Improved effect and underlying mechanism of methylene blue on cognitive function in brain-inflammatory-aging rats / 中华老年心脑血管病杂志

Objective To determine the improved effect of methylene blue(MB)on cognitive func-tion in brain-inflammatory-aging rats and investigate the underlying mechanism.Methods A total of 38 healthy 12-month-old SD rats were randomly divided into healthy control group,lipopo-lysaccharide(LPS)group,MB vehicle group and MB group,with 8 rats in the control and 10 rats in the other three groups.LPS was injected into the fourth ventricle with aid of a subcutaneous sustained release pump to establish a rat model of brain chronic inflammatory aging.MB of 0.5 mg/(kg·d)was added into the pump in the rats from the MB group.T-maze test and new object recognition test were employed to evaluate the learning and memory abilities of the rats.The acti-vation of microglia and astrocytes in the hippocampal CA1 region of the rats was detected by im-munofluorescence assay.The release of inflammatory factors IL-1β and IL-6 was measured by ELISA,and neuronal death in the CA1 region was assessed by neuronal nuclei(NeuN)fluores-cence staining.Results There was no significant difference in the exploration time for new and old objects between the LPS group and the MB solvent group(P＞0.05).The MB group spent significantly longer time in exploring the new objects than the old object(22.50±4.32 s vs 11.60± 3.01 s,P=0.000).The alternating selection rate of new arm and expression level of NeuN antigen were significantly decreased,and the expression levels of ionized calcium binding adaptor mole-cule-1(Iba-1)and glial fibrillary acidic protein(GFAP)and the contents of IL-1β and IL-6 were obviously increased(P＜0.05)in the LPS group and the MB vehicle group than the healthy con-trol group.Compared with the MB vehicle group,the MB group had notably increased alternating selection rate of new arms and higher NeuN expression level,and decreased Iba-1 and GFAP ex-pression and IL-1β and IL-6 contents(P＜0.05).Conclusion Subcutaneous administration of MB could significantly inhibit the damages of spatial learning and memory abilities in the LPS-induced brain chronic inflammatory aging rats.The mechanism may be closely associated with MB inhibi-ting inflammatory glial cells and protecting hippocampal pyramidal neurons.

Safety assessment of multiple repeated percutaneous punctures for the collection of cerebrospinal fluid in rats

The objective of this study was to examine the safety of multiple repeated percutaneous punctures of cisterna magna for collecting cerebrospinal fluid (CSF) and preliminarily determine the optimal time interval and volume at each collection. Sixty Wistar rats were randomly assigned to six groups: 10 d-0 μL, 10 d-100 μL (100 μL CSF collected at an interval of 10 days), 10 d-150 μL, 15 d-0 μL, 15 d-100 μL, and 15 d-150 μL. CSF was collected by percutaneous puncture of the cisterna magna at four time-points. Simultaneously, locomotor activity, cisterna magna pressure, and acetylcholine levels in the CSF were monitored. Compared with the 10 d-0 μL group, the escape latency by Morris water maze was significantly prolonged in the 10 d-100 μL and 10 d-150 μL groups (P<0.05). Compared with the 15 d-0 μL group, the indices of 15 d-100 μL and 15 d-150 μL groups had no significant differences. When compared with that at the first training, the exception of the 10 d-150 μL and 15 d-150 μL groups, significant differences in escape latency were found at the 6th attempt (P<0.05). Compared with baseline readings for each group, the cisterna magna pressure in the 10 d-150 μL group began to decrease significantly from the third measurement (P<0.05). The optimal time interval during four CSF collections (100 μL per collection) via cisterna magna percutaneous puncture was determined to be 15 days. The procedure did not significantly affect learning processes, performance, or other related indices.

