receptors inhibitor (intraperitoneal injection scopolamine, 0.5 mg/kg) for 8 consecutive days. Then, 24 h after the last administration, the animals were euthanized and whole blood and brain tissues were collected. Biological samples were then processed, and biochemical analysis was carried out to assess superoxide dismutase and glutathione activities and malondialdehyde concentrations. In the present experimental conditions, we showed that RAAS modulation via the angiotensin-converting enzyme inhibition (Ramipril) and via the angiotensin II receptor blockage (Losartan) chronic treatments could lead to oxidative stress modulation in a non-selective muscarinic receptors blocker (scopolamine) animal model. Our results showed that Losartan could exhibit a significant systemic antioxidant potential partly preventing the negative oxidative effects of scopolamine and a brain antioxidant potential, mainly by inhibiting the oxidative-stress-mediated cellular damage and apoptosis. Ramipril could also minimize the oxidative-mediated damage to the lipid components of brain tissue resulting from scopolamine administration. Both blood serum and brain changes in oxidative stress status were observed following 8-day treatments with Ramipril, Losartan, scopolamine, and combinations. While the serum oxidative stress modulation observed in this study could suggest the potential effect of RAAS modulation and scopolamine administration on the circulatory system, blood vessels endothelia, and arterial tension modulation, the observed brain tissues oxidative stress modulation could lead to important information on the complex interaction between renin-angiotensin and cholinergic systems.

Inhibition of Acetylcholinesterase and Amyloid-β Aggregation by Piceatannol and Analogs: Assessing In Vitro and In Vivo Impact on a Murine Model of Scopolamine-Induced Memory Impairment.

Currently, no drug is effective in delaying the cognitive impairment of Alzheimer's disease, which ranks as one of the top 10 causes of death worldwide. Hydroxylated stilbenes are active compounds that exist in fruit and herbal plants. Piceatannol (PIC) and gnetol (GNT), which have one extra hydroxyl group in comparison to resveratrol (RSV), and rhapontigenin (RHA) and isorhapontigenin (isoRHA), which were metabolized from PIC in vivo and contain the same number of hydroxyl groups as RSV, were evaluated for their effects on Alzheimer's disease-associated factors in vitro and in animal experiments. Among the five hydroxylated stilbenes, PIC was shown to be the most active in DPPH radical scavenging and in inhibitory activities against acetylcholinesterase and amyloid-β peptide aggregations, with concentrations for half-maximal inhibitions of 40.2, 271.74, and 0.48 μM. The different interactions of the five hydroxylated stilbenes with acetylcholinesterase or amyloid-β were obtained by molecular docking. The scopolamine-induced ICR mice fed with PIC (50 mg/kg) showed an improved learning behavior in the passive avoidance tests and had significant differences (p < 0.05) compared with those in the control group. The RHA and isoRHA at 10 μM were proven to stimulate neurite outgrowths in the SH-SY5Y cell models. These results reveal that nutraceuticals or functional foods containing PIC have the potential for use in the treatment of neurodegenerative disorders.

Morus alba fruit diet ameliorates cognitive deficit in mouse model of streptozotocin-induced memory impairment.

Mounting evidence shows that dietary intake of fruits with polyphenols is beneficial to improve impaired memory functions. This study explored the preventive as well as therapeutic effects of diet enriched with Morus alba fruits extract (DEMA) in streptozotocin (STZ) induced mouse model of memory impairment. The study consisted of two facets: one aspect consisted of pretreatment of animals with DEMA for two weeks followed by STZ (i.c.v) intervention and the second phase involved induction of dementia with STZ (i.c.v) followed by treatment with DEMA for 14days. Cognitive functions of animals were measured by Morris Water Maze test and to delineate the associated mechanism of action, brain biochemical estimations (acetyl-cholinesterase activity, myeloperoxidase activity, thiobarbituric acid reactive species, superoxide dismutase activity, reduced glutathione and nitrite/nitrate) and histopathological studies (haematoxylin and eosin staining) were performed. Pre- and post- treatment with DEMA significantly prevented and attenuated, respectively, the detrimental effects of STZ on mice brain. The results demonstrated that dietary modification, by incorporation of M. alba fruits, reduces the incidence and aids in treatment of memory disorder in mice by reducing central cholinergic activity, decreasing oxidative stress and preventing neurodegeneration.

Effects of Nonthermal Radiofrequency Stimulation on Neuronal Activity and Neural Circuit in Mice.

