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Background: Gluta mater gic N-methyl-D-aspartate (NMDA) receptors play vital roles in memory formation. Changes in the activity of these receptors influence memory processes. Ketamine is a noncompetitive NMDA receptor antagonist drug with promising mood-altering and pain-reducing effects in low doses. These effects are believed to be related to altered serotonergic transmission. Methods: The present study investigated the involvement of the serotonergic system in low-dose ketamine administrations' effects on memory acquisition, consolidation, and retrieval processes. Sixty-four male BALB/c mice were used in this experiment and separated into 8t groups. Mice were treated subchronically with a selective serotonin reuptake inhibitor, fluoxetine, and a serotonin depletion agent, p-chlorophenylalanine (pCPA). A serotonin antagonist, methiothepin, and ketamine were acutely administered 60 minutes before or after the behavioral tests. A passive avoidance (PA) test measured emotional memory acquisition, consolidation, and retrieval processes. Hippocampi malondialdehyde (MDA) levels were analyzed, and histopathological examinations were performed. Results: Ketamine alone did not significantly affect memory encoding processes in the PA test, while the ketamine-- fluoxetine combination disrupted memory consolidation. Fluoxetine negatively affected the memory acquisition process, which was normalized during the consolidation and retrieval trials. Drug applications did not significantly alter hippocampal MDA levels. In all ketamine-applied groups, histopathologic alterations were evident. Conclusion: Low-dose ketamine administration induces neurodegeneration, and it also impairs memory functions when combined with fluoxetine, indicating increased serotonergic transmission may be involved in the memory-impairing and neurotoxic effects of ketamine. [ABSTRACT FROM AUTHOR]

The present study focused on examining the impact of vitamin C (Vit C) administration on the function of memory and the status of oxidative stress (OS) in the hippocampal area of the brain using an unpredictable chronic mild stress (UCMS) model in rats. To this end, 50 male Wistar rats (11-12 weeks of age at the start of the study) were assigned to five groups of six animals, including control, UCMS, UCMS + Vit C 50 mg/Kg, UCMS + Vit C 100 mg/Kg, and UCMS + Vit C 400 mg/Kg. The animals received daily intraperitoneal injections of Vit C at a certain time (9 am) before the initiation of a stressor. UCMS, including a progression of typical stressors, was applied for four weeks. Subsequently, using the passive avoidance (PA) and Morris water maze (MWM) tests were performed to investigate learning and memory. Eventually, hippocampal tissues were evaluated in terms of OS criteria. The results revealed that the latency to enter the dark chamber (P < 0. 01 and P < 0.05, PA test) and the time spent in the target quadrant (P < 0.0001, MWM test) were shorter in the UCMS group, while latency to discover the platform was longer (P < 0.05 and P < 0.001, MWM test) compared to the control group. However, UCMS decreased the content of thiol (P < 0.0001), as well as the activities of catalase (P < 0.0001) and superoxide dismutase (P < 0.0001), whereas the concentration of malondialdehyde (P < 0.01) increased in the hippocampal region of the brain in comparison to the control group. Interestingly, Vit C treatment reversed the mentioned effects of UCMS. Therefore, the latency to enter the dark chamber (P < 0. 05 and P < 0.01,1 and 24 h after the shock, PA test, UCMS + Vit C 400) and the time spent in the target quadrant (P < 0. 01 and P < 0.05, MWM test, UCMS + Vit C 400 and UCMS + Vit C 100, respectively) were longer in the UCMS + Vit C groups. Moreover, Vit C increased the content of thiol (P < 0.05, UCMS + Vit C 400), as well as the activity of catalase (P < 0.001, UCMS + Vit C 400) and superoxide dismutase (P < 0.0001, UCMS + Vit C 400, UCMS + Vit C 100), whereas the concentration of malondialdehyde (P < 0. 05 and P < 0.01, UCMS + Vit C 100, UCMS + Vit C 400) decreased in the hippocampal region of the brain in comparison to the UCMS group. Overall, these results suggest that Vit C could reverse UCMS-induced learning and memory impairment possibly through the modulation of brain OS. Key points Memory and learning impairments were induced by unpredictable chronic mild stress (UCMS) Vitamin C could prevent cognitive impairments caused by UCMS in rats by attenuation of oxidative stress in the brain. [ABSTRACT FROM AUTHOR]

In this paper, the seeds and rinds of passion fruit, which are the agricultural waste of juice processing, were recycled to investigate their biological activities for sustainable use. De-oiled seed powders (S) were successively extracted by refluxing 95% ethanol (95E), 50E, and hot water (HW), respectively, to obtain S-95EE, S-50EE, and S-HWE. Dried rind powders were successively extracted by refluxing HW and 95E to obtain rind-HWE and rind-95EE, respectively. S-50EE and S-95EE showed the most potent extracts, such as anti-amyloid-β1-42 aggregations and anti-acetylcholinesterase inhibitors, and they exhibited neuroprotective activities against amyloid-β25-35-treated or H2O2-treated SH-SY5Y cells. Scirpusin B and piceatannol were identified in S-95EE, S-50EE, and rind-HWE, and they showed anti-acetylcholinesterase activity at 50% inhibitory concentrations of 62.9 and 258.9 μM, respectively. Daily pretreatments of de-oiled seed powders and rind-HWE (600 mg/kg), S-95EE, and S-50EE (250 mg/kg) or scirpusin B (40 mg/kg) for 7 days resulted in improved learning behavior in passive avoidance tests and had significant differences (p < 0.05) compared with those of the control in scopolamine-induced ICR mice. The seeds and rinds of passion fruit will be recycled as materials for the development of functional foods, promoting neuroprotection and delaying the onset of cognitive dysfunctions. [ABSTRACT FROM AUTHOR]

Background: The Unani formulation Majun Brahmi (MB), a combination of herbs, is used in India as a brain tonic and memory enhancer. Aluminium deposition in the brain is associated with the development of neurodegenerative diseases. Aims and Objectives: The present study was designed to observe that the effects of MB have been evaluated on aluminium trichloride or aluminium chloride (AlCl3)-induced cognitive impairment in an experimental rat model. Materials and Methods: Twenty male Wistar albino rats were divided into four groups of five rats each. AlCl3 was administered orally for 30 days to induce cognitive impairment. Group I received saline, Group II-AlCl3 (100 mg/kg b.wt), Group III-MB (1027.77 mg/kg b.wt), and Group IV-AlCl3 + MB (100 mg/kg b.wt+1027.77 mg/kg b.wt). At the end of the experiment, rats were subjected to behavioral and biochemical assessments. Results: Animals treated with AlCl3 showed a significant increase in time to reach the platform in the Morris water maze test (MWM), prolonged transfer latency (TL) in the elevated plus maze, and decreased step-down latency in the passive avoidance test, as compared to controls (P

