Dental Pulp Stem Cells Transplantation Improves Passive Avoidance Memory and Neuroinflammation in Trimethyltin-Induced Alzheimer’s Disease Rat Model

Background: According to the increasing incidence of Alzheimer’s disease (AD), this study aimed to investigate the effect of dental pulp stem cells (DPSCs) transplantation on passive avoidance memory and neuroinflammation in trimethyltin (TMT)-induced AD rat model. Materials and Methods: In this experimental study, 18 male Wistar rats were randomly divided into three groups: the control that rats received 8 mg/kg TMT plus 0.5 ml phosphate buffered saline (PBS) and TMT+DPSCs (TMT + 1×106 cells/ml DPSC in 0.5 ml PBS) groups. Then, after one month, passive avoidance test was performed. Also measured the Nuclear Factor Kappa-β (NF-Kβ) serum level and the percentage of damaged neurons in the hippocampus were determined. Results: DPSCs transplantation showed significantly increased step-through latency to the dark compartment in comparison with control and TMT+PBS groups in 24 hours after shock. Also, time spent in the dark compartment of TMT+DPSCs significantly decreased compared to control and TMT+PBS groups in 24 and 48 hours after shock (P<0.05). Furthermore, DPSCs transplantation significantly decreased the NF-Kβ serum level and percentage of damaged pyramidal neurons of CA1 compared with TMT+PBS (P<0.05). Conclusion: DPSCs transplantation improved memory and learning, regulated NF-Kβ serum level, and decreased damage neurons of CA1 hippocampus in TMT-induced AD rat model.

Effects of different dark chocolate diets on memory functions and brain corticosterone levels in rats under chronic stress

Introduction: Stress influences cognitive behavior adversely, whereas dark chocolate exhibits positive effects on memory processes. This study investigated the effects of different dark chocolate diets on various aspects of brain functions in rats under chronic stress Methods: Thirty-five rats were randomly allocated into five groups: control, stress, stress with different (compulsory, optional and restricted) dark chocolate diets. Latency, dark stay (DS) time and the number of entrance to the dark compartment were respectively evaluated as memory, memory consolidation and locomotor activity by passive avoidance test. Results: There were significant differences between initial latency and latency after 1 day in all groups. In the stress-compulsory and restricted dark chocolate diet groups, latency after 1 day increased significantly. Moreover, the DS time was not significantly higher in the stressed group than the control group. The DS time and number of entrance to dark compartment decreased significantly in the stress-compulsory dark chocolate diet group compared to the stressed group. Furthermore, the number of entrance to dark compartment was significantly higher for the stress- optional dark chocolate diet compared to those with the compulsory diet. Additionally, serum and hippocampal corticosterone levels, except in the frontal cortex, were significantly lower only in the stress-compulsory dark chocolate diet group compared to the stressed group. Conclusion: Different dark chocolate diets had various effects on brain functions under chronic stress. Respectively, the compulsory and optional dark chocolate diets had the best and least effects on brain function improvement. Only the compulsory dark chocolate diet could improve brain functions such as memory, memory consolidation and locomotor activity.

GLP-1 receptor agonists have a sustained stimulatory effect on corticosterone release after chronic treatment

ObjectiveGlucagon-like peptide 1 (GLP-1) receptor agonists are a new group of antidiabetic medications quickly gaining popularity. We aimed to examine behavioural and neuroendocrine changes following chronic treatment with GLP-1 receptor agonists in animal models.MethodsThe effects of chronic treatment with GLP-1 receptor agonists were determined on behavioural parameters [anxiety level in the light–dark compartment test, the motor activity in automated activity cages, immobility in the forced swimming test (FST)] and on corticosterone release in mice. The possible antidepressant effect of chronic liraglutide treatment was also studied in Flinders Sensitive Line (FSL) rats, a genetic model of depression.ResultsTwo weeks of treatment with exenatide (10 µg /kg twice daily) or liraglutide (1200 µg/kg once daily) did not affect the anxiety level in a light–dark compartment test nor induce an antidepressant-like effect in the FST in mice. Moreover, chronic treatment with liraglutide had no effect on depression-related behaviour in FSL rats. Interestingly, hypolocomotion induced by the drugs in mice disappeared after chronic dosing. Both of the GLP-1 receptor agonists induced robust increases in corticosterone levels in mice under basal conditions as well as in the case of combination with swimming stress. Remarkably, exenatide was as potent a stimulator of corticosterone release after 2 weeks as after acute administration.ConclusionsThe increases in corticosterone release seen after acute exenatide or liraglutide treatment do not abate after 2 weeks of treatment demonstrating that tolerance does not develop towards this particular effect of GLP-1 agonists.

