Impact of enriched environment on production of tau, amyloid precursor protein and, amyloid-ß peptide in high-fat and high-sucrose-fed rats.

OBJECTIVE: The Western-type diet is associated with an elevated risk of Alzheimer's disease and other milder forms of cognitive impairment. The aim of the present study was to investigate the effects of the environmental enrichment on amyloid and tau pathology in high-fat and high-sucrose-fed rats. METHODS: In total, 40 adult male rats were categorised into two main groups according to their housing conditions: enriched environment (EE, n=16) and standard housing condition (n=24). The groups were further divided into five subgroups that received standard diet, high-fat diet, and high-sucrose diet. We performed the analysis of amyloid ß-peptide (Aß) (1-40), Aß(1-42), amyloid precursor protein (APP), and tau levels in the hippocampus of rats that were maintained under standard housing conditions or exposed to an EE. RESULTS: The EE decreased the Aß(1-40), Aß(1-42), APP, and tau levels in high-fat and high-sucrose-fed rats. CONCLUSION: This observation shows that EE may rescue diet-induced amyloid and tau pathology.

Environmental enrichment reverses cognitive impairments provoked by Western diet in rats: Role of corticosteroid receptors.

AIMS: Previous studies demonstrated that the Western diet (WD), which is rich in saturated fat (HFD) and refined sugar (HSU), is related to the impairments of hippocampus-dependent learning and memory and forebrain synaptic plasticity in rodents. The environmental enrichment (EE) has been shown to enhance learning and memory in the HFD-induced cognitive deficits, but the exact mechanism is still not clearly understood. Therefore, the present study aimed to clarify the effects of the EE on spatial memory in WD-fed rats, and to analyze the potential role of corticosteroid receptors in the EE conditioning. MAIN METHODS: Male Wistar albino rats were housed in either an enriched or standard environment and fed with the HFD (35% of energy as fat), HSU (100% of carbohydrate as sucrose) or standard rat chow for 4weeks. We used the Morris' water maze test (MWM) to assess the learning and memory performance, and measured plasma levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH), as well as glucocorticoid (GR) and mineralocorticoid receptor (MR) levels in the hippocampus. KEY FINDINGS: The results showed that HFD-fed rats displayed poorer learning and memory performance evaluated with MWM than controls. The EE reversed the cognitive deficits caused by the HFD. In addition, the EE resulted in an increase of GR and MR levels without affecting plasma CORT and ACTH concentrations. SIGNIFICANCE: Based on these findings, it could be suggested that the EE plays an important role in amelioration of the HFD-induced cognitive impairments, but this intervention is independent of the hypothalamic-pituitary-adrenal axis and hippocampal corticosteroid receptor levels.

Curcumin improves spatial memory and decreases oxidative damage in aged female rats.

Aging induced cognitive impairment has been well documented for many years and several antioxidant strategies have been developed against this impairment. Curcumin is the active component of curcuma longa and has shown antioxidant, antiinflamatory and neuroprotective properties. We hypothesized that curcumin would have an influence on cognitive functions in aged female rats. The purpose of the present study was to investigate the effects of curcumin supplementation on cognitive impairment evaluated by Morris water maze (MWM) as well as the oxidative stress induced by aging in female rats. Rats were randomly divided into either control or curcumin-supplemented groups. Curcumin or vehicle (corn oil) were given once daily for a period of 12 days, beginning 7 days prior to and 5 days during the behavioral tests. Behavioral assessment was performed in MWM. At the end of the behavioral test, blood samples and brain tissues were taken for the analysis of malondialdeyde (MDA), protein carbonyl and glutathione levels. During the training session, curcumin supplementation decreased latency to reach to the platform and the total distance traveled. During the probe trial, curcumin supplementation increased the number of platform crossings. In addition to the behavioral testing, biochemical results showed that MDA levels decreased in brain tissue by curcumin supplementation. It may be concluded that, curcumin supplementation improves cognitive functions by decreasing the lipid peroxidation in brain tissue of aged female rats.

Role of calcium in contractile responses of calf cardiac vein during cooling.

