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ABSTRACT In this study, the effect of thymoquinone (TQ) on propylthiouracil (PTU)-induced memory impairment was investigated in juvenile rats. The rats were grouped into control, Hypo, Hypo-TQ5 and Hypo-TQ10. Propylthiouracil increased latency time in the Morris water maze test and decreased delay in entering the dark compartment in the passive avoidance test. Both 5 mg/kg and 10 mg/kg doses of TQ decreased latency time in the Morris water maze test and increased delay in entering the dark compartment in a passive avoidance test. The PTU also increased malondialdehyde and nitric oxide metabolites in the brain while reduced the thiol content and superoxide dismutase and catalase activities and serum T4 level. Both doses of TQ decreased malondialdehyde and nitric oxide metabolites in the brain while enhanced the thiol content and superoxide dismutase and catalase activities and serum T4 level. The results of the present study showed that TQ protected against PTU-induced memory impairments in rats.

RESUMO Neste estudo, foi investigado o efeito da timoquinona (TQ) contra deficiências de memória induzidas por propiltiouracilo (PTU) em ratos juvenis. Os ratos foram agrupados em grupos: controle, Hypo, Hypo-TQ5, e Hypo-TQ10. O PTU aumentou o tempo de latência no teste do labirinto aquático de Morris (MWM) e diminuiu o atraso para entrar no compartimento escuro no teste de evasão passiva (PA). Ambas as doses de TQ diminuíram o tempo de latência no teste de MWM e aumentaram o atraso para entrar no compartimento escuro no teste de PA. O PTU também aumentou os metabolitos de malondialdeído (MDA) e óxido nítrico (NO) no cérebro, enquanto reduziu o teor de tiol e as atividades de superóxido dismutasa (SOD) e catalasa (CAT) e o nível sérico de T4. Ambas as doses de TQ diminuíram os metabolitos de MDA e de NO no cérebro, aumentaram o conteúdo de tiol e as atividades de SOD e CAT e o nível de T4 no soro. Os resultados do presente estudo mostraram que a TQ protegeu contra deficiências de memória induzidas por PTU em ratos.

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ABSTRACT Objective Increasing evidence demonstrates that oxidative stress and inflammatory are involved in amyloid β (Aβ)-induced memory impairments. Ursolic acid (UA), a triterpenoid compound, has potent anti-inflammatory and antioxidant activities. However, it remains unclear whether UA attenuates Aβ-induced neurotoxicity. Method The aggregated Aβ25-35 was intracerebroventricularly administered to mice. Results We found that UA significantly reversed the Aβ25-35-induced learning and memory deficits. Our results indicated that one of the potential mechanisms of the neuroprotective effect was attenuating the Aβ25-35-induced accumulation of malondialdehyde (MDA) and depletion of glutathione (GSH) in the hippocampus. Furthermore, UA significantly suppressed the upregulation of IL-1β, IL-6, and tumor necrosis-α factor levels in the hippocampus of Aβ25-35-treated mice. Conclusion These findings suggest that UA prevents memory impairment through amelioration of oxidative stress, inflammatory response and may offer a novel therapeutic strategy for the treatment of Alzheimer’s disease.

RESUMO Objetivo Há evidências crescentes de que o estresse oxidativo e a inflamação estão envolvidos na perda de memória induzida pelo peptídeo beta-amilóide (βA). O ácido ursólico (AU), um composto triterpenóide, apresenta atividades anti-inflamatórias e antioxidantes potentes. Entretanto, não se sabe ainda se o AU atenua a neurotoxicidade induzida pelo βA. Método O agregado βA 25-35 foi administrado aos ratos por via intracerebroventricular. Resultados Observou-se que o AU reverteu significativamente os déficits de aprendizado e de memória induzidos pelo βA 25-35. Portanto, um dos potenciais mecanismos do efeito neuroprotetor seria a atenuação do acúmulo de malondialdeído e a depleção de glutationa no hipocampo induzidos pelo βA 25-35. Além disso, o AU suprimiu significativamente a supra regulação dos níveis de IL-1β, IL-6 e do fator de necrose tumoral α no hipocampo dos ratos tratados com βA 25-35. Conclusão Esses achados sugerem que o AU previne a perda de memória através da melhora do estresse oxidativo e da resposta inflamatória, podendoproporcionar uma nova estratégia terapêutica para o tratamento da doença de Alzheimer.