Acid-sensing ion channels (ASICs) are proton-gated ion channels that mediate nociception in the peripheral nervous system and contribute to fear and learning in the central nervous system. Sevanol was reported previously as a naturally-occurring ASIC inhibitor from thyme with favorable analgesic and anti-inflammatory activity. Using electrophysiological methods, we found that in the high micromolar range, the compound effectively inhibited homomeric ASIC1a and, in sub- and low-micromolar ranges, positively modulated the currents of α1β2γ2 GABAA receptors. Next, we tested the compound in anxiety-related behavior models using a targeted delivery into the hippocampus with parallel electroencephalographic measurements. In the open field, 6 µM sevanol reduced both locomotor and θ-rhythmic activity similar to GABA, suggesting a primary action on the GABAergic system. At 300 μM, sevanol markedly suppressed passive avoidance behavior, implying alterations in conditioned fear memory. The observed effects could be linked to distinct mechanisms involving GABAAR and ASIC1a. These results elaborate the preclinical profile of sevanol as a candidate for drug development and support the role of ASIC channels in fear-related functions of the hippocampus. [ABSTRACT FROM AUTHOR]

Background: The Unani formulation Majun Brahmi (MB), a combination of herbs, is used in India as a brain tonic and memory enhancer. Aluminium deposition in the brain is associated with the development of neurodegenerative diseases. Aims and Objectives: The present study was designed to observe that the effects of MB have been evaluated on aluminium trichloride or aluminium chloride (AlCl3)-induced cognitive impairment in an experimental rat model. Materials and Methods: Twenty male Wistar albino rats were divided into four groups of five rats each. AlCl3 was administered orally for 30 days to induce cognitive impairment. Group I received saline, Group II-AlCl3 (100 mg/kg b.wt), Group III-MB (1027.77 mg/kg b.wt), and Group IV-AlCl3 + MB (100 mg/kg b.wt+1027.77 mg/kg b. wt). At the end of the experiment, rats were subjected to behavioral and biochemical assessments. Results: Animals treated with AlCl3 showed a significant increase in time to reach the platform in the Morris water maze test (MWM), prolonged transfer latency (TL) in the elevated plus maze, and decreased step-down latency in the passive avoidance test, as compared to controls (P<0.01). Cotreatment with MB resulted in a reduced time to reach the platform in MWM, increased step-down latencies, and decreased TL. AlCl3 induction significantly increased malondialdehyde and decreased superoxide dismutase, glutathione reductase, glutathione, total antioxidant capacity, and catalase levels. Concomitant administration of MB significantly attenuated the effects AlCl3 on lipid peroxidation and restored the reduced antioxidant parameters. Conclusion: The study provides strong evidence for the potential use of MB in the treatment of neurodegenerative disorders like Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Treating schizophrenia with the available pharmacotherapy is difficult. One possible strategy is focused on the modulation of the function of the endocannabinoid system (ECS). The ECS is comprised of cannabinoid (CB) receptors, endocannabinoids and enzymes responsible for the metabolism of endocannabinoids (fatty acid hydrolase (FAAH) and monoacylglycerol lipase (MAGL)). Here, the aim of the experiments was to evaluate the impact of inhibitors of endocannabinoids' enzymatic degradation in the brain: KML-29 (MAGL inhibitor), JZL-195 (MAGL/FAAH inhibitor) and PF-3845 (FAAH inhibitor), on the memory disturbances typical for schizophrenia in an acute N-methyl-D-aspartate (NMDA) receptor hypofunction animal model of schizophrenia (i.e., injection of MK-801, an NMDA receptor antagonist). The memory-like responses were assessed in the passive avoidance (PA) test. A single administration of KML-29 or PF-3845 had a positive effect on the memory processes, but an acute administration of JZL-195 impaired cognition in mice in the PA test. Additionally, the combined administration of a PA-ineffective dose of KML-29 (5 mg/kg) or PF-3845 (3 mg/kg) attenuated the MK-801-induced cognitive impairment (0.6 mg/kg). Our results suggest that the indirect regulation of endocannabinoids' concentration in the brain through the use of selected inhibitors may positively affect memory disorders, and thus increase the effectiveness of modern pharmacotherapy of schizophrenia. [ABSTRACT FROM AUTHOR]

Serotonin is a neurotransmitter, which is involved in memory via its receptors. The 5-HT1D and 5-HT1F receptors mainly exist in the hippocampus, which plays an important role in memory processing. However, few studies have assessed the effect of these serotonin receptors on memory. We evaluated the effect of a 5-HT1D receptor agonist, PNU142633, 5-HT1D receptor antagonist, BRL15572 hydrochloride, and 5-HT1F receptor agonist, LY344864, on the recognition and avoidance memory in the hippocampus area. Fifty adult male Wistar rats weighing 200–250 g were divided into the control, sham-operated, PNU, BRL, and LY groups (n=10 per group). Bilateral guide cannulas were implanted into the dentate gyrus area of the hippocampus. The drugs were administered at the dose of 1 μg/μl before the novel object recognition (NOR) and passive avoidance learning (PAL) tests. The results showed that in the NOR test, the administration of PNU and LY had no significant effect on recognition index; however, the recognition index was increased by BRL. In the PAL test, the administration of PNU had no significant effect on recognition index, but the administration of BRL and LY increased the time spent in the dark compartment of the apparatus and decreased the step-through latency into the dark compartment apparatus. It can be concluded that the inhibition of the hippocampal 5-HT1D receptor improved cognition memory but impaired avoidance memory. Activation of the hippocampal 5-HT1F receptor had no effect on cognitive memory but impaired avoidance memory. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Pharmacokinetic characteristics as well as cognitive-enhancing nootropic activity of latrepirdine (Dimebon®) in relationship with its polymorphic forms have been studied in SD and Wistar rats. Methods: The pharmacokinetics of six polymorphs (A, B, C, D, E, F) of latrepirdine were studied in male SD rats after 7 days of oral administration in corn oil at a dose of 10 mg/kg once a day. Blood and brain samples were taken on the 7th day of administration at 15 min, 30 min, 60 min and 120 min after administration and analyzed for latrepirdine content by LC-MS. The cognitive-enhancing nootropic effect was studied in male and female Wistar rats after 9 days of oral administration in corn oil at a dose of 10 mg/kg, after prior administration of scopolamine, an agent that causes memory impairment similar to that in Alzheimer's disease. The animals' cognitive function was studied in the passive avoidance test. Results: When studying the pharmacokinetics, the highest bioavailability both in the blood and in the brain was demonstrated by polymorph E, whose AUC was the highest relative to other polymorphs. In the study of the cognitive-enhancing nootropic effect, polymorph E also showed the highest activity, whose values of the latent period of entering the dark chamber did not differ from control animals, and differed from other polymorphs. Conclusion: Thus, the crystal structure has been shown to play a key role in the bioavailability and efficacy of latrepirdine, and polymorph E has also been shown to be a promising drug for the treatment of neurodegenerative diseases associated with memory impairment, such as Alzheimer's disease. [ABSTRACT FROM AUTHOR]

