Physiology and Pharmacology
Volume:13 Issue: 3, 2009

Psychotropic drugs exert their effects, in part, by increasing neurotrophin levels in the brain. Nerve growth factor (NGF) protein levels after treatment with only a limited number of psychotropics have been determined. The present study was designed in order to evaluate the effects of acute and chronic administration of different psychotropic drugs on NGF protein levels in five brain regions including frontal cortex, hippocampus, amygdala, olfactory bulb, and brain stem. Adult male Sprague-Dawley rats received acute or chronic (21 days) injections of desipramine, phenelzine, fluoxetine, chlordiazepoxide (10 mg/kg, each), haloperidol (1 mg/kg), and clozapine (20 mg/kg). Twentyfour hours after the last injection, NGF protein level was quantified in the dissected brain regions by using an ELISA kit. Acute administration of these drugs did not affect NGF protein levels in the brain. Chronic injections of desipramine, phenelzine, fluoxetine, haloperidol, and clozapine led to the enhancement of NGF in the frontal cortex. Desipramine, fluoxetine, phenelzine and clozapine enhanced NGF in the hippocampus. In the olfactory bulb, desipramine and fluoxetine increased NGF, whereas, phenelzine and haloperidol reduced it. NGF levels in the amygdala and brain stem were not changed by any medication. Chronic administration of chlordiazepoxide did not affect NGF protein in the brain. Psychotropic drugs exert dissimilar effects on NGF protein levels in the brain. This might be indicative of their therapeutic properties and differential effects on cognitive function.

Liver ischemia/reperfusion (IR) is a major clinical problem, which occurs during several conditions such as liver damage, trauma and transplantation. Recent studies indicate that IR-induced acute liver failure causes injuries of distant organs such as heart and lungs by systematic inflammatory responses. Therefore, in the present study, effects of hepatic IR induction were studied on the kidneys. Male rats were subjected to either sham operation or 90 min liver ischemia followed by 4 or 24 hrs of reperfusion. Liver IR injury was assessed by measurement of serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenases (LDH) levels. Blood Urea Nitrogen (BUN) and creatinine (Cr) were determined as renal function indices. Renal malondialdehyde (MDA), superoxide dismutase (SOD) and catalase activities were also evaluated for assessment of oxidative stress. Ninety min liver ischemia followed by 4 hours of reperfusion caused a reduction in renal function demonstrated by an increase in BUN level. This was accompanied by an increase in renal MDA levels and a decrease in SOD and catalase activities. Liver reperfusion for 24 hours resulted in smaller damage to renal function and oxidative stress parameters. This study suggests that liver IR causes renal damage reflected in functional abnormalities and oxidative stress. This damage is reduced by increasing the reperfusion time.

The Serum/Glucose deprivation -induced cell death in cultured PC12 cells represents a useful in vitro model for the study of brain ischemia and neurodegenerative disorders. Nigella sativa L. has been known as a source of antioxidants. To elucidate the neuroprotective actions of N. sativa extract in vitro, we studied the effect of N. sativa extract on cultured PC12 cells under serum/glucose deprivation conditions. PC12 cells were cultured in DMEM medium containing 10% (v/v) fetal bovine serum, 100 units/ml penicillin, and 100 μg/ml streptomycin. Cells were seeded overnight and then deprived of serum/glucose for 6 and 18 h. Cells were pretreated with different concentrations of N. sativa extract (7.81-250 μg/ml). Cell viability was quantitated by MTT assay. Intracellular ROS production was measured by flow cytometry using 2', 7’-Dichlorofluorescin diacetate (DCF-DA). Depriving the PC-12 cells of serum/glucose caused prominent cell toxicity at least after 6 and 18 h. Pretreatment of PC12 cells with N. sativa (7.81-250 μg/ml) could reduce serum/glucose deprivation-induced cytotoicity in PC12 cells after 18 h. The experimental results suggest that N. sativa extract protects the PC12 cells against Serum/Glucose deprivation-induced cytotoxicity. Our findings might raise a possibility of potential therapeutic application of N. sativa extract for preventing and treating cerebral ischemic and neurodegenerative diseases.