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Inflammation and oxidative stress have important roles in memory impairment. The effect of 7-nitroindazole (7NI) on lipopolysaccharide (LPS)-induced memory impairment was investigated. Rats were used, divided into four groups that were treated as follows: (1) control (saline); (2) LPS; (3) 7NI-LPS; and (4) 7NI before passive avoidance (PA). In the LPS group, the latency for entering the dark compartment was shorter than in the controls (p < 0.01 and p < 0.001); while in the 7NI-LPS group, it was longer than in the LPS group (p < 0.01 and p < 0.001). Malondialdehyde (MDA) and nitric oxide (NO) metabolite concentrations in the brain tissues of the LPS group were higher than in the controls (p < 0.001 and p < 0.05); while in the 7NI-LPS group, they were lower than in the LPS group (p < 0.001 and p < 0.05, respectively). The thiol content in the brain of the LPS group was lower than in the controls (p < 0.001); while in the 7NI-LPS group, it was higher than in the LPS group (p < 0.001). It is suggested that brain tissue oxidative damage and NO elevation have a role in the deleterious effects of LPS on memory retention that are preventable using 7NI.

Inflamação e estresse oxidativo tem importante papel no déficit de memória. O efeito do 7-nitroindazol (7NI) no déficit de memória induzido por lipossacarídeos (LPS) foi investigado. Foram utilizados ratos que foram divididos em quatro grupos e tratados da seguinte maneira: (1) controles (solução salina); (2) LPS; (3) 7NI-LPS; e (4) 7NI antes da esquiva passiva (PA). No grupo LPS, a latência para entrar no compartimento escuro foi mais curta que nos controles (p < 0,01 e p < 0,001); enquanto no grupo 7NI-LPS, a latência foi maior que aquela do grupo LPS (p < 0,01 e p < 0,001). Concentrações de malondialdeído (MDA) e metabólitos do ácido nítrico (NO) no tecido cerebral do grupo LPS foram maiores que aquelas dos controles (p < 0,001 e p < 0,05); enquanto no grupo 7NI-LPS, as concentrações foram menores do que no grupo LPS (p < 0,001 e p < 0,05, respectivamente). O conteúdo cerebral de tiol no grupo LPS foi menos do que nos controles (p < 0,001); enquanto no grupo 7NI-LPS, este conteúdo foi maior que no grupo LPS (p < 0,001). Sugere-se que o dano oxidativo cerebral e o aumento de NO tenham um papel nos efeitos deteriorativos dos LPS na memória de retenção, e que isto possa ser prevenido com o uso de 7NI.

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We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each). The model group received 60% (v/v) ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N) and microglia (by Ib1) were conducted. Glutamic acid (Glu) and gamma amino butyric acid (GABA) in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC), and tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05) by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01), and neurons were reduced only in the hippocampal dentate gyrus (P<0.01) in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05), and Glu/GABA, TNF-α, and IL-1β increased (P<0.01) with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.

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This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

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Pioglitazone from thiazolidinediones generation, represent a new antidiabetic drugs that have been introduced in the world recently. Thiazolidinediones can improve insulin resistance by activating the nuclear peroxoxisome proliferator activated receptor-gamma [PPAR-gamma] and increasing insulin sensitivity in their receptors. Insulin and its receptors are found in specific areas of CNS with a variety of region-specific functions. The effects of insulin in CNS are different from its direct glucose regulation in the periphery. Hippocampus and cerebral cortex distributed insulin/insulin receptor have been shown to be involved in brain cognitive functions. In the present study, the effect of pioglitazone microinjection into CA1 region of rat hippocampus using Morris water maze performance has been investigated. In this experimental study, male N-MRI rats were randomly divided into control, DMF [dimethyl formamide] and pioglitazone groups [0.001, 0.01, 0.1, 1, 10 microg/rat]. Drugs were injected [1 microl/rat] into CA1 region bilaterly during 1 min. Thirty minutes after the intrahippocampal injection of drugs, water maze training was started. Pioglitazone had a dose dependent effect. The spatial learning and memory didn't change with lower dose of pioglitazone, but improved with intermediate doses, while they impaired with higher dose. These results suggest that intrahippocampal injection of pioglitazone may have a dose-dependent effect on spatial learning and memory in rats in range of 0.001 to 1 microg/rat

