rutin and Cognition-Disorders

Topics: Animals; Antioxidants; Brain; Cholesterol; Cognition Disorders; Humans; Hydroxyethylrutoside; Insulin Resistance; Mice

Increasing evidence demonstrates an association between diabetes and hippocampal neuron damage. This study aimed to determine the effects of troxerutin on cognitive deficits and glutamate cysteine ligase subunits (GCLM and GCLC) in the hippocampus of streptozotocin-induced type 1 diabetes mellitus (T1DM) rats. At 12weeks after streptozotocin injection, T1DM rats were randomly divided into 4 groups (n=15 each group) to receive no treatment (T1DM), saline (T1DM+saline), alpha-lipoic acid (T1DM+alpha-lipoic acid), and troxerutin (T1DM+troxerutin), respectively, for 6weeks. Meanwhile, 10 control animals (NC group) were assessed in parallel. Learning performance was evaluated by the Morris water maze. After treatment, hippocampi were collected for pathological examination by hematoxylin and eosin (H&E) staining. Next, hippocampal superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and glutathione (GSH) levels were assessed. Finally, glutamate cysteine ligase catalytic (GCLC) and glutamate cysteine ligase modifier (GCLM) subunit mRNA and protein levels were quantified by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. Compared with T1DM and T1DM+saline groups, escape latency was overtly reduced in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. Significantly increased GCLM and GCLC mRNA levels, GCLC protein amounts, SOD activity, and GSH levels, and reduced MDA amounts were observed in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. In T1DM and T1DM+saline groups, H&E staining showed less pyramidal cells in the hippocampus, with disorganized layers, karyopyknosis, decreased endochylema, and cavitation, effects relieved in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. Troxerutin alleviates oxidative stress and promotes learning in streptozotocin-induced T1DM rats, a process involving GCLC expression.

Topics: Animals; Cognition Disorders; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Drug Evaluation, Preclinical; Glutamate-Cysteine Ligase; Hippocampus; Hydroxyethylrutoside; Hypoglycemic Agents; Male; Maze Learning; Nootropic Agents; Oxidative Stress; Random Allocation; Rats, Sprague-Dawley; Thioctic Acid

There is increasing evidence that essential tremor (ET) is a complex and heterogeneous disorder with nonmotor features including cognitive deficits and sleep problems. We are unaware of a study that has examined sleep deficits in ET across the full spectrum of cognitive presentations. Cross-sectional (baseline) data on self-reported nighttime sleep dysfunction and excessive daytime sleepiness were collected using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) in 96 ET cases enrolled in a prospective study. Cases underwent a comprehensive neuropsychological assessment, and were classified as ET with normal cognition (ET-NC), ET with mild cognitive impairment (ET-MCI), and ET with dementia (ET-D). PSQI scores did not significantly differ across the three ET cognitive groups (p=0.22). ESS scores were highest (more daytime sleepiness) in the ET-MCI group, followed by the ET-D and ET-NC groups, respectively (p=0.016). We examined sleep dysfunction across the cognitive spectrum in ET. We demonstrate for the first time that excessive daytime sleepiness is greater in ET-MCI than ET-NC. Unpredicted low ESS scores in the dementia group raises two possibilities: a self-report bias related to cognitive impairment and/or the possibility that currently undefined pathological heterogeneity in ET may map onto multiple presentations of non-motor deficits.

Topics: Aged; Aged, 80 and over; Cognition; Cognition Disorders; Cross-Sectional Studies; Dementia; Essential Tremor; Female; Humans; Hydroxyethylrutoside; Male; Neuropsychological Tests; Self Report; Sleep; Sleep Wake Disorders