In this paper, the seeds and rinds of passion fruit, which are the agricultural waste of juice processing, were recycled to investigate their biological activities for sustainable use. De-oiled seed powders (S) were successively extracted by refluxing 95% ethanol (95E), 50E, and hot water (HW), respectively, to obtain S-95EE, S-50EE, and S-HWE. Dried rind powders were successively extracted by refluxing HW and 95E to obtain rind-HWE and rind-95EE, respectively. S-50EE and S-95EE showed the most potent extracts, such as anti-amyloid-β1-42 aggregations and anti-acetylcholinesterase inhibitors, and they exhibited neuroprotective activities against amyloid-β25-35-treated or H2O2-treated SH-SY5Y cells. Scirpusin B and piceatannol were identified in S-95EE, S-50EE, and rind-HWE, and they showed anti-acetylcholinesterase activity at 50% inhibitory concentrations of 62.9 and 258.9 μM, respectively. Daily pretreatments of de-oiled seed powders and rind-HWE (600 mg/kg), S-95EE, and S-50EE (250 mg/kg) or scirpusin B (40 mg/kg) for 7 days resulted in improved learning behavior in passive avoidance tests and had significant differences (p < 0.05) compared with those of the control in scopolamine-induced ICR mice. The seeds and rinds of passion fruit will be recycled as materials for the development of functional foods, promoting neuroprotection and delaying the onset of cognitive dysfunctions.

Introduction: Pharmacokinetic characteristics as well as cognitive-enhancing nootropic activity of latrepirdine (Dimebon®) in relationship with its polymorphic forms have been studied in SD and Wistar rats.Methods: The pharmacokinetics of six polymorphs (A, B, C, D, E, F) of latrepirdine were studied in male SD rats after 7 days of oral administration in corn oil at a dose of 10 mg/kg once a day. Blood and brain samples were taken on the 7th day of administration at 15 min, 30 min, 60 min and 120 min after administration and analyzed for latrepirdine content by LC-MS. The cognitive-enhancing nootropic effect was studied in male and female Wistar rats after 9 days of oral administration in corn oil at a dose of 10 mg/kg, after prior administration of scopolamine, an agent that causes memory impairment similar to that in Alzheimer’s disease. The animals’ cognitive function was studied in the passive avoidance test.Results: When studying the pharmacokinetics, the highest bioavailability both in the blood and in the brain was demonstrated by polymorph E, whose AUC was the highest relative to other polymorphs. In the study of the cognitive-enhancing nootropic effect, polymorph E also showed the highest activity, whose values of the latent period of entering the dark chamber did not differ from control animals, and differed from other polymorphs.Conclusion: Thus, the crystal structure has been shown to play a key role in the bioavailability and efficacy of latrepirdine, and polymorph E has also been shown to be a promising drug for the treatment of neurodegenerative diseases associated with memory impairment, such as Alzheimer’s disease.

Acid-sensing ion channels (ASICs) are proton-gated ion channels that mediate nociception in the peripheral nervous system and contribute to fear and learning in the central nervous system. Sevanol was reported previously as a naturally-occurring ASIC inhibitor from thyme with favorable analgesic and anti-inflammatory activity. Using electrophysiological methods, we found that in the high micromolar range, the compound effectively inhibited homomeric ASIC1a and, in sub- and low-micromolar ranges, positively modulated the currents of α1β2γ2 GABAA receptors. Next, we tested the compound in anxiety-related behavior models using a targeted delivery into the hippocampus with parallel electroencephalographic measurements. In the open field, 6 µM sevanol reduced both locomotor and θ-rhythmic activity similar to GABA, suggesting a primary action on the GABAergic system. At 300 μM, sevanol markedly suppressed passive avoidance behavior, implying alterations in conditioned fear memory. The observed effects could be linked to distinct mechanisms involving GABAAR and ASIC1a. These results elaborate the preclinical profile of sevanol as a candidate for drug development and support the role of ASIC channels in fear-related functions of the hippocampus.

Treating schizophrenia with the available pharmacotherapy is difficult. One possible strategy is focused on the modulation of the function of the endocannabinoid system (ECS). The ECS is comprised of cannabinoid (CB) receptors, endocannabinoids and enzymes responsible for the metabolism of endocannabinoids (fatty acid hydrolase (FAAH) and monoacylglycerol lipase (MAGL)). Here, the aim of the experiments was to evaluate the impact of inhibitors of endocannabinoids’ enzymatic degradation in the brain: KML-29 (MAGL inhibitor), JZL-195 (MAGL/FAAH inhibitor) and PF-3845 (FAAH inhibitor), on the memory disturbances typical for schizophrenia in an acute N-methyl-D-aspartate (NMDA) receptor hypofunction animal model of schizophrenia (i.e., injection of MK-801, an NMDA receptor antagonist). The memory-like responses were assessed in the passive avoidance (PA) test. A single administration of KML-29 or PF-3845 had a positive effect on the memory processes, but an acute administration of JZL-195 impaired cognition in mice in the PA test. Additionally, the combined administration of a PA-ineffective dose of KML-29 (5 mg/kg) or PF-3845 (3 mg/kg) attenuated the MK-801-induced cognitive impairment (0.6 mg/kg). Our results suggest that the indirect regulation of endocannabinoids’ concentration in the brain through the use of selected inhibitors may positively affect memory disorders, and thus increase the effectiveness of modern pharmacotherapy of schizophrenia.

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.

Introduction: Pentylenetetrazole (ptz) is a chemical substance that is largely used for the induction of seizure and epilepsy in the animal model, and it can also disrupt 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 rats. Methods: Twenty-four rats were randomly allocated in 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, the rats were anesthetized, their brains were removed, and brain homogenates were prepared; oxidative stress was evaluated using specified methods. Results: Step-through latency according to the passive avoidance test was greater in the bhe receiving group than in the ptz group (p<0.001). In addition, brain lipid peroxidation malondialdehyde (mda) and nitric oxide (no) level in the bhe-treated group was significantly lower (p<0.001), and the reduced glutathione (gsh) levels were significantly greater versus ptz group (p<0.001). Discussion: Our results showed that bhe could prevent memory deficit caused by ptz-induced kindling and this could be attributed to amelioration in oxidative stress damage through antioxidant mechanism. [ABSTRACT FROM AUTHOR]

Background: Dysfunction of the cholinergic system is associated with the development of Alzheimer's disease (AD). One of the new possible strategies for the pharmacological modulation of memory-related problems typical of AD, is connected with the endocannabinoid system (ECS) and the cannabinoid (CB: CB1 and CB2) receptors. Methods: The aim of the study was to determine the influence of the selective CB2 receptor ligands: agonist (JWH 133) and antagonist (AM 630) on different stages of memory and learning in mice, in the context of their interaction with cholinergic pathways. To assess and understand the memory-related effects in mice we used the passive avoidance (PA) test. Results: We revealed that co-administration of non-effective dose of JWH 133 (0.25 mg) or AM 630 (0.25 mg/kg) with the non-effective dose of cholinergic receptor agonist - nicotine (0.05 mg/kg) enhanced cognition in the PA test in mice; however, an acute injection of JWH 133 (0.25 mg/kg) or AM 630 (0.25 mg/kg) had no influence on memory enhancement induced by the effective dose of nicotine (0.1 mg/kg). Co-administration of JWH 133 (0.25 mg) or AM 630 (0.25 mg/kg) with the effective dose of the cholinergic receptor antagonist scopolamine (1 mg/kg) attenuated the scopolamine-induced memory impairment in the PA test in mice. Conclusion: Our experiments have shown that CB2 receptors participate in the modulation of memory-related responses, especially those in which cholinergic pathways are implicated. [ABSTRACT FROM AUTHOR]

