Effect of metformin on the spatial memory in aged rats

Background: Aging process is often accompanied with some degree of decline in all the abilities, including learning and memory. One of the attracting research fields has been devoted to finding antiaging drugs. Metformin has shown some memory-enhancing features in aged humans and laboratory animals. Aims and Objective: To evaluate the effects of 50, 75, and 100 mg/kg of metformin on the spatial memory performance of aged rats in the Morris water maze. Materials and Methods: Thirty-two male 24-month-old rats were divided randomly into four groups (n = 8) including control group and 50-, 75-, and 100-mg/kg metformin groups. After 36 days of treatment, the learning process was assessed by the reference memory task in the Morris water maze. All the rats received water maze training (four trials/day for 5 days) to assess the hippocampal-dependent spatial learning and, then, received a 60-s probe trial test of spatial memory retention 24 h after the twentieth trial. Result: Over 5 days of training, metformin (50, 75, and 100 mg/kg/day) treatment significantly reduced the latency and path length to find the escape platform (P < 0.01). In probe trials (without platform), on the last day of training, the metformin-treated groups spent significantly longer time in the platform quadrant when compared with the control group. Among the treated groups, 100 mg/kg dosage of metformin induced the best rehearsals memory (P < 0.05). Conclusion: These results showed that, in the old rats, 36-day orally administered metformin showed a positive influence on the spatial memory performance in the Morris water maze. © 2015 Farzaneh Ganji

EFEK NEUROPROTEKTIF KATEKIN GAMBIR (Uncaria gambir [Hunter] Roxb) TERHADAP PROTEIN TAU TERFOSFORILASI PADA TIKUS MODEL ALZHEIMER SPRAGUE DAWLEY BETINA

Penyakit Alzheimer merupakan penyakit neurokognitif kronik progresif yang ditandai dengan gangguan memori dan perilaku, dimana sebagian besar penderitanya adalah wanita. Gangguan kognitif pada Alzheimer disebabkan oleh hiperfosforilasi protein tau mikrotubul yang salah satunya diakibatkan oleh stres oksidatif. Katekin sebagai antioksidan poten dan bersifat neuroprotektif dikaitkan dengan modalitas tauopati pada penderita Alzheimer. Penelitian ini bertujuan untuk mengetahui efek neuroprotektif katekin gambir terhadap konsentrasi protein tau terfosforilasi (pTau) pada tikus model Alzheimer Sprague dawley betina. Penelitian eksperimental dengan post-test only group design ini menggunakan tikus model Sprague dawley betina yang diinduksi dengan ovariektomi dan pemberian d-galaktosa 500 mg/kgBB. Tikus yang mempunyai lokomotor > 6 dibagi menjadi lima kelompok yaitu kontrol negatif (KN), kontrol positif (KP) dan kelompok yang mendapatkan (+)-katekin dengan dosis 20 mg/ 200 gBB (KA1), 40 mg/ 200 gBB (KA2) dan 60 mg/ 200 gBB (KA3). Uji kognitif dinilai dengan persentase perubahan spontan (PPS) dilakukan menggunakan Y-maze dan konsentrasi pTau diukur dengan metoda ELISA. Analisis data menggunakan uji statistik dimana untuk menguji perbedaan rerata menggunakan Oneway ANOVA dan dilanjutkan dengan post hoc Bonferoni untuk data parametrik dan Games-Howell untuk data nonparametrik. Uji korelasi menggunakan Spearman-rho. Hasil analisis menunjukkan perbedaan rerata PPS signifikan pada KA2 (68,70±9,58) dan KA3 (81,50±4,98) dengan p masing-masing 0,022 dan 0,008. Konsentrasi pTau bermakna secara statistik pada KA3 dengan nilai 2,534±0,368 pg/ml lebih rendah dari KP 3,155±1,364 pg/ml (p=0,011). Terdapat korelasi berkekuatan sedang yang berpola negatif pTau terhadap PPS dengan r=-0,433 dan p=0,031 Kesimpulan dari hasil analisis efek neuroprotektif (+)-katekin terjadi melalui penurunan konsentrasi Tau terfosforilasi. Kata kunci: Alzheimer, gambir, katekin, neurokognitif, tauopat

