Therapeutic effects of saffron extract on different memory types, anxiety, and hippocampal BDNF and TNF-α gene expressions in sub-chronically stressed rats.

Objective: While stress reportedly impairs memory, saffron enhances it. This study investigated the therapeutic effects of saffron extract on different memory types, anxiety-like behavior, and expressions of BDNF and TNF-α genes in sub-chronically stressed rats.Methods: Rats were randomly assigned to control, restraint stress (6 h/day/7 days), two 7-days saffron treatments with 30 and 60 mg/kg, and two stress-saffron groups (30 and 60 mg/kg/7 post-stress days). Serum cortisol level and hippocampal BDNF and TNF-α gene expressions were measured. Open field, passive avoidance, novel object recognition, and object location tests were performed to assess anxiety-like behavior and avoidance as well as cognitive and spatial memories, respectively.Results: The low saffron dose in the sub-chronic stressed group led to a significant increase in passive avoidance latency from day 3 onward whereas this effect was observed after 7 days under the high-dose treatment that simultaneously led to a significant decline in serum cortisol level. While the low saffron dose led to a sharp drop in hippocampal TNF-α gene expression, the high dose significantly increased the hippocampal BDNF gene expression in the sub-chronic stress group. Finally, both saffron doses reduced anxiety in the stressed groups.Conclusion: Compared to the low saffron dose, the high dose had a latent but long-lasting impact. Cognitive and spatial memories remained unaffected by either stress or saffron treatment. In addition, only the high saffron dose reversed anxiety in the sub-chronically stressed group. These findings suggest that various doses of saffron act differently on different brain functions under sub-chronic stress conditions.Abbreviations: Brain derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), hypothalamic-pituitary-adrenal axis (HPA), novel object recognition task (NORT), novel object location task (NOLT), open field test (OFT), passive avoidance (PA).

Possible involvement of the dopamine D2 receptors of ventromedial hypothalamus in the control of free- and scheduled-feeding and plasma ghrelin level in rat.

OBJECTIVES: We investigated effect of the ventromedial hypothalamus (VMH) dopamine D2 receptor inhibition on food intake and plasma ghrelin following chronic free or scheduled meal with different caloric intakes. METHODS: Male Wistar rats (220-250 g) were fed diets containing free (control) or three scheduled diets of standard, restricted and high-fat for 1 month. The animals stereotaxically received an intra VMH single dose of sulpiride (0.005 µg)/or saline (0.5 µL) before meal time. Thirty minutes later, food intake and circulating ghrelin were measured. RESULTS: Sulpiride significantly reduced food intake and ghrelin concentration in freely fed and scheduled-standard diet (p<0.05), while increased food intake, with ghrelin level on fasted level in scheduled-restricted group (p<0.01) compared to control. Food intake and ghrelin concentration between scheduled-high fat and freely fed or scheduled-standard diets did not show significant changes. CONCLUSIONS: The VMH D2 receptors are possibly involved in controlling scheduled eating behavior, depending on energy balance context.

The effects of concurrent treatment of silymarin and lactulose on memory changes in cirrhotic male rats.

Introduction: Chronic liver disease frequently accompanied by hepatic encephalopathy (HE). Changes in the permeability of the blood-brain barrier in HE, make an easier entrance of ammonia among other substances to the brain, which leads to neurotransmitter disturbances. Lactulose (LAC), causes better defecation and makes ammonia outreach of blood. Silymarin (SM) is a known standard drug for liver illnesses. The purpose of this research was to determine the results of LAC and SM combined treatment, on the changes in memory of cirrhotic male rats. Methods: The cirrhotic model established by treatment with thioacetamide (TAA) for 18 weeks. Cirrhotic rats randomized to four groups (n = 7): TAA group (received drinking water), LAC group (2 g/kg/d LAC in drinking water), SM group (50 mg/kg/d SM by food), SM+ LAC group (similar combined doses of both compounds) for 8 weeks. The control group received drinking water. The behavior examined by wire hanging (WH), passive avoidance (PA), and open field (OF) tests. Results: Our findings showed that treatment with SM+LAC effectively increased PA latency, compared with the control group. The results showed that the administration of LAC and SM+LAC affected the number of lines crossed, the total distance moved and velocity in the OF tests. Conclusion: SM and LAC have anti-inflammatory effects that are memory changing. It may be due to their useful effects. These results indicated that SM+LAC restored memory disturbance and irritated mood in the cirrhotic rats. Comparable neuroprotection was never previously informed. Such outcomes are extremely promising and indicate the further study of SM+LAC.

Stress biomarker responses to different protocols of forced exercise in chronically stressed rats.

Stress is one of the most significant causes of major health problems on a global scale. The beneficial effects of exercise on combating stress, however, are well-established. The present study investigated the stress biomarker responses, such as serum corticosterone, interlukin-1ß, and glucose levels, to different (preventive, therapeutic, protective, and continuous) protocols of forced exercise under stress. Male rats were randomly allocated to the following five groups: stressed, preventive, therapeutic, protective, and continuous (and/or pre-stress, post-stress, stress-accompanied, and both pre-stress and stress-accompanied exercise respectively) exercise groups. Stress was applied 6 h/day for 21 days and the treadmill running was employed at a speed of 20-21 m/min for 21 and 42 days. The findings showed that the therapeutic, protective, and continuous exercises led to reduced corticosterone and glucose levels. Whereas, the preventive exercise did not reverse the stress responses, and that the therapeutic exercise led to a significant decline in serum interlukin-1ß. It is concluded that protective, therapeutic, and, particularly, continuous exercises lead to significant reductions in serum corticosterone and the associated stress-induced hyperglycemia. Moreover, it appears that the timing and duration of exercise are the two factors contributing to changes in stress biomarker responses.

Preventive and therapeutic effect of treadmill running on chronic stress-induced memory deficit in rats.

Previous results indicated that stress impairs learning and memory. In this research, the effects of preventive, therapeutic and regular continually running activity on chronic stress-induced memory deficit in rats were investigated. 70 male rats were randomly divided into seven groups as follows: Control, Sham, Stress-Rest, Rest-Stress, Stress-Exercise, Exercise-Stress and Exercise-Stress & Exercise groups. Chronic restraint stress was applied 6 h/day for 21days and treadmill running 1 h/day. Memory function was evaluated by the passive avoidance test. The results revealed that running activities had therapeutic effect on mid and long-term memory deficit and preventive effects on short and mid-term memory deficit in stressed rats. Regular continually running activity improved mid and long-term memory compared to Exercise-Stress group. The beneficial effects of exercise were time-dependent in stress conditions. Finally, data corresponded to the possibility that treadmill running had a more important role on treatment rather than on prevention on memory impairment induced by stress.

The effect of treadmill running on memory before and after the NBM-lesion in rats.

Some studies have shown the effects of exercise training in retarding onset and progression of memory deficit in neurodegenerative disorders such as Alzheimer's disease. In this research, we investigated the effect of treadmill running on memory function; before, after, and continually (before and after) the nucleus basalis magnocellularis lesions. 66 male rats were randomly divided into six groups, including control, sham operation, the NBM-lesion, exercise before the NBM-lesion, exercise after the NBM-lesion, and exercise before and after the NBM-lesion. Lesion was induced by 5 µg/µl bilateral injection of Ibotenic acid. Memory function was assessed by using the passive avoidance learning test. Our results showed that treadmill running delays cognitive decline in the NBM-lesion rats, prevented memory deficit, and has advantageous effects on short-term, intermediate and long-term memory. Exercising on a regular basis may impede memory loss significantly, which may be attributed to specific molecular pathways in the brain.