Background and Aim: Beta-adrenergic receptors in the basolateral nucleus of the amygdala (BLA) have been associated with stress, learning, and memory. In this study, we tested the effects of intra-BLA microinfusions of the β2-adrenergic receptor agonist, salbutamol, on spatial, passive avoidance memory and long-term potentiation (LTP) in the CA1 region of the hippocampus in response to stress. Materials and Methods: Forty male rats were randomly divided into five groups (n=8/per group): control, sham, stress, salbutamol+control, and salbutamol+stress. Bilateral cannulation was performed in the BLA, by using stereotaxic apparatus. Then, the rats were transferred to the communication box and foot-shock stress induction continued for four consecutive days. Five minutes before stress, salbutamol (4 µl/side) was injected bilaterally into the BLA. Barnes maze and shuttle box were examined for spatial and passive avoidance memory, respectively. The field potential recording was also used to investigate LTP in the CA1 neurons of the hippocampus. Results: The results of the passive avoidance test showed that bilateral injection of salbutamol in the BLA five minutes before stress increased step-through latency time significantly compared to the stress group. Barnes maze results showed that intra-BLA microinfusions of salbutamol before stress, reduced the latency time, the number of errors, and the distance traveling to achieve the target hole compared to the stress group. Field potential recording revealed that salbutamol injection before stress decreased the population spike amplitude significantly and caused fEPSP slope 60 minutes after high-frequency stimulation compared to the stress groups. Conclusion: It seems that the salbutamol in the BLA can improve memory deficits induced by stress.

Cerium oxide nanoparticles (CNPs), owing to their antioxidant property, have recently emerged as therapeutic candidate for Alzheimer's disease (AD). However, intravenous CNPs are limited due to their poor physicochemical properties, rapid blood clearance and poor blood–brain penetration. Thus, we developed intranasal CNPs and evaluated its potential in experimental AD. CNPs were synthesized using homogenous precipitation method and optimized through Box–Behnken Design. The formation of CNPs was confirmed by UV spectroscopy and FTIR. The optimized CNP were spherical, small (134.0 ± 3.35 nm), uniform (PDI, 0.158 ± 0.0019) and stable (ZP, −21.8 ± 4.94 mV). The presence of Ce in CNPs was confirmed by energy-dispersive X-ray analysis. Further, the X-ray diffraction spectra revealed that the CNPs were nano-crystalline. The DPPH assay showed that at concentration of 50 µg/mL, the percentage radical scavenging was 95.40 ± 0.006%. Results of the in vivo behavioral studies in the scopolamine-induced Alzheimer rat model showed that intranasal CNPs dose dependently reversed cognitive ability. At dose of 6 mg/kg the morris water maze results (escape latency, path length and dwell time) and passive avoidance results (retention latency) were significantly different from untreated group but not significantly different from positive control group (rivastigmine patch, 13.3 mg/24 h). Further, biochemical estimation showed that intranasal CNP upregulated the levels of SOD and GSH in brain. In conclusion, intranasal CNPs, through its antioxidant effect, could be a prospective therapeutics for the treatment of cognitive impairment in AD. [ABSTRACT FROM AUTHOR]

There is substantial evidence that anti-inflammatory agents and antioxidants have neuroprotective properties and may be useful in the treatment of neurodegenerative disorders. In this regard, the effects of oxaprozin (OXP) (a nonsteroidal anti-inflammatory drug) on the experimental model of seizure and memory impairment caused by seizures in rats were investigated in the present study. Seizures in male Wistar rats (200–250 g, 8 weeks) were induced by pentylenetetrazol (PTZ, 60 mg/kg). The anticonvulsant effects of OXP (100, 200, and 400 mg/kg, administered intraperitoneally) were evaluated in the seizure model. The effect on memory was assessed using the passive avoidance (PA) test. After behavioral tests, the animals underwent deep anesthesia and were euthanized painlessly. Animal serum was isolated for antioxidant assays (MDA and GPx). The animals' brains (hippocampus) were also isolated to gauge the relative expression of genes in the oxidative stress pathway (Nrf2/HO-1). Intraperitoneal injection of OXP decreased the mean score on the Racine scale compared to the PTZ group. Moreover, in the PA test, OXP caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that OXP was able to significantly increase GPx serum levels and significantly reduce MDA serum levels compared to the PTZ group. Quantitative polymerase chain reaction (qPCR) results also revealed that OXP counteracted the negative effects of PTZ by significantly increasing the expression of the Nrf2 and Hmox1 genes. Overall, this study suggests the potential neuroprotective effects of the nonsteroidal anti-inflammatory drug OXP in a model of memory impairment caused by seizures via inhibition of the oxidative stress pathway. [ABSTRACT FROM AUTHOR]

Cognitive impairment is a serious side effect of post-myocardial infarction (MI) course. We have recently demonstrated that human adipose-derived stem cells (hADSCs) ameliorated myocardial injury after MI by attenuating reactive oxygen species (ROS) levels. Here, we studied whether the beneficial effects of intramyocardial hADSC transplantation can extend to the brain and how they may attenuate cognitive dysfunction via modulating ROS after MI. After coronary ligation, male Wistar rats were randomized via an intramyocardial route to receive either vehicle, hADSC transplantation (1 × 106 cells), or the combination of hADSCs and 3-Morpholinosydnonimine (SIN-1, a peroxynitrite donor). Whether hADSCs migrated into the hippocampus was assessed by using human-specific primers in qPCR reactions. Passive avoidance test was used to assess cognitive performance. Postinfarction was associated with increased oxidative stress in the myocardium, circulation, and hippocampus. This was coupled with decreased numbers of dendritic spines as well as a significant downregulation of synaptic plasticity consisting of synaptophysin and PSD95. Step-through latency during passive avoidance test was impaired in vehicle-treated rats after MI. Intramyocardial hADSC injection exerted therapeutic benefits in improving cardiac function and cognitive impairment. None of hADSCs was detected in rat's hippocampus at the 3rd day after intramyocardial injection. The beneficial effects of hADSCs on MI-induced histological and cognitive changes were abolished after adding SIN-1. MI-induced ROS attacked the hippocampus to induce neurodegeneration, resulting in cognitive deficit. The remotely intramyocardial administration of hADSCs has the capacity of improved synaptic neuroplasticity in the hippocampus mediated by ROS, not the cell engraftment, after MI. Key messages: Human adipose-derived stem cells (hADSCs) ameliorated injury after myocardial infarction by attenuating reactive oxygen species (ROS) levels. Intramyocardial administration of hADSCs remotely exerted therapeutic benefits in improving cognitive impairment after myocardial infarction. The improved synaptic neuroplasticity in the hippocampus was mediated by hADSC-inhibiting ROS, not by the stem cell engraftment. [ABSTRACT FROM AUTHOR]