Differential Effects of Pentoxifylline on Learning and Memory Impairment Induced by Hypoxic-ischemic Brain Injury in Rats

OBJECTIVE: Hypoxic-ischemic (HI) brain injury in the human perinatal period often leads to significant long-term neurobehavioral dysfunction in the cognitive and sensory-motor domains. Using a neonatal HI injury model (unilateral carotid ligation followed by hypoxia) in postnatal day seven rats, the present study investigated the long-term effects of HI and potential behavioral protective effect of pentoxifylline. METHODS: Seven-day-old rats underwent right carotid ligation, followed by hypoxia (FiO2 = 0.08). Rats received pentoxifylline immediately after and again 2 hours after hypoxia (two doses, 60–100 mg/kg/dose), or serum physiologic. Another set of seven-day-old rats was included to sham group exposed to surgical stress but not ligated. These rats were tested for spatial learning and memory on the simple place task in the Morris water maze from postnatal days 77 to 85. RESULTS: HI rats displayed significant tissue loss in the right hippocampus, as well as severe spatial memory deficits. Low-dose treatment with pentoxifylline resulted in significant protection against both HI-induced hippocampus tissue losses and spatial memory impairments. Beneficial effects are, however, negated if pentoxifylline is administered at high dose. CONCLUSION: These findings indicate that unilateral HI brain injury in a neonatal rodent model is associated with cognitive deficits, and that low dose pentoxifylline treatment is protective against spatial memory impairment.

Black Rice (Oryza sativa L., Poaceae) Extract Reduces Hippocampal Neuronal Cell Death Induced by Transient Global Cerebral Ischemia in Mice

Rice is the most commonly consumed grain in the world. Black rice has been suggested to contain various bioactive compounds including anthocyanin antioxidants. There is currently little information about the nutritional benefits of black rice on brain pathology. Here, we investigated the effects of black rice (Oryza sativa L., Poaceae) extract (BRE) on the hippocampal neuronal damage induced by ischemic insult. BRE (300 mg/kg) was orally administered to adult male C57BL/6 mice once a day for 21 days. Bilateral common carotid artery occlusion (BCCAO) was performed for 23 min on the 8th day of BRE or vehicle administration. Histological analyses conducted on the 22nd day of BRE or vehicle administration revealed that administering BRE profoundly attenuated neuronal cell death, inhibited reactive astrogliosis, and prevented loss of glutathione peroxidase expression in the hippocampus when compared to vehicle treatment. In addition, BRE considerably ameliorated BCCAO-induced memory impairment on the Morris water maze test from the 15th day to the 22nd day of BRE or vehicle administration. These results indicate that chronic administration of BRE is potentially beneficial in cerebral ischemia.

Inhibitory effect of Thymus vulgaris extract on memory impairment induced by scopolamine in rat

Objective: To investigate the effect of Thymus vulgaris (. T. vulgaris) on learning and memory functions in scopolamine-induced memory deficit in rats. Memory enhancing activity in scopolamine-induced amnesic rats was investigated by assessing the Morris water maze and passive avoidance paradigm. Methods: A total of 42 male Wistar rats were divided into 6 equal groups as follow: control group: received water, scopolamine treated group: received scopolamine 1 mg/kg for 15 days, two scopolamine + T. vulgaris treated groups: received scopolamine and T. vulgaris extract 50 and 100 mg/kg body weight per day for 15 days, two intact groups: received T. vulgaris extract 50 and 100 mg/kg body weight per day for 15 days. Results: Administration of T. vulgaris extract significantly restored memory and learning impairments induced by scopolamine in the passive avoidance test and Morris water maze test. Conclusions: T. vulgaris extract has repairing effects on memory and behavioral disorders produced by scopolamine and may have beneficial effects in the treatment of Alzheimer's disease.