Rat aversion to isoflurane versus carbon dioxide

Some experts suggest that sedation of laboratory rodents with isoflurane before euthanasia with carbon dioxide (CO 2 ) is a humane alternative to euthanasia with CO 2 alone, but little research has compared aversion with these agents. Albino rats were tested in a light–dark box where they had the choice between remaining in a dark compartment filling with isoflurane or CO 2 , or escaping to a lit compartment. Experiment 1 validated the procedure by confirming that rats responded to agent and light intensity. In experiment 2, 9/16 and 0/16 rats remained in the dark compartment until recumbent when initially exposed to isoflurane and CO 2 , respectively. In experiment 3, more rats remained in the dark compartment until recumbent during initial (10/16) versus re-exposure (1/16) to isoflurane. These results indicate that initial exposure to CO 2 is more aversive than isoflurane, and that re-exposure to isoflurane is more aversive than initial exposure. We conclude that sedation with isoflurane is a refinement over euthanasia with CO 2 alone for rats that have not been previously exposed to inhalant anaesthetics.

Effect of Aqueous Extract ofCrocus sativusL. on Morphine-Induced Memory Impairment

In the present study, the effect of aqueous extracts of saffron on morphine-induced memory impairment was investigated. On the training trial, the mice received an electric shock when the animals were entered into the dark compartment. Twenty-four and forty-eight hours later, the time latency for entering the dark compartment was recorded and defined as the retention trial. The mice were divided into (1) control, (2) morphine which received morphine before the training in the passive avoidance test, (3–5) three groups treated by 50, 150 and 450 mg/kg of saffron extract before the training trial, and (6 and 7) the two other groups received 150 and 450 mg/kg of saffron extract before the retention trial. The time latency in morphine-treated group was lower than control (P< 0.01). Treatment of the animals by 150 and 450 mg/kg of saffron extract before the training trial increased the time latency at 24 and 48 hours after the training trial (P< 0.05 andP< 0.01). Administration of both 150 and 450 mg/kg doses of the extract before retention trials also increased the time latency (P< 0.01). The results revealed that the saffron extract attenuated morphine-induced memory impairment.

Propofol Enhances Memory Formation via an Interaction with the Endocannabinoid System

Background Propofol is associated with postoperative mood alterations and induces a higher incidence of dreaming compared with other general anesthetics. These effects might be mediated by propofol's inhibitory action on fatty acid amide hydrolase, the enzyme that degrades the endocannabinoid anandamide. Because propofol is also associated with a higher incidence of traumatic memories from perioperative awareness and intensive care unit treatment and the endocannabinoid system is involved in regulating memory consolidation of emotional experiences, the authors investigated whether propofol, at anesthetic doses, modulates memory consolidation via an activation of the endocannabinoid system. Methods Male Sprague-Dawley rats were trained on an inhibitory avoidance task in which they received an inescapable foot shock upon entering the dark compartment of the apparatus. Drugs were administered intraperitoneally immediately or 30, 90, or 180 min after training. On the retention test 48 h later, the latency to reenter the dark compartment was recorded and taken as a measure of memory retention. Results The anesthetic doses of propofol administered after training significantly increased latencies of 48-h inhibitory avoidance performance (483.4 ± 181.3, 432.89 ± 214.06, 300 and 350 mg/kg, respectively; mean ± SD) compared with the corresponding vehicle group (325.33 ± 221.22, mean ± SD), which is indicative of stronger memory consolidation in propofol treated rats. Administration of a nonimpairing dose of the cannabinoid receptor antagonist rimonabant blocked the memory enhancement induced by propofol (123.39 ± 133.10, mean ± SD). Delayed administration of propofol 90 and 180 min after training or immediate posttraining administration of the benzodiazepine midazolam or the barbiturate pentobarbital did not significantly alter retention. Conclusions These findings indicate that propofol, in contrast to other commonly used sedatives, enhances emotional memory consolidation when administered immediately after a stressful event by enhancing endocannabinoid signaling.