Abstract Brain Factor-7® (BF-7), silk fibroin peptide, is known to be effective in improvement of memory and learning ability. In this study, the effects of BF-7 (10 mg/kg, p.o., pre-treatment for 7 days and post-treatment for 7 days) on neuroprotection and memory and learning functions were investigated in a rat model of transient focal cerebral ischemia and a gerbil model of transient global forebrain ischemia. Furthermore, to find the mechanism of BF-7, we examined the neuroprotective and antioxidative effects of BF-7 in vitro using neuroblastoma (SH-SY5Y) cells. In vivo model, treatment with BF-7 significantly reduced the number of errors in 8-arm maze test and significantly increased latency time in passive avoidance test at 7 days after focal ischemia compared to those in the vehicle-treated group. In addition, treatment with BF-7 significantly decreased the infarct size or neuronal death at 7 day following transient ischemia compared to that in the vehicle-treated group. In vitro model, 10 or 20 μg/ml of BF-7 treatment significantly increased cell viability in dose-dependent manner. In addition, oxidative stress was significantly attenuated in the ischemic cells, showing that 10 or 20 μg/ml of BF-7 treatment significantly reduced the generation of reactive oxygen species (ROS) compared to that in the ischemic cells. These results indicate that BF-7 treatment can attenuate ischemic damages and improve memory deficits via reduction of ROS generation.

Background Bile duct ligation (BDL) has been used for experimental research on hepatic encephalopathy (HE) caused by chronic liver disease. However, little research has been done on a BDL model in C57BL/6 mouse. Therefore, we evaluated the suitability of a BDL model in C57BL/6 mouse for the study of HE and determined which behavioral tests are appropriate for the identification of HE in this model. Methods Twelve to fourteen-week-old male C57BL/6 mice were randomly assigned to either sham group or BDL group. Histological changes in liver were confirmed by hematoxylin/eosin and Masson’s trichrome staining. Liver function alterations were detected by alanine aminotransferase (ALT) and ammonia levels. To identify behavioral changes, open field, elevated plus maze, novel object recognition, and passive avoidance tests were performed. Results Inflammatory liver injury and fibrosis were observed 14 days after BDL. ALT and ammonia levels were significantly higher in BDL group than in sham group. There were no differences in general locomotor activity or anxiety between the groups. No difference was observed between these two groups in the novel object recognition test, but BDL group showed significant learning/memory impairment in the passive avoidance test compared to sham group. Conclusions Fourteen days of BDL in 12–14-week-old male C57BL/6 mice is a clinically relevant model for HE, as these mice have liver fibrosis with impaired liver function, hyperammonemia, and learning/memory impairment. Passive avoidance can be used as the major behavioral test in this model of HE.

Citral, a common monoterpene found in numerous plants, is an interesting compound that has been shown to have various biological activities. Although it is widely distributed in nature and there are many studies presenting its biological activities, its anti-neurodegenerative activity, especially under in vivo conditions, is very poorly understood. Thus, this paper aimed to deepen knowledge about citral activity towards factors and symptoms of neurodegeneration. To accomplish this, several comprehensive tests were conducted, including the estimation of butyrylcholinesterase inhibition, the evaluation of hepatotoxicity and the detection of oxidative stress and lipid peroxidation in vitro, as well as an in vivo behavioral assessment using mice models. Additionally, ex vivo determination of level of the compound in the brain and blood of a tested animal was undertaken. The results obtained revealed that citral is able to inhibit butyrylcholinesterase activity and protect hepatic cells against oxidative stress and lipid peroxidation in vitro. Moreover, behavioral tests in vivo indicated that citral (50 mg/kg) improves memory processes associated with acquisition (passive avoidance test), both in acute and subchronic administration. Additionally, we found that the administration of citral at 25 mg/kg and 50 mg/kg did not significantly affect the locomotor activity. Beyond the aforementioned, gas chromatography-mass spectrometry analysis revealed the presence of the compound in the blood and brain after subchronic administration of citral. Taken together, the results obtained in vitro, in vivo and ex vivo clearly indicate that citral is a promising monoterpene that can potentially be used towards cognition improvement.

Objective: Zataria multiflora (Zm) has been proposed for memory enhancing in Persian traditional medicine; but to now, no study has been carried out in this field yet. The aim of this research was to study the plant effect on spatial memory in scopolamine-induced amnesia and investigate in vivo anticholinesterase effect of Zm. Material and Methods: Aerial parts of the plant were extracted with methanol and standardized on the basis of rutin content. Male rats received three doses of Zm extract (100, 200 and 400 mg/kg, intraperitoneal (ip) for 7 days) and 30 min after the latest dose, scopolamine (1 mg/kg) was administered to animals. Learning capacity and spatial memory were studied using morris water maze (MWM) and passive avoidance test (PAT) methods. Anticholinesterase activity was studied using Ellman’s method. Physostigmine (0.3 mg/kg) and piracetam (200 mg/kg) were used as positive controls. Results: All doses of Zm extract significantly decreased the distance and time spent to find the platform in MWM and increased the time latency in PAT test. In both MWM and PAT tests, the highest effect of Zm was observed at 200 mg/kg which was in accordance with AChE inhibitory effect of the plant. Conclusion: Our findings indicate that Zm has anti-amnesic effect and might improve memory deficit through anticholinesterase activity.

Background: Dysfunction of the cholinergic system is associated with the development of Alzheimer’s disease (AD). One of the new possible strategies for the pharmacological modulation of memory-related problems typical of AD, is connected with the endocannabinoid system (ECS) and the cannabinoid (CB: CB1 and CB2) receptors. Methods: The aim of the study was to determine the influence of the selective CB2 receptor ligands: agonist (JWH 133) and antagonist (AM 630) on different stages of memory and learning in mice, in the context of their interaction with cholinergic pathways. To assess and understand the memory-related effects in mice we used the passive avoidance (PA) test. Results: We revealed that co-administration of non-effective dose of JWH 133 (0.25 mg) or AM 630 (0.25 mg/kg) with the non-effective dose of cholinergic receptor agonist - nicotine (0.05 mg/kg) enhanced cognition in the PA test in mice; however, an acute injection of JWH 133 (0.25 mg/kg) or AM 630 (0.25 mg/kg) had no influence on memory enhancement induced by the effective dose of nicotine (0.1 mg/kg). Co-administration of JWH 133 (0.25 mg) or AM 630 (0.25 mg/kg) with the effective dose of the cholinergic receptor antagonist scopolamine (1 mg/kg) attenuated the scopolamine-induced memory impairment in the PA test in mice. Conclusion: Our experiments have shown that CB2 receptors participate in the modulation of memory-related responses, especially those in which cholinergic pathways are implicated.