The effects of cooling (to 28 °C) were studied on the responses induced by carbachol (10(-9) - 3 × 10(-4) M) and serotonin (5-HT, 10(-8) - 3 × 10(-4) M) in calf cardiac vein preparations and the role of calcium ions in these effects were analyzed. Ring preparations of veins obtained from calf hearts were suspended in organ baths containing 25 mL of Krebs-Henseleit solution, maintained at 37 °C and continuously gassed with 95%O(2)-5%CO(2). After a resting period, preparations were contracted with carbachol (10(-9) - 3 times; 10(-4) M) and 5-HT (10(-8) - 3 times; 10(-4) M) at 37 °C. The same protocol was repeated at 28 °C after the preparations were allowed to equilibrate at this temperature for 60 min. In order to analyze the role of calcium ions (Ca(2+)) in the cooling-induced vascular response, concentration-response curves to carbachol and 5-HT were obtained in the presence of verapamil (10(-6) M), caffeine (3 times; 10(-4) M), and Ca(2+ )free medium in the presence of EGTA at 28 °C. During cooling to 28 °C, the EC(50) values, to carbachol and 5-HT were significantly higher than at 37 °C. Cooling to 28 °C in the presence of verapamil, caffeine or Ca(2+ )free medium in the presence of EGTA increased the EC(50) values, to both carbachol and 5-HT. These results suggest that Ca(2+) plays an essential role in the cooling-induced changes of calf cardiac vein preparations treated with carbachol and 5-HT.

Diabetes mellitus- and cooling-induced bladder contraction: an in vitro study.

The effects of diabetes mellitus during cooling on ACh- and KCl-induced responses were investigated in rat urinary bladder. Diabetes was induced in the rats by 50 mg/kg streptozotocin via an intraperitoneal injection. Rats' body and bladder weights were measured. The isometric tension to ACh (10(-9) - 3 × 10(-4) M) and KCl (5-100 mM) in strips of urinary detrusor muscle of diabetic and non-diabetic rats, in organ baths at 37 and 28ºC were recorded. The body weights were significantly decreased and the bladder weights increased in STZ-induced diabetic group compared to the non-diabetic group. ACh and KCl caused concentration-dependent contractions of urinary bladders from non-diabetic and STZ-induced diabetic rats. During cooling, the sensitivity and the maximal response were significantly higher than those during 37ºC, both in non-diabetic and diabetic preparations. Cooling of detrusor muscle preparations induces a graded contraction inversely proportional to the temperature in diabetic rats. It may be assumed that the cooling response involves the same mechanisms in the diabetic and non-diabetic animals.

Cooling and response to hydrogen peroxide in human saphenous vein: role of the endothelium.

In the present work we studied the responses of human saphenous vein to H2O2 and effects of moderate cooling on these responses with analysis of the role of endothelium. H2O2 (10(-7)-10(-2) M) induced concentration-dependent contraction in the intact human saphenous vein strips at both temperatures. At 28 degrees C, the maximal contraction induced by H2O2 was significantly lower than that at 37 degrees C. Compared with intact strips, the sensitivity and the maximal contraction to H2O2 were significantly enhanced in endothelium-denuded strips at 37 and 28 degrees C. However, pD2 values and maximal contractions were not significantly different in endothelium-denuded strips at different temperatures. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) increased significantly the maximal contraction and sensitivity to H2O2 at 37 and 28 degrees C. The contractions increased by L-NAME were restored by the pre-incubation of l-arginine (10(-3) M) at every temperature studied. The contractile responses of intact human saphenous veins to H2O2 were reduced significantly by 10(-5) M indomethacin at both temperatures. Our results suggest that H2O2-induced contraction of human saphenous vein are mediated by its direct effect on the smooth muscle and by the generation of products of the cyclooxygenase pathway from the endothelium. Signalling pathways of these contractile effects are the same at 37 and 28 degrees C. Under normal temperature conditions, the contraction to H2O2 is possibly modulated by endothelial nitric oxide. Cooling reduces the contraction to H2O2 by increasing release of nitric oxide.