Recent findings suggest that neurotoxicity is the mechanism underlying the induction of neuronal insulin resistance by a high cholesterol diet. Troxerutin, a naturally occurring flavonoid, has been reported to possess biological activity beneficial to human health. Our recent studies have demonstrated that troxerutin attenuates cognitive impairment and oxidative stress induced by D-galactose in mouse brain through decreasing advanced glycation end products, reactive oxygen species and protein carbonyl levels and enhancing phosphoinositide 3-kinase/Akt activation. In this study, we evaluated the effect of troxerutin on cognitive impairment induced by brain insulin resistance in mice fed a high-cholesterol diet, and explored its potential mechanism. Our results showed that oral administration of troxerutin to these mice significantly improved behavioural performance in a step-through passive avoidance task and a Morris water maze task, at least in part, by decreasing the levels of reactive oxygen species, protein carbonyl and advanced glycation end products and blocking endoplasmic reticulum stress via reduced phosphorylation of the pancreatic endoplasmic reticulum-resident kinase and eukaryotic translation initiation factor 2α. Furthermore, troxerutin significantly inhibited the activation of c-jun N-terminal kinase 1 and IκB kinase β/nuclear factor-κB induced by endoplasmic reticulum stress and enhanced insulin signalling pathway, which prevented obesity, restored normal levels of blood glucose, fatty acids and cholesterol and increased the phosphorylation of cyclic adenosine monophosphate response element-binding protein and the expression levels of c-fos in the hippocampus. Moreover, troxerutin significantly inhibited endoplasmic reticulum stress-induced apoptosis and decreased the activation of caspase-12 and caspase-3, and reduced the mean optical density of the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end label-positive cells in the hippocampus. However, intra-cerebroventricular infusion of PI-103, a specific phosphoinositide 3-kinase 110α inhibitor, significantly inhibited the expression levels of phosphoinositide 3-kinase 110α and phosphoinositide 3-kinase downstream signalling in the hippocampus of mice co-treated with high cholesterol and troxerutin and vehicle control mice. These results suggest that troxerutin could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in typ

Topics: Animals; Avoidance Learning; Blood Glucose; Body Weight; Brain; Cholesterol; Cognition Disorders; CREB-Binding Protein; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Fatty Acids, Nonesterified; Gene Expression Regulation; Glycation End Products, Advanced; Hydroxyethylrutoside; Immunoprecipitation; In Situ Nick-End Labeling; Infusions, Intraventricular; Insulin Resistance; Male; Maze Learning; Mice; Mice, Inbred C57BL; Neuroprostanes; Phosphorylation; Protein Carbonylation; Reactive Oxygen Species; Signal Transduction; Triglycerides

D-galactose-(D-gal)-treated mouse, with cognitive impairment, has been used for neurotoxicity investigation and anti-neurotoxicity pharmacology research. In this study, we investigated the mechanism underlying the neuroprotective effect of troxerutin. The results showed that troxerutin improved behavioral performance in D-gal-treated mice by elevating Cu, Zn-superoxide dismutases (Cu, Zn-SOD) activity and decreasing reactive oxygen species levels. Furthermore, our results showed that troxerutin significantly promoted nerve growth factor (NGF) mRNA expression which resulted in TrkA activation. On one hand, NGF/TrkA induced activation of Akt and ERK1/2, which led to neuronal survival; on the other hand, NGF/TrkA mediated CaMKII and CREB phosphorylation and increased PSD95 expression, which improved cognitive performance. However, the neuroprotective effect of troxerutin was blocked by treatment with K252a, an antagonist for TrkA. No neurotoxicity was observed in mice treated with K252a or troxerutin alone. In conclusion, administration of troxerutin to D-gal-injected mice attenuated cognitive impairment and brain oxidative stress through the activation of NGF/TrkA signaling pathway.

Topics: Analysis of Variance; Animals; Avoidance Learning; Behavior, Animal; Brain; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Carbazoles; Cognition Disorders; CREB-Binding Protein; Disease Models, Animal; Disks Large Homolog 4 Protein; Enzyme Inhibitors; Galactose; Gene Expression Regulation; Guanylate Kinases; Hydroxyethylrutoside; Indole Alkaloids; Intracellular Signaling Peptides and Proteins; Male; Maze Learning; Membrane Proteins; Mice; Nerve Growth Factor; Neuroprotective Agents; Reactive Oxygen Species; Receptor, trkA; Signal Transduction; Superoxide Dismutase