Inhibitory effect ofThymus vulgaris extract on memory impairment induced by scopolamine in rat

Objective:To investigate the effect ofThymus vulgaris (T. vulgaris) on learning and memory functions in scopolamine-induced memory deficit in rats. Memory enhancing activity in scopolamine-induced amnesic rats was investigated by assessing the Morris water maze and passive avoidance paradigm. Methods:A total of 42 male Wistar rats were divided into 6 equal groups as follow: control group: received water, scopolamine treated group: received scopolamine 1 mg/kg for 15 days, two scopolamine+T. vulgaris treated groups: received scopolamine andT. vulgaris extract 50 and 100 mg/kg body weight per day for 15 days, two intact groups: receivedT. vulgaris extract 50 and 100 mg/kg body weight per day for 15 days. Results: Administration ofT. vulgaris extract significantly restored memory and learning impairments induced by scopolamine in the passive avoidance test and Morris water maze test. Conclusions:T. vulgaris extract has repairing effects on memory and behavioral disorders produced by scopolamine and may have beneficial effects in the treatment of Alzheimer's disease.

Effect of bexarotene on spatial cognition, impairment in memory and learning and hippocampal nerve regeneration of Aβ25-35 mice / 中华神经医学杂志

Objective To explore the effect of bexarotene (BEX) on spatial cognition,impairment in memory and learning and hippocampal nerve regeneration of Aβ25-35 mice.Methods Eighty healthy male ICR mice were randomly divided into control group,model group,low-dosage BEX treatment group and high-dosage BEX treatment group (n=20); AD mouse models in the later three groups were induced by intracerebroventricular injection of Aβ25-35; and mice in the low-dosage BEX treatment group and high-dosage BEX treatment group treated with BEX (50 and 100 mg/kg·d) by gavage 7 days after Aβ25-35 injection for consecutive 14 days.Morris water maze and Y-maze tests were used to test the spatial cognitive function and abilities of learning and memory,respectively,28 days after Aβ25-35 injection.Intraperitoneal injection of 5-bromodeoxyuridine (BrdU) three times daily for 28 days was performed,and then,immumohistochemical staining was employed to detect the BrdU expression in the hippocampus; dual cortex protein (DCX) staining and Hoechst staining were,respectively,used to evaluate the proliferation and migration,and apoptosis of neuronal precursor cells; toluidine blue staining was employed to evaluate the mature neurons in the hippocampus.The levels of hippocampal brain-derived neurotrophic factor (BDNF) and the expressions of hippocampal glial fibrillary acidic protein (GFAP) and growth associated protein-43 (GAP-43) were measured by ELISA and Western blotting,respectively.Results Morris water maze test showed that the latency of crossing the platform was gradually increased in the control group,high-dosage BEX treatment group,low-dosage BEX treatment group and model group on the 3nd,4th,5th and 6th day,and the duration of stay was gradually decreased on the 6th day; increased learning frequency and reduced memory frequency was noted in Y-maze test; number of BrdU-positive cells,length and density of DCX neurite,and number of granule cells in the hippocampus decreased gradually,while Hoechst-positive cells decreased gradually; hippocampal levels of GFAP,GAP-43 and BDNF decreased gradually; the differences in the above levels were statistically significant (P＜0.05).Conclusion BEX can improve the spatial cognition and the impairment in memory and learning and promote their hippocampal neurogenesis of Aβ25-35 mice.

Effects of short-term enriched environment on the hippocampal formation and the myelinated fibers in the hippocampal formation of mid-aged female rats / 解剖学报

ObjectiveTo investigate the effects of short-term enriched environment on the hippocampal formation and the myelinated fibers in the hippocampal formation of mid-aged female rats. Methods Twenty 14-month female SD rats were randomly divided into 10 enriched environment (EE) rats and 10 standard environment (SE) rats. EE rats were reared in enriched environment and SE rats were reared in standard environment for 4 months. Then, five rats were randomly selected from each group. The spatial learning capacity was assessed with Morris water maze. The hippocampal formation and the myelinated fibers in the rat hippocampal formation were quantitatively investigated with transmission electronic microscopy technique and stereological methods. Results Short-term enriched environment enhanced the spatial learning capacity of the mid-aged female rats. The total length and total volume of the myelinated fibers in the hippocampal formation of the EE rats was significantly increased by 43.3% and 47.4%, respectively, when compared to the SE rats. There was no significant difference in the hippocampal volume and the mean diameter of the myelinated fibers in the hippocampal formation between two groups. The increase of the total length of the myelinated nerve fibers in the hippocampal formation was mainly due to the increase of the myelinated fibers with small diameter. Conclusion Short-term enriched environment had significant effects on the spatial learning capacity and the myelinated fibers in the hippocampal formation of middle-aged female rats.