Cerium oxide nanoparticles (CNPs), owing to their antioxidant property, have recently emerged as therapeutic candidate for Alzheimer’s disease (AD). However, intravenous CNPs are limited due to their poor physicochemical properties, rapid blood clearance and poor blood–brain penetration. Thus, we developed intranasal CNPs and evaluated its potential in experimental AD. CNPs were synthesized using homogenous precipitation method and optimized through Box–Behnken Design. The formation of CNPs was confirmed by UV spectroscopy and FTIR. The optimized CNP were spherical, small (134.0 ± 3.35 nm), uniform (PDI, 0.158 ± 0.0019) and stable (ZP, −21.8 ± 4.94 mV). The presence of Ce in CNPs was confirmed by energy-dispersive X-ray analysis. Further, the X-ray diffraction spectra revealed that the CNPs were nano-crystalline. The DPPH assay showed that at concentration of 50 µg/mL, the percentage radical scavenging was 95.40 ± 0.006%. Results of the in vivo behavioral studies in the scopolamine-induced Alzheimer rat model showed that intranasal CNPs dose dependently reversed cognitive ability. At dose of 6 mg/kg the morris water maze results (escape latency, path length and dwell time) and passive avoidance results (retention latency) were significantly different from untreated group but not significantly different from positive control group (rivastigmine patch, 13.3 mg/24 h). Further, biochemical estimation showed that intranasal CNP upregulated the levels of SOD and GSH in brain. In conclusion, intranasal CNPs, through its antioxidant effect, could be a prospective therapeutics for the treatment of cognitive impairment in AD.

Schizophrenia is a chronic mental disorder that disturbs feelings and behavior. The symptoms of schizophrenia fall into three categories: positive, negative, and cognitive. Cognitive symptoms are characterized by memory loss or attentional deficits, and are especially difficult to treat. Thus, there is intense research into the development of new treatments for schizophrenia-related responses. One of the possible strategies is connected with cannabidiol (CBD), a cannabinoid compound. This research focuses on the role of CBD in different stages of memory (acquisition, consolidation, retrieval) connected with fear conditioning in the passive avoidance (PA) learning task in mice, as well as in the memory impairment typical of cognitive symptoms of schizophrenia. Memory impairment was provoked by an acute injection of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (animal model of schizophrenia). Our results revealed that an acute injection of CBD (30 mg/kg; intraperitoneally (i.p.) improved all phases of long-term fear memory in the PA test in mice. Moreover, the acute injection of non-effective doses of CBD (1 or 5 mg/kg; i.p.) attenuated the memory impairment provoked by MK-801 (0.6 mg/kg; i.p.) in the consolidation and retrieval stages of fear memory, but not in the acquisition of memory. The present findings confirm that CBD has a positive influence on memory and learning processes in mice, and reveals that this cannabinoid compound is able to attenuate memory impairment connected with hypofunction of glutamate transmission in a murine model of schizophrenia.

Objective: Zataria multiflora (Zm) has been proposed for memory enhancing in Persian traditional medicine; but to now, no study has been carried out in this field yet. The aim of this research was to study the plant effect on spatial memory in scopolamine-induced amnesia and investigate in vivo anticholinesterase effect of Zm. Material and Methods: Aerial parts of the plant were extracted with methanol and standardized on the basis of rutin content. Male rats received three doses of Zm extract (100, 200 and 400 mg/kg, intraperitoneal (ip) for 7 days) and 30 min after the latest dose, scopolamine (1 mg/kg) was administered to animals. Learning capacity and spatial memory were studied using morris water maze (MWM) and passive avoidance test (PAT) methods. Anticholinesterase activity was studied using Ellman's method. Physostigmine (0.3 mg/kg) and piracetam (200 mg/kg) were used as positive controls. Results: All doses of Zm extract significantly decreased the distance and time spent to find the platform in MWM and increased the time latency in PAT test. In both MWM and PAT tests, the highest effect of Zm was observed at 200 mg/kg which was in accordance with AChE inhibitory effect of the plant. Conclusion: Our findings indicate that Zm has anti-amnesic effect and might improve memory deficit through anticholinesterase activity. [ABSTRACT FROM AUTHOR]

• Chronic exposure to vitamin deficiency and a very low dose of pesticides mixture determine stimulation of SNC. • Chronic vitamin deficiency decreased locomotor and spatial orientation activity in rats. • Exposure to very low doses of a mixture of 6 pesticides caused an inhibition of the central nervous system. • Chronic vitamin deficiency and exposure to a very low dose of pesticides mixture affect long term memory. We investigate the long-term effect of very-low dose exposure to a mixture of six pesticides associated with hydrophilic vitamin deficiency on the neurobehavioral outcomes of rats. Two hundred Wistar rats were divided into four groups, two control groups, a vitamin sufficient control group and a vitamin deficiency control group and 2 test groups, a vitamin sufficient test group, and a vitamin deficiency group. The test groups were exposed for 9 months to a mixture of diquat, imazamox, imazethapyr, tepraloxydin, bentazone and acifluorfen in doses of 0.01xNOAEL (mg/kg bw/day). After 9 months of exposure, the behavior changes were evaluated by open field test and elevated plus maze test and the memory was assessed by passive avoidance test. Chronic vitamin deficiency decreased locomotor and special orientation activity and increased anxiety-like behavior in rats. Exposure to very low doses of a mixture of 6 pesticides caused central nervous effects, manifested as decreased locomotor activity, and increased anxiety levels. Vitamin deficiency and low dose chronic pesticides mixture exposure thus affected the central nervous system, especially long-term memory. [ABSTRACT FROM AUTHOR]

Emotions and memory formation are sensible to circadian rhythm. Here we study whether the time of day during the light phase of the diurnal cycle affects emotional memory in male Wistar rats using the passive avoidance (PA) test. Experiments were conducted at the beginning of Zeitgeber time (ZT) (ZT0.5-2), mid-time (ZT5-6.5), and end (ZT10.5-12) of the light period. Our results suggest that time of day has no impact on emotional response during acquisition trials, but slightly influences cognitive response during the 24-hour retention trial. Retention response was highest for ZT5-6.5, followed by ZT0.5-2, and lowest for ZT10.5-12. [ABSTRACT FROM AUTHOR]

Functional nutrition is a valuable supplementation to dietary therapy. Functional foods are enriched with biologically active substances. Plant polyphenols attract particular attention due to multiple beneficial properties attributed to their high antioxidant and other biological activities. We assessed the effect of grape polyphenols on the life span of C57BL/6 mice and on behavioral and neuroinflammatory alterations in a transgenic mouse model of Parkinson disease (PD) with overexpression of the A53T-mutant human α-synuclein. C57BL/6 mice were given a dietary supplement containing grape polyphenol concentrate (GPC—1.5 mL/kg/day) with drinking water from the age of 6–8 weeks for life. Transgenic PD mice received GPC beginning at the age of 10 weeks for four months. GPC significantly influenced the cumulative proportion of surviving and substantially augmented the average life span in mice. In the transgenic PD model, the grape polyphenol (GP) diet enhanced memory reconsolidation and diminished memory extinction in a passive avoidance test. Behavioral effects of GP treatment were accompanied by a decrease in α-synuclein accumulation in the frontal cortex and a reduction in the expression of neuroinflammatory markers (IBA1 and CD54) in the frontal cortex and hippocampus. Thus, a GP-rich diet is recommended as promising functional nutrition for aging people and patients with neurodegenerative disorders.

