Physiology and Pharmacology
Year:2008 | Volume:12 | Issue:3|Papers Count:15

Introduction: Sex hormones are one of the most important factors responsible for differences of learning and memory between males and females. High concentration of estrogen and androgen receptors and mechanism of testosterone and estrogen production in learning and memory center, especially in hippocampus show the role of these receptors, sex hormones and P450 enzymes in spatial memory. In this study we evaluated the effect of estradiol valerate (BV) and an aromatase inhibitor, anasterazole (An), on spatial learning and memory in Morris Water Maze. Methods: Adult male rats were bilaterally cannulated into the CAI region. After the recovery period, control groups received either DMSO 0.5 ml or DMSO 0.5 ml+ 0.5 ml. Different doses of EV (1, 2.5, 5, 10 and 15 mg/ 0.5 ml), An (0.25, 0.5 and mg/ 0.5 ml)and EV 15 mg/ 0.5 m1+ An 0.5 m/0.5ml were microinjected every day before training. EV and an were injected 30-35 min and 25-30 min before training, respectively. Results: Our results showed that escape latency and traveled distance were increased in EV 0.15 ml/ 0.5 ml group. We also observed that an decreased escape latency and traveled distance in a dose-dependent manner. Conclusion: EV impaired acquisition of spatial learning and memory but An improved it. However, when An and EV were administered together, An could not prevent EV-induced impairments.

Introduction: It has been reported that acute administration of morphine impairs learning and memory processes in rats. Furthermore, recent studies showed that Saffton extract improved ethanol-induced impairments of learning behaviors in mice, and also prevented ethanol-induced inhibition of hippocampal long-term potentiation. It can be postulated that there are some common mechanisms responsible for the morphine and ethanol-induced impairments of spatial learning and memory. Therefore in the present study we investigated the effects of Saffton extract on morphine induced learning and memory impairments in rat using Morris water maze (MWM).Methods: In the current study, male rats received Saffton extract (10, 30 or 50 mg/kg, i.p.) 30 minutes before injection of morphine (10 mg/kg, i.p.) or saline for 5 consecutive days. Animals of two control groups received only morphine or saline. Spatial learning and memory parameters in the same days in the (MWM) were tested and subjected to the ANOVA and followed by Tukey's test for multiple comparisons.Results: The data indicated that administration of morphine impaired formation of spatial learning and memory processes. Application of Saffton extract can improve adverse effects induced by morphine in a dose-dependent manner.Conclusion: It could be concluded that the extract of Saffron can inhibit morphine-induced impairments on spatial learning and memory in rats.

Introduction: The p19 line of embryonal carcinoma cells develop into neurons, astroglia and fibroblasts after aggregation and exposure to retinoic acid (RA). Dehydroepiandrosterone (DHEA) is a neurosteroid, which can increase the proliferation of human neural stem cells (NSC) and positively regulate the number of neurons produced. This study was initiated to assess the effect of DHEA on neural progenitor cells derived from p19 embryonal carcinoma stem cells. Methods: p19 cells were suspended in DMEM containing 5% FBS in bacterial-grade Petri dishes in the presence of RA and DHEA at different concentrations for 6 days. Serum concentration was decreased to 3% on days 5 and 6. The aggregates were then collected and processed for flow cytometry, immunocytochemistry and RT-PCR analyses. Cells were trypsinized for dispersion and were placed in to poly-L-lysine (10 mg/ml) coated tissue culture dishes without RA and DHEA for 4 days. Differentiated cells were then evaluated by phase contrast microscopy.Results: Flow cytometry analyses of Nestin and Brdu/Nestin showed percent Nestin positive and proliferating Nestin positive cells in different groups including DHEA and RA groups. Brdul/Nestin immunochemistry confirmed proliferation of Nestin positive cells and also RT-PCR analysis showed the expression of proneural markers and estrogen receptor genes. Result showed that RA + DHEA (mM) significantly increased the number of Nestin positive and newly formed Nestin positive cells compared to other groups.Conclusion: These results showed that DHEA accompanied by RA significantly increased the number of Nestin positive and newly formed Nestin positive cells derived from p19 embryonal carcinoma cells but in comparison to RA could not induce neural progenitor cells.

Introduction: Orexin-A and B (Hypocretin I and 2) are neuropeptides that are mostly expressed in the posterior and lateral hypothalamus (LH). Intracisternal (ICV) and intratechal (IT) injections of orexin-A (hypocretin-l) have been shown to elicit analgesic responses in formalin test. However, the locations of central sites that may mediate these effects have not been clearly elucidated. Orexin-containing fibers are projected to periaqueductal gray matter (PAG), which is involved in pain modulation.Methods: Behavioral study was done on male Sprague Dawley rats (200-300 g) in formalin induced nociceptive behaviour.Results: Intra-PAG microinjection of orexin-Aproduced a dose-dependent inhibition of formalin-evoked behavior in interphase and phase 2, but not in phase 1, indicating an antinociceptive role of exogenous orexin-A in the PAG. Analgesic effect of orexin-A was less than and specific to inter- and late phase of formalin test, when compared with that of morphine (5 mg/0.5ml) after intra-PAG administration.Conclusion: The obtained results suggest that orexin-A plays an anti-nociceptiverole in PAG, on the interphase and late phase of formalin test in rats. So it is possible that orexin-A might be involved in the mechanisms of inter- and last phases of formalin induced behaviours.

Introduction: Huntington's disease is an inherited neurodegenerative disease associated with widespread neuronal degeneration in neostriatum and neocortex. Progress of the disease causes disabling clinical effects on movements, cognition and physiology of the body, and finally results in death. Currently, there is no effective therapeutic strategy for diminishing the motor disabilities of Huntington's disease. In recent years, cellular transplantation has been an effective therapeutic method for neurodegenerative diseases.Methods: In this study, the effects of bone marrow derived mesenchymal stem cells were assessed in an animal model of Huntington's disease. After causing ipsilateral lesion in the striatum with quinolinic acid, bone marrow derived mesenchymal stem cells which had been isolated and purified from 4-6 weeks old rats, were transplanted into the damaged striatum. The efficiency of cellular transplantation for improvement of motor disabilities was assessed by cylinder test and apomorphin induced rotation tests, during eight weeks after the transplant. Results: Results showed significant improvement (p < 0.0001) in motor disability and the percentage of striatal atrophy.Conclusion: According to these results, cell therapy with bone marrow derived adult stem cells seems promising for treatment of neurodegenerative diseases, especially Huntington's disease.

Introduction: Repeated hyperglycemia play an important role in development of atherosclerosis in diabetic patients. Endothelium is the first-line defense against atherosclerosis and nitric oxide has a major role in this task. In this study, changes in plasma concentration of nitric oxide metabolites (NOx) during glucose tolerance test were evaluated in type II diabetic rats.Methods: Male neonatal Wistar rats were divided into control and diabetic groups. Type II diabetes was induced by administration of Streptozotocin (100 mg/kg, i.p.) to neonatal rats on day 2. Plasma glucose and NOx concentration were measured on days 7, 30, 45, 60, and 75. Intravenous glucose tolerance test was done in adult rats and blood samples were collected 0, 5, 10, 30, and 60 min after glucose infusion for determining plasma glucose, insulin, and NOx. Two-way mixed (between-within) ANOVA was used for comparing data.Results: Plasma glucose was returned to basal values 60 min after glucose injection in the control group, while in diabetic rats it was higher than basal levels (P < 0.001). After glucose injection, plasma insulin concentration was increased to 4.5 and 