Whether the nonthermal effects of radiofrequency radiation (RFR) exist and how nonthermal RFR acts on the nervous system are unknown. An animal model of spatial memory impairment is established by exposing mice to 2856-MHz RFR in the range of thermal noise (≤1 °C). Glutamate release in the dorsal hippocampus (dHPC) CA1 region is not significantly changed after radiofrequency exposure, whereas dopamine release is reduced. Importantly, RFR enhances glutamatergic CA1 pyramidal neuron calcium activity by nonthermal mechanisms, which recover to the basal level with RFR termination. Furthermore, suppressed dHPC dopamine release induced by radiofrequency exposure is due to decreased density of dopaminergic projections from the locus coeruleus to dHPC, and artificial activation of dopamine axon terminals or D1 receptors in dHPC CA1 improve memory damage in mice exposed to RFR. These findings indicate that nonthermal radiofrequency stimulation modulates ongoing neuronal activity and affects nervous system function at the neural circuit level.

Benzimidazole Derivatives as New Potential NLRP3 Inflammasome Inhibitors That Provide Neuroprotection in a Rodent Model of Neurodegeneration and Memory Impairment [Retraction

[This retracts the article DOI: 10.2147/JIR.S351913.].

Nanoselenium improved learning, memory, and brain-derived neurotrophic factor and attenuated nitric oxide, and oxidative stress in the brain of juvenile hypothyroid rats.

Nanoselenium (Nan S) is a form of selenium element that acts with high absorption and low toxicity. However, few studies have examined the effects of Nan S on cognitive impairment. On the other hand, hypothyroidism is a common disease that causes cognitive disorders. Therefore, this study aimed to investigate the effect of Nan S on memory impairment in rats due to propylthiouracil (PTU) - induced hypothyroidism. The roles of brain-derived neurotrophic factor (BDNF), nitric oxide (NO), and oxidative stress were also challenged. The animals were randomly divided into 4 groups: (1) Control group (normal saline), (2) hypothyroid (Hypo) group: where 0.05% PTU was added to drinking water, (3) and (4) Hypo-Nan S 50, Hypo-Nan S 100 in which 50 or 100µg/ kg of Nan S were injected respectively. After 6 weeks, spatial and avoidance memory was measured by Morris water maze (MWM) and passive avoidance (PA) tests. The animals then underwent deep anesthesia and the serum samples and the hippocampus and cortex were collected to be used for thyroxin and biochemical measurements including malondialdehyde (MDA), NO, thiol, superoxide dismutase (SOD), catalase (CAT), and BDNF. The rats showed an increase in the escape latency and traveled path in MWM in the Hypo group compare with the Control group and these parameters were decreased in both Hypo-Nan S 50 and Hypo-Nan S 100 groups compared to the Hypo group. The rats of both Hypo-Nan S 50 and Hypo-Nan S 100 groups spent longer time and traveled longer distances in the target area during the probe trial of MWM than the Hypo group. In addition, the latency to enter the dark box in the PA test was lower in the Hypo group than in the Control group, which was significantly improved after Nan S treatment. Furthermore, the hippocampal and cortical lipid peroxide marker (MDA) levels and NO metabolites of the Hypo group were significantly increased and the antioxidant markers (total thiol, SOD, and CAT) were significantly inhibited compared to the Control group. Compared with the Hypo group, Nan S administration could significantly decrease the oxidant factors and increase the activities antioxidant system and concentration of BDNF. It is concluded that Nan S might be able to enhance endogenous antioxidant proteins due to its antioxidant activity, thereby improving BDNF and spatial and avoidance memory in the hypothyroidism-induced memory impairment model however, more studies are still necessary to elucidate the exact mechanism(s).

Effect of Noni on Memory Impairment Induced by Hydrocortisone in Mice.

Background Oxidative stress and memory impairment have been implicated as common functional brain diseases. Nuclear factor E2-related factor 2 (Nrf2) is highly induced in oxidative stress, indicating that Nrf2 is an emerging target of memory therapy. This study aimed to investigate the effect of noni on brain memory impairment induced by hydrocortisone and its protective mechanism in mice. Methods Male Kunming mice (n = 8/group) were given hydrocortisone by gastric gavage for 14 consecutive days to establish the memory impairment model, except for those in the control group. On the same day, the corresponding drugs were given by gastric gavage. The changes in ethology were examined. The brains were extracted and subjected to western blot analysis and biochemical analyses to assess the activities of antioxidative stress. Results The middle- and high-dose noni groups exhibited ameliorated ethology, and the high-dose noni group exhibited increased cerebral protein expression of Nrf2, Kelch-like ECH-associated protein 1 (KEAP1), and haem oxygenase-1 (HO-1) compared to the model group. The arrangement of CA3 vertebral cells in the hippocampus of mice was slightly compact, and hyperchromasia and pyknosis were alleviated. Furthermore, biochemical analyses showed that the activities of enzymes related to oxidative stress in the high-dose noni group were increased. Conclusions Noni might be a powerful antioxidant that can protect nerve cells and may possess potential benefits for the treatment of memory impairment.