Background: Treatment of memory impairment associated with dementia such as Alzheimer′s disease is still inadequate and requires development of new drugs. Objective: The objective was to evaluate the memory enhancing effect of Celastrus paniculatus seed oil. Materials and Methods: C. paniculatus seed oil was mixed with equal amount of pure ghee and administered orally to mice in the dose of 200 mg/kg/day. Piracetam was used as a standard nootropic. Elevated plus maze and passive avoidance tests were used as a models to test spatial and fear memory respectively. Scopolamine (3 mg/kg, i.p.), was used as an amnestic agent. Results: Mice receiving C. paniculatus showed significant memory enhancement as compared to scopolamine group. The effect of C. paniculatus and combination of C. paniculatus with piracetam was comparable to that with piracetam alone. Conclusion: The present study demonstrates that C. paniculatus seed oil has memory enhancing effect and hence can be developed as a potential drug in the treatment of dementia.

Aims: The aim of the study was to investigate the effects of exposure to enriched environment (EE) on passive avoidance learning and hippocampal cellular morphology in rats exposed to chronic restraint stress. Materials and Methods: Adult male albino Wistar rats were assigned into the following groups: normal control (NC) remained undisturbed in their home cages; stressed group (S) subjected to restrained stress (6 h/day) followed by housing in standard housing for 21 days; And stressed + EE (S + EE) subjected to restrained stress followed by housing in EE for 21 days. On 22nd day, six animals from each of the three groups were exposed to passive avoidance test. The remaining animals were sacrificed. Hippocampus was isolated and processed for cellular morphology using cresyl violet staining. Statistical Analysis Used: Data were analyzed using one-way analysis of variance followed by Tukey's multiple comparison test (post hoc). Results: Stressed rats exposed to EE showed significant improvement in passive avoidance learning test compared to NC. Quantification of the surviving neurons in the hippocampal subfields and their cellular morphology revealed significant neuroprotection in S + EE in cornu ammonis-2 (CA2) neurons and CA3 hippocampal neurons. No significant changes were found in CA1 hippocampal subfield. Conclusions: The outcome of this study makes us to think the possibilities of adopting EE as an alternative strategy in brain diseases where there is chronic stress and to minimize the impairment in learning and memory. [ABSTRACT FROM AUTHOR]

In Mongolian gerbils, bilateral common carotid artery occlusion (BCCAO) for several minutes induces ischemia, due to an incomplete circle of Willis, resulting in delayed neuronal cell death in the Cornet d'Ammon 1 (CA1) region of the hippocampus. Neuronal cell death in the hippocampus and changes in behavior were examined after BCCAO was performed for 5 min in the gerbils. One day after BCCAO, the pyramidal neurons of the CA1 region of the hippocampus showed degenerative changes (clumped chromatin in nuclei). At 5 and 10 days after BCCAO, extensive neuronal cell death was observed in the hippocampal CA1 region. Cognitive performance was evaluated by using the radial maze and passive avoidance tests. In the radial maze test, which examines win-stay performance, the number of errors was significantly higher in ischemic gerbils than in sham-operated gerbils on days 1 and 2 post-operation. In the passive avoidance test, the latency and freezing times were significantly shorter in ischemic gerbils than in sham-operated gerbils on the days 1, 2, and 4-6 post-operation. These results indicate that transient forebrain ischemia impairs cognitive performance, even immediately after the ischemic insult when there are only subtle signs of neuronal cell death. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is a slowly progressive devasting neurodegenerative disorder of central nervous system manifested by deterioration of memory, cognitive functions, behaviour change and impairment in performing activities of daily life. Neurochemical studies of patients suffering from AD demonstrate selective loss of cholinergic neurons, low concentration of acetylcholine (Ach) in the selective areas of brain such as cortex and hippocampus. Objective: A series of new semicarbazones of 4-aminopyridine has been designed, synthesized and evaluated for cognition enhancing activities through the inhibition of acetylcholinesterase (AChE) and by passive avoidance model. Material and methods: In the present study, ten new 4-Aminopyridine analogues were synthesized and characterized by analytic methods such as UV, IR, NMR, elemental analysis and for their inhibitory role on Acetylcholinesterase activity by applying the molecular docking studies and performed enzyme kinetics study by Ellman's spectrophotometric method. The synthesized analogues were then evaluated for antiamnesic and cognition enhancing activities by passive avoidance test. Results: The results illustrated a significant cognition enhancing effect on passive avoidance test with a significant reversal of scopolamine-induced amnesia, which is comparable with standard drug rivastigmine. The in-vitro study of synthesized analogues showed maximum activity of compound-3 and compound-9 compared to standard drug rivastigmine, whereas its enzyme kinetic study revealed a non-competitive inhibition of acetylcholinesterase (AChE) is held responsible to a possible interaction of analogue with the peripheral anionic site (PAS) of AChE and was also confirmed by molecular docking studies. Conclusion: On the basis of present study, we are concluding that hydroxyl substituted Compound 3 and 9 identified as most potent drug which can leads to the discovery and development of new Cognition enhancers in near future. [ABSTRACT FROM AUTHOR]

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 < .001andp < .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 andp < .001, respectively) which improved by LA when it was administered before LPS in LA-LPS group (p < .05 andp < .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. [ABSTRACT FROM PUBLISHER]

Animal models of scopolamine-induced amnesia are widely used to study underlying mechanisms and treatment of cognitive impairment in neurodegenerative diseases such as Alzheimer's disease (AD). Previous studies have identified that melatonin improves cognitive dysfunction in animal models. In this study, using a mouse model of scopolamine-induced amnesia, we assessed spatial and short-term memory functions for 4 weeks, investigated the expression of myelin-basic protein (MBP) in the dentate gyrus, and examined whether melatonin and scopolamine cotreatment could keep cognitive function and MBP expression. In addition, to study functions of melatonin for keeping cognitive function and MBP expression, we examined expressions of brain-derived neurotrophic factor (BDNF) and tropomycin receptor kinase B (TrkB) in the mouse dentate gyrus. Scopolamine (1 mg/kg) and melatonin (10 mg/kg) were intraperitoneally treated for 2 and 4 weeks. Two and 4 weeks after scopolamine treatment, mice showed significant cognitive impairment; however, melatonin and scopolamine cotreatment recovered cognitive impairment. Two and 4 weeks of scopolamine treatment, the density of MBP immunoreactive myelinated nerve fibers was significantly decreased in the dentate gyrus; however, scopolamine and melatonin cotreatment significantly increased the scopolamine-induced reduction of MBP expression in the dentate gyrus. Furthermore, the cotreatment of scopolamine and melatonin significantly increased the scopolamine-induced decrease of BDNF and TrKB immunoreactivity in the dentate gyrus. Taken together, our results indicate that melatonin treatment exerts anti-amnesic effect and restores the scopolamine-induced reduction of MBP expression through increasing BDNF and TrkB expressions in the mouse dentate gyrus. [ABSTRACT FROM AUTHOR]