Visual system have been considered as among important sensory system in animals’ life span and their survival is closely related to normal visual system functioning. Since in previous studies it have been revealed that morphine consumption during pregnancy could lead to defect and delay in nervous system development in the embryos, in the present study, changes induced by morphine in Fovea area in the ayes of embryos whom their mothers received oral morphine during pregnancy period were studied. Female Wistar rats (250-300 g) were used in this study. 24 hours after mating with male rats, the females were separated and their vaginal smear was obtained for sperm detection. This day was considered as embryonic day zero (E0). The females then were divided randomly into experimental or control group. Controls received tap water where as experiments received morphine (0.05 mg/ml) in their waters. On the E13 blood samples were collected from the retro-orbital sinus of all animals for plasma corticosterone detection. On the E17, the animals were killed by chloroform over dose and their embryos were taken out surgically. The embryos were fixed in formalin 10% for 30 days. Their length and weight were determined by digital scale and kalper respectively. At this time, the embryos head was removed for tissue processing, cutting and Hematoxylin -Eosin (H&E) staining. The samples were evaluated using light microscope and MOTIC soft ware. Our data indicated that plasma corticosterone level was dramatically increased in experimental group. Interestingly, neither weight nor the length of the embryos did not statistically differ in experimental compare with controls. In addition, the Fovea area was thinner in experimental group and there was space between cells. This results indicated that oral morphine consumption during pregnancy may induces defect or delay in Fovea development and at least a part of this defect may be due to an increase in plasma corticosterone level in experimental group. Keywords: Visual System, Fovea, Morphine, Corticosterone, Rat. *Corresponding

Ruta graveolens (RG) stimulates muscles of the uterus, which in turn may initiate menstrual cycles. RG decreases fertility and may also block the implantation of a fertilized egg. This work was undertaken to examine the possible effect of aqueous extract of RG on the reproductive system of immature female mice. For this reason, immature female Balb/C mouse aged 4-5 weeks were allocated to experimental, vehicle and control groups. After the determination of the LD50 of RG, which was 620 mg/kg, animals in experimental group were given 310 mg/kg of the aqueous extract of RG by intraperitoneal injections every other day for one week. In the vehicle group, animals received similar amounts of normal saline and the animals in the control group received no treatment. One month after the last injection, animals were deeply anaesthetized and blood was collected by cardiac puncture. Serum was separated and kept at -20°C. Ovaries were also removed at the same time, weighed and kept in Bouin's solution for histological analysis. The results showed a significant decrease (p<0.01) in the number of primordial follicles in the experimental group compared to the group of control. Also the ovarian weight, number of corpus luteum and the diameter of remaining corpus luteum decreased. The reduction of the diameter of corpus luteum was significant (p<0.05) compared to the control animals. The number of atretic graffian follicles was significantly increased (p<0.05), while estrogen levels were significantly decreased (p<0.05) in the experimental group compared to the control. Aqueous extract of RG can interfere with reproductive system function in immature female mice by alterations in sex hormonal level and ovarian morphology and might be useful as an antifertility substance.

Gama amino butyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian nervous system. The concentration of GABA and the number of GABA cell secretion decrease in diabetic patient and experimental diabetes model. The reported effects of GABA activation on insulin secretion from beta cells have been controversial. In this study we investigated if GABA administration in animal diabetes model can change insulin and glucagon secretion and improve some diabetic symptoms. Twenty fourth-week old NOD mi(Non obese diabetic mice) ce were used. Two months after diabetic induction animals were divided into the two groups. One group received 200 μmol of GABA and the other group received phosphate buffer solution (PBS) for one month. GABA administration could significantly decrease plasma glucose and glucagon level, water consumption and urine volume and body fat distribution in the mesenteric bed and abdominal wall. It also could increase plasma Cpeptide level and it has not effect on food intake. NOD mice is very good genetically model for type one diabetes and GABA administration in this mice could treatment some of diabetic symptom. It seems may be we could use of GABA for treatment of diabetic symptom in future.

Diabetes mellitus has adverse effects on male sexual and reproductive functions in human and animals. Diabetes results in reduced fertility and libido. Medicinal plants have attracted much attention in controlling many diseases such as diabetes. In the present study, we aimed to investigate the effect of garlic juice on testicular damage. Forty male rats (250±20) were divided into 5 groups as follows: 1- Group normal (N) 2- Group Normal+Garlic (N+G) received garlic juice for 6 weeks. 3- Diabetic (D) received streptozotocin (STZ), 60mg/kg BW/i.p. 4- Group diabetic+garlic before (D+Gb) received garlic juice for 3 weeks before STZ injection and continued for more 3 weeks. 5- Group diabetic+garlic after (D+Ga) three days after STZ injection, they received garlic juice for 3 weeks. Garlic juice was given by gavage (1ml/100g BW). Number of leydig cells, testis weight, serum levels of testosterone and estradiol were assessed. diabetic rats showed a marked decrease in the number of leydig cells, testis weight, serum levels of testosterone and estradiol. Garlic juice significantly increased the number of leydig cells, testis weight, serum levels of testosterone and estradiol in group 4 and 5 compared to group 3. The diabetic group receiving garlic before STZ injection showed more amelioration in complications than that receiving it after STZ injection. these results suggest that garlic juice supplementation could play both preventive and therapeutic role on testicular damage in diabetic rats.