Assessment of spatial memory and time perception in young people and elders, and the relationship of these cognitive abilities in episodic memory

Con las recientes investigaciones acerca de las células de lugar y de tiempo localizadas en el hipocampo, y de su involucración en la memoria espacial y la percepción temporal, se ha propuesto una relación entre ambas capacidades cognitivas para la construcción del contexto espacio-temporal de la memoria episódica. Asimismo, con los conocimientos acerca de los efectos del envejecimiento sobre el hipocampo, se puede hipotetizar que en las personas mayores las habilidades cognitivas mencionadas pueden verse alteradas. Para analizar esta supuesta relación entre capacidades, además de observar posibles diferencias en el rendimiento entre jóvenes y mayores, en este estudio se ha utilizado una batería online con una tarea de memoria espacial (Almeria Spatial Memory Recognition Test, o ASMRT) y una de percepción temporal (tarea de estimación de velocidad) en una muestra de 20 jóvenes y 20 personas mayores. Tras el análisis de los resultados obtenidos, se puede observar un mayor rendimiento por parte de los jóvenes en ambas pruebas, además de presentar estos una mayor adaptabilidad a las diferentes condiciones de la tarea de estimación de velocidad. Adicionalmente, de las correlaciones halladas se puede inferir cierta relación entre el rendimiento en las tareas de ambos grupos, donde una mejor ejecución en una prueba aumenta la probabilidad de un buen rendimiento en la otra. Esta investigación ha permitido seguir corroborando la diferencia predicha entre el rendimiento de jóvenes y personas mayores en tareas que implican memoria espacial y percepción temporal, además de colaborar en el asentamiento de bases para que futuras investigaciones continúen explorando esta conexión entre capacidades cognitivas

Effectiveness and cost-effectiveness of transmural collaborative care with consultation letter (TCCCL) and duloxetine for major depressive disorder (MDD) and (sub)chronic pain in collaboration with primary care: design of a randomized placebo-controlled multi-Centre trial: TCC:PAINDIP

__Abstract__ Background: The comorbidity of pain and depression is associated with high disease burden for patients in terms of disability, wellbeing, and use of medical care. Patients with major and minor depression often present themselves with pain to a general practitioner and recognition of depression in such cases is low, but evolving. Also, physical symptoms, including pain, in major depressive disorder, predict a poorer response to treatment. A multi-faceted, patient-tailored treatment programme, like collaborative care, is promising. However, treatment of chronic pain conditions in depressive patients has, so far, received limited attention in research. Cost effectiveness of an integrated approach of pain in depressed patients has not been studied. This article describes the aims and design of a study to evaluate effects and costs of collaborative care with the antidepressant duloxetine for patients with pain symptoms and a depressive disorder, compared to collaborative care with placebo and compared to duloxetine alone

Effects of Practice Type and Task Difficulty on Visuospatial Performance

The importance of visuospatial skills for every day survival is highly evident. Practice is a mechanism by which visuospatial skills can be enhanced. The current study examined how general practice, different types of practice, and levels of task difficulty affect visuospatial performance. Seventy-eight undergraduate students participated in the Block Design Task (extracted from the Wechsler Adult Intelligence Scale) in which they had to construct a design with the blocks based on a printed image. Prior to completing 40 test trials, participants received opportunities for motor (physical), mental (visualization), or modeling (observational) practice. Half of the trials contained easy designs, and the other half of trials contained difficult designs. Results indicate that participants benefitted from general practice across trials and that performance was dependent on task difficulty. However, there were no differences in performance due to type of practice. Overall, the results of this study implicate that practice aids in visuospatial performance, and that task difficulty is a mediating factor