This study aims to investigate the frequency and total duration effects of the 2-week treadmill training after experimental ischemic stroke in the passive avoidance test. We performed bilateral occlusion of common external carotid arteries, for five minutes, in Mongolian gerbils. The training groups were: continuous training for twelve consecutive days or not continuous training for six non-consecutive days. The groups remained in the treadmill for 15 min, with the speed set at 10 m/min, and the training started 24 h after the stroke. In the Shuttle Box, each animal had ten trials during the Learning Session (LS), which occurred 24 h before the stroke. The Retention Test (RT) occurred 24 h after the stroke and started on the second, third, seventh and twelfth day after LS. After the experiments, the brains were perfused, and coronal sections of the CA1 area of the hippocampus were cut and stained with hematoxylin and eosin. ANOVA on Ranks was used for Behavioral data analysis and morphological data by percentage. Ischemic training groups showed preservation in neuron density in the CA1 area of the hippocampus, when compared to the control groups. Animals subjected to continuous training, showed a higher latency in the RT when compared to ischemic animals in both weeks [(2nd, H = 39.81; P < 0.05), (3rd, H = 38.08; P < 0.05), (7th, H = 44.17; P < 0.05), and (12th, H = 39.55; P < 0.05). Animals in the not continuous training showed higher latency in the RT, in the second week only [(2nd, H = 39.81; P < 0.05), (3rd, H = 38.08; P < 0.05), (7th, H = 44.17; P < 0.05), and (12th, H = 39.55; P < 0.05). These findings suggest that improvement of memory after stroke after treadmill training is dependent on the frequency and total duration of training. [ABSTRACT FROM AUTHOR]

The article presents the study of psycho- and neurotropic properties of novel 3-(N-R,R′-aminomethyl)-2-methyl-1H-quinolin-4-ones in vivo . The research was carried out using the open field test, elevated plus maze, rotarod test, tail suspension test, passive avoidance test after scopolamine-induced amnesia and acute normobaric hypoxia with hypercapnia. As a result, two promising substances have been found. According to our results 3-[[(4-methoxyphenyl)amino]methyl]-2-methyl-1H-quinolin-4-one in the dose of 10 mg/kg shows a specific sedative effect and a considerable anti-amnesic activity. The most interesting N-[(2-methyl-4-oxo-1H-quinolin-3-yl)methyl]-N-phenylbenzamide (100 mg/kg) combines a potent anti-anxiety action, the anti-amnesic activity and a considerable antihypoxic effect. They are of interest for further profound studies as promising psychoactive compounds. [ABSTRACT FROM AUTHOR]

Civilization diseases associated with memory disorders are important health problems occurring due to a prolonged life span. The manuscript shows the results of an in vivo study targeting the emergence of two drug candidates with anti-amnestic properties. The preceding quantitative structure-activity relationship (QSAR) studies provided information on the ability of berberine and magnoflorine to cross the blood-brain barrier (BBB). In the light of these findings, both compounds were purified from crude plant extracts of barberries: berberine--from Berberis siberica using a method published earlier, and magnoflorine--from Berberis cretica by centrifugal partition chromatography (solvent system: ethyl acetate:butanol:water-0.6:1.5:3 v/v/v). Both the compounds were evaluated for their memory enhancing and scopolamine inhibitory properties in an in vivo passive avoidance (PA) test on mice towards short-term and long-term memory. Cognition enhancing properties were observed at the following doses: 5 mg/kg (i.p.) for berberine and 20 mg/kg (i.p.) for magnoflorine. In addition, both the tested isoquinolines with the co-administered scopolamine were found to block long-term but not short-term memory impairment. No influence on the locomotor activity was observed for the tested doses. The results confirmed a marked central activity of magnoflorine and showed the necessity to lower the dosage of berberine. Optimized purification conditions have been elaborated for magnoflorine. [ABSTRACT FROM AUTHOR]

There is an increasing number of studies showing that occlusal dysfunction impairs learning and memory. We previously demonstrated that the brain has a mechanism to calibrate between the activities of spindle afferents and periodontal-mechanoreceptor afferents for controlling the chewing movement, and the accurate calibration can be done only at the proper vertical dimension of occlusion (VDO). Then, the chewing at an inappropriate VDO may induce a severe mental stress due to a mal-calibration. However, it is not clear how the impairment of learning/memory progresses over the period of stress induced by occlusal dysfunction. We investigated by passive avoidance test how the behavior and learning/memory are altered in guinea pigs in which the VDO was raised by 2–3 mm over the period up to 8 weeks. We found that the guinea pigs reared under the raised occlusal-condition (ROC) for 1 week showed a very high sensitivity to electrical stimulation whereas this did not cause the memory consolidation in the 1st-day retention trial, suggesting that such hypersensitivity rather hampered the fear learning. In the guinea pigs reared under the ROC for 2 and 8 weeks, the learning ability was not largely affected and memory consolidation occurred similarly whereas the memory retention deteriorated more severely in the latter guinea pigs than in the former ones. In the guinea pigs reared under the ROC for 3 and 4 weeks, learning was severely impaired, and memory consolidation did not occur. These results suggest that the occlusal dysfunction for varying periods differentially impairs learning and memory. • Occlusal dysfunction for one week caused a hypersensitivity to pain stimulation. • Occlusal dysfunction for 2 weeks moderately impaired memory retention. • Occlusal dysfunction for 3–4 weeks transiently impaired fear learning. • Occlusal dysfunction for 8 weeks impaired memory retention but not its acquisition. • Occlusal dysfunction for varying periods differentially impaired learning and memory. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is a neurodegenerative disorder that damages health and welfare of the elderly, and there has been no effective therapy for AD until now. It has been proved that tanshinone IIA (tan IIA) could alleviate pathological symptoms of AD via improving non-amyloidogenic cleavage of amyloid precursor protein, decreasing the accumulations of p-tau and amyloid-β1−42 (Aβ1−42), and so forth. However, the further biochemical mechanisms of tan IIA are not clear. The experiment was undertaken to explore metabolites of tan IIA in AD rats induced by microinjecting Aβ1-42 in the CA1 region of hippocampus. AD rats were orally administrated with tan IIA at 100 mg/kg weight, and plasma, urine, faeces, kidney, liver and brain were then collected for metabolites analysis by UHPLC-Q-Exactive Qrbitrap mass spectrometry. Consequently, a total of 37 metabolites were positively or putatively identified on the basis of mass fragmentation behavior, accurate mass measurements and retention times. As a result, methylation, hydroxylation, dehydration, decarbonylation, reduction reaction, glucuronidation, glycine linking and their composite reactions were characterized to illuminate metabolic pathways of tan IIA in vivo. Several metabolites presented differences in the distribution of tan IIA between the sham control and the AD model group. Overall, these results provided valuable references for research on metabolites of tan IIA in vivo and its probable active structure for exerting neuroprotection.