This study presents a computerized analyzing method for detection of instantaneous changes of far and near walls of the common carotid artery in sequential ultrasound images by applying the maximum gradient algorithm. Maximum gradient was modified and some characteristics were added from the dynamic programming algorithm for our applications. The algorithm was evaluated on the common carotid artery of 10 healthy volunteers. Local measurements of vessel intensity, intensity gradient and boundary continuity are extracted for all of the sequential ultrasonic frames throughout three cycles. We extracted the instantaneous changes of far and near arterial walls and hence the lumen diameter. The manual measurements were applied and compared for validation of the automatic method. Peak systolic, end diastolic and mean diameters extracted by the automated method were compared with the same parameters measured by the manual method throughout three cycles. There was no significant difference between automated and manual methods (p>0.05) with paired t-test analysis. In the verification study, correlation between automated and manual methods was excellent (R2 = 0.85, p<0.05) with a negligible bias (0.003 mm) as determined by Bland Altman analysis. It is concluded that computerized analyzing method can automatically detect the instantaneous changes of the arterial walls in sequential B-mode images.

Previous studies have shown that exercise enhances cognitive and functional capacities in patients with Alzheimer's disease (AD). In this study, we investigated the effect of long-term (60 days) and short- term (10 days) exercise on the spatial memory deficits in an animal model of AD. Fifty male rats were divided into 5 groups; 1) intact, 2) sham, 3) sham-Alzheimer 4) Alzheimer-short term exercise and 5) Alzheimer-long term exercise. For spatial task evaluation, all groups were tested 5 days in a repeated-acquisition Morris water maze (MWM) tank task, and then tested in a probe trial, in which no escape platform was present, 1 week and 1 month later. Alzheimer’s disease was induced by bilateral lesioning of nucleus basalis magnocellularis (NBM) in rats and they were checked by MWM task. Alzheimer-short term exercise and Alzheimerlong term exercise groups were trained in treadmill and then were tested for 1 session in MWM tank task. Analysis of data showed that the time spent in the goal zone of the MWM tank during the 60 sec probe trial were significantly different in sham and Alzheimer groups (p<0.001). There was a significant difference in memory before and after short term exercise (p<0.001) and long term exercise (p<0.001) in Alzheimer groups. These data suggest that short-term and long-term treadmill running exercise improved spatial memory deficits in an animal model of AD. Keywords: Alzheimer's disease, spatial memory, exercise, Nucleus Basalis Magnocellularis.

Aging is the major risk factor for neurodegenerative diseases and oxidative stress is involved in the pathophysiology of these diseases. Oxidative stress can induce neuronal damages and modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. In this study, we investigated the possible antioxidant and neuroprotective properties of the polyphenolic antioxidant compound, Curcumin against homocysteine (Hcy) neurotoxicity. Curcumin (5, 15, 45 mg/kg) was injected intraperitonealy once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 μmol/μl) intracerebroventricular injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests were studied 24 h after the last curcumin or its vehicle injection. Also Histopathological studies and cell dencity in different regions of hippocampus was investigated. Hcy could induce lipid peroxidation and increase MDA and SOA levels in rat's brain. Additionally, Hcy impaired memory retention in passive avoidance learning test. However, Curcumin treatment decreased MDA and SOA levels significantly as well as improved learning and memory in rats. Histopathological analysis also indicated that Hcy could decrease hippocampus cell count and Curcumin inhibited this toxic effect. These results suggest that Hcy may induce lipid peroxidation in rat's brain and decrease hippocampus cells. Also polyphenol treatment (Curcumin) has the ability to improve learning and memory deficits by protecting the nervous system against Oxidative stress. Keywords: Homocysteine, Curcumin, Lipid peroxidation, Oxidative Stress