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Numerous observations in clinical and preclinical studies indicate that the developing brain is particularly sensitive to lead [PB]'s pernicious effects. The effects of low concentrations of lead on neurodevelopment are complicated. Lead acetate can disrupt both the CNS activity and neurons development. The present study was carried out to assess the effect of low level lead exposure on learning and memory by active avoidance learning. This experimental study was conducted at the Islamic Azad University of Parand in 2008. Eight groups of NMRI rats [9 rats in each group] [weight 220 +/- 30 gr] consisting of six experimental groups [3 after infancy and 3 adult groups] were exposed to low concentrations of lead for 45 days. The drinking water of the experimental groups was replaced by 0.05%, 0.1% and 0.2% of lead acetate solution whereas the two control groups received distilled water. The results were analyzed using the SPSS software and student t-test. In this study, the learning and memory tests showed no significant differences between experimental groups [infancy and adulthood] and infancy control and adult control in number of shocks for 0.05% concentration of lead acetate. The memory test showed an increase in number of shocks for 0.1% and 0.2% concentration of lead acetate in adult groups and an increase in number of shocks for 0.2% concentration of lead acetate in infancy groups [P<0.05]. The learning test showed an increase in number of shocks for 0.2% concentration of lead acetate in infancy groups [P<0.05]. Mechanisms of lead poisoning in the CNS are not clear; and it as been suggested that lead exposure during life alters the granule cell neurogenesis and morphology in the hippocampus of infant or young adult rats

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Dementia is one of the age related mental problems and a characteristic symptom of various neurodegenerative disorders including Alzheimer's disease. Certain drugs like diazepam, barbiturates and alcohol disrupt learning and memory in animals and man. However, a new class of drugs known as nootropic agents is now used in situations where there is organic disorder in learning abilities. The present work was undertaken to assess the potential of O. sanctum extract as a nootropic and anti-amnesic agent in mice. Aqueous extract of dried whole plant of O. sanctum ameliorated the amnesic effect of scopolamine (0.4 mg/kg), diazepam (1 mg/kg) and aging induced memory deficits in mice. Elevated plus maze and passive avoidance paradigm served as the exteroceptive behavioral models. O. sanctum extract decreased transfer latency and increased step down latency, when compared to control (piracetam treated), scopolamine and aged groups of mice significantly. O. sanctum preparations could of beneficial in the treatment of cognitive disorders such as dementia and Alzheimer's disease.

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In the present study, the effect of antioxidants-alpha lipoic acid, melatonin and trans resveratrol were studied against intracerebroventricular streptozotocin induced spatial memory deficit. Male Wistar rats were injected with intracerebroventricular streptozotocin bilaterally. The rats were treated chronically with alpha lipoic acid (200 mg/kg, po), melatonin (20 mg/kg, ip) and trans resveratrol (20 mg/kg, ip) for 18 days starting from day 1 of streptozotocin injection in separate groups. The spatial memory was evaluated using the Morris water maze task. The intracerebroventricular streptozotocin rats treated with antioxidants showed significantly less spatial memory deficit both in the acquisition and probe trials as compared to the vehicle treated rats. The study demonstrated the effectiveness of alpha lipoic acid, melatonin and trans resveratrol in preventing spatial memory deficit induced by intracerebroventricular streptozotocin and it's potential in age related neurodegenerative disorders where oxidative stress is involved such as Alzheimer's disease.

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Effect of ondansetron (5-HT3-receptor antagonist) was studied on the working memory deficits induced by scopolamine, a muscarinic receptor antagonist in rats using a three-panel runway apparatus. Varying doses of scopolamine (0.1-0.56mg/kg, ip) were administered alone or in combination with ondansetron (0.01-1.0 mg/kg, ip) and memory errors and latency period of the session were recorded on a three-panel runway apparatus. Treatment with scopolamine (0.56 mg/kg) produced working memory deficits in rats. Treatment with ondansetron (1.0 mg/kg) significantly reduced the scopolamine-induced working memory deficits.