Effects of Practice Type and Task Difficulty on Visuospatial Performance

The importance of visuospatial skills for every day survival is highly evident. Practice is a mechanism by which visuospatial skills can be enhanced. The current study examined how general practice, different types of practice, and levels of task difficulty affect visuospatial performance. Seventy-eight undergraduate students participated in the Block Design Task (extracted from the Wechsler Adult Intelligence Scale) in which they had to construct a design with the blocks based on a printed image. Prior to completing 40 test trials, participants received opportunities for motor (physical), mental (visualization), or modeling (observational) practice. Half of the trials contained easy designs, and the other half of trials contained difficult designs. Results indicate that participants benefitted from general practice across trials and that performance was dependent on task difficulty. However, there were no differences in performance due to type of practice. Overall, the results of this study implicate that practice aids in visuospatial performance, and that task difficulty is a mediating factor

Acetylcholine neuromodulation in normal and abnormal learning and memory: vigilance control in waking, sleep, autism, amnesia, and Alzheimer's disease

This article provides a unified mechanistic neural explanation of how learning, recognition, and cognition break down during Alzheimer's disease, medial temporal amnesia, and autism. It also clarifies whey there are often sleep disturbances during these disorders. A key mechanism is how acetylcholine modules vigilance control in cortical layer

Where's Waldo?® How perceptual, cognitive, and emotional brain processes cooperate during learning to categorize and find desired objects in a cluttered scene

The Where's Waldo problem concerns how individuals can rapidly scan a scene to detect a target object in it. This dissertation develops the ARTSCAN Search neural model to clarify how brain mechanisms that govern spatial and object attention, spatially-invariant object learning and recognition, reinforcement learning, and eye movement search are coordinated to enable learning and directed search for desired objects at specific locations in a cluttered scene. In the model, interactions from the Where cortical processing stream to the What cortical processing stream modulate invariant category learning of a desired object, whereas interactions from the What cortical processing stream to the Where cortical processing stream support search for the object. In particular, when an invariant object category representation is activated top-down by a cognitive plan or by an active motivational source in the model's What stream, it can shift spatial attention in the Where stream and thereby selectively activate the locations of sought-after object exemplars. These combined What-to-Where and Where-to-What interactions clarify how the brain's solution of the Where's Waldo problem overcomes the complementary deficiencies of What and Where stream processes taken individually by using inter-stream interactions that allow both invariant object recognition and spatially selective attention and action to occur

RAGE SIGNALING MEDIATES DEFICITS IN HIPPOCAMPAL FUNCTION IN MODELS OF DIABETES

Diabetes is a prevalent metabolic disorder that affects various body functions and systems. Effects of diabetes on cognitive function have been reported in animal models of diabetes, particularly learning and memory impairments and changes in hippocampal synaptic plasticity such as long-term potentiation (LTP), which depends primarily on NMDA and AMPA subtypes of glutamate receptors. The Receptor for Advanced Glycation End-products (RAGE) has been particularly implicated in vascular and peripheral nervous system complications of diabetes. These observations led us to hypothesize that RAGE signaling in models of diabetes can alter the function of NMDA and AMPA subtypes of glutamate receptors, leading to dysfunction in synaptic transmission and subsequent impairment in learning and memory. Our findings showed that although recognition memory was unaffected in streptozotocin (STZ)-induced diabetes in both genotypes, hippocampal-dependent spatial memory was impaired in STZ-induced diabetic mice in wild-type (WT) but not in the RAGE knockout (RAGE-KO) group. This impairment in spatial memory was consistent with deficits in synaptic plasticity, i.e. LTP and paired pulse facilitation (PPF), and reduction in the expression and phosphorylation of the GluA1 subunit of the AMPA receptor in WT STZ-induced diabetic mice. These changes were associated with the activation of the mitogen activated protein kinase (MAPK) pathway, leading to increased total p38, phospho-p38, and nuclear factor-kappa beta (NF-κB) and decreased phospho c-Jun N-terminal kinase (pJNK) and its kinase, mitogen activated protein kinase kinase 7 (pMEK7). In WT hippocampal cultures, high glucose caused a reduction of AMPA-evoked currents, as well as a reduction in cell excitability, and an increase in cytosolic ROS. This is the first study, to the best of our knowledge, that shows the contribution of RAGE signaling in abnormal hippocampal synaptic transmission and cognitive function in diabetes, which could help identify potential targets for therapeutic interventions