Memoria y apreniizaje en la escogencia floral de lasaabejas / Memory And Learning In Bees' Floral Choices

Los polinizadores altamente especializados en su dieta, no hacen escogencias florales, ellos visitan un recurso específico siguiendo el dictado de la información almacenada en sus genes. En contraste, para la abeja social Apis mellifera una escogencia floral implica, la toma de una decisión, usualmente con criterio económico, basada en información aprendida y almacenada en alguna forma de memoria. Aunque existen numerosos estudios y modelos sobre la escogencia floral en abejas, la gran mayoría de éstos, han derivado sus conclusiones a partir de condiciones temporalmente fijas de la interacción. Muy pocos estudios han abordado la dinámica propia del contexto ecológico, en el cual el mercado floral de las abejas cambia con las estaciones del año y con los patrones diarios de antesis floral. Este cambio en la disponibilidad de especies florales enfrenta a los polinizadores, a realizar escogencias secuenciales acerca del alimento a explotar. En este trabajo abordo el tema del forrajeo secuencial en parches florales heterospecíficos, enfocándome en el uso que la abeja melífera hace de la información previamente aprendida en un contexto, cuando se enfrenta a la explotación de alimento en un contexto ecológicamente diferente. He realizado experimentos sobre escogencia floral simulando las condiciones de cambio del paisaje floral, exponiendo abejas individuales de A. mellifera a decidir sobre cuales especies forrajear en cada parche. Los resultados indican que la abeja invierte en procesos de aprendizaje en un muestreo inicial, pero una vez almacenada la información, utiliza una pieza de la información previamente aprendida (color) para explotar parches florales heteroespecíficos siguiendo una imagen de búsqueda de color. En esta revisión discuto situaciones biológicas de la interacción planta-abeja, las cuales apoyan la idea que en la naturaleza el uso de imágenes de búsqueda de color por parte de abejas sociales puede ser más común de lo que hasta ahora se ha pensado. Beneficios y costos se derivan de este comportamiento.

Pollinators highly specialized in their diet do not make food choices by means of cognitive processes; they just follow the dictate writing in their genes. Contrary, for the social bee Apis mellifera a floral choice implies to make a decision, usually following an economic criterion, based on information acquired from the environment and stored in some form of memory. Although there are numerous studies and models about floral choice in bees, most of them have derived their conclusions from 'static' conditions of the interaction. Rarely those studies have considered the dynamics of the ecological context, in which seasonality and daily rhythms in floral anthesis change the floral market for the bees. The change in flower species composition faces the pollinators to make sequential choices about what plant species to exploit in each case. In this paper I enter the subject about sequential foraging on heterospecific floral patches, focusing on the use that the bee A. mellifera makes of the information previously learned in a context, when the same bee face food exploitation in a completely different ecological context. I have done some experiments simulating two different floral patches, and exposing individuals of A. mellifera to decide about what floral resource to forage in each patch. The results indicate that the bee initially samples alternatives and they do invest on cognitive process to learn about the best flower species, but once this information is stored in the bee's memory, the bee takes a piece of the learned information (color), to use it as a search image while exploiting heterospecific floral patches. In this paper I discuss biological situations, which support the idea that in nature the use of a color search images by social bees, can be more common than it was thought initially. Cost and benefits are derived from this behavior.