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Nitric oxide (NO) has been demonstrated to enhance memory formation in experimental animals. However, the effect of NO precursor, L-arginine has never been tested on the memory impairing action of the aniepileptic drug, phenobarbitone independently and concurrently with the convulsant, picrotoxin (PCT). In view of this, in the present study, rats that acquired the shock avoidance task were treated with PCT (5 mg/ kg). Twenty four h later these animals were injected with L-arginine (500, 1000 mg/kg) and phenobarbitone (10, 20 mg/kg). Retention of the acquired task was tested 30 min later. The effect of these compounds were correlated with the changes produced by them on the concentration of NO in the brain. PCT and phenobarbitone (20 mg/kg) inhibited memory process independently and concurrently. NO concentration was not altered by phenobarbitone but was decreased in PCT-treated animals. L-arginine (1000 mg/kg) increased the concentration of NO in PCT and phenobarbitone treated animals and prevented these compounds from impairing memory process independently and concurrently. These results lead to a conclusion that L-arginine may be used in combination with phenobarbitone to prevent both the cognitive side effect of the antiepileptic drug and the impairment of memory that is associated with the convulsion disorder.

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Isatin (2,3-dioxoindole), one of the components of tribulin, which has been postulated to function as an endogenous marker of stress and anxiety, was shown to induce a dose-related attenuation of learning acquisition in an active avoidance test and inhibition of learning retention, or memory, in a step-down passive avoidance paradigm and transfer latency in an elevated plus-maze, in rats. Earlier studies have indicated that isatin functions as a 5-hydroxytryptamine (5-HT)3 receptor agonist in its anxiogenic activity in rats and is an antagonist at mammalian atrial natriuretic peptide (ANP) receptors. Since 5-HT3 receptor antagonists and centrally administered ANP have been shown to facilitate learning and memory, the observed memory dysfunction induced by isatin can be attributed to its receptor activity at 5-HT3 and ANP receptors. The investigation also indicates that anxiogenic agents are likely to disrupt memory functions.

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La eliminación de los efectos en el sistema nervioso central de los anéstesicos inhalatorios es un hecho fundamental en la recuperación de una anestesia general. En la clínica no evaluamos completamente este aspecto y sólo apreciamos la recuperación de conciencia. Objetivo: comparar el tiempo de recuperación de funciones intelectuales superiores entre dos anestésicos de uso clñinico habitual: enfluorano (E) v/s isofluorano (I). Material y métodos: seestudiaron dos grupos de 19 pacientes cada uno, entre 15 y 60 años, ASA 1 y 2, sometidos a colecistectomía laparoscópica. Se evaluó la función intelectual mediante el Mini Mental State de Folstein y Folstein, el cual cuenta con cuatro ítem: orientación, memoria, cálculo y coordinación, en el preoperatorio, y a la 1,2,4,8,y 24 hrs de suspendida la anestesia. Se eliminaron los pacientes con Mini Mental State (MMS) preoperatorio subnormal. Se premédico con dormonid, fentanyl y droperidol. Se indujo la anestesia con tiopental 4 a 6mg por kilo de peso y se realizó intubación orotraqueal bajo relajación neuromuscular con pancuronio o vecuronio. Se administró, según azar, I en el grupo 1 y E en el grupo 2, más N2O al 50 por ciento . Resultados: ambos grupos fueron comparables en cuanto a edad, sexo, peso, talla, duración de anestesia (99 v/s 105 min). En relación a la dosis de halogenados, el grupo con I recibió 2,2 MAC/hora y al grupo con E se le administró 1,6 MAC/hora, presentando diferencia estadísticamente significativa según test de Mann-Whitney. Para el análisis del MMS se usó test de Friedman, Wilcoxon y Mann-Whitney. Se compararon los test postoperatorios en relación al basal preoperatorio de cada paciente y se hizo comparación entre ambos grupos. La alteración de la función intelectual se encuentra en la 1ª, 2ª y 4ª hora en ambos grupos. Al analizar los subítem de cada test por separado, se observa sólo alteración en el grupo 2 (E), en el subítem de memoria, en la 1ª, 2ª y 4ª hora. En el grupo I(1) no se pesquisa alteraciones de éstos. Conclusiones: en nuestro grupo de pacientes la alteración intelectual es similar en ambos grupos, y permanece al menos 4 horas luego de la suspensión de los anestésicos. Se ha encontrado una diferencia cualitativa en cuanto a la función de la memoria, con una mayor alteración para el enfluorano

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Neste artigo, o segundo de uma série de três, prosseguimos na revisäo da segurança e tolerância dos benzodiazepínicos, analisando seu potencial de induzir déficit cognitivo global - agudo, sob a forma de delirium e crônico, na demência - e seletivo - ao interferirem no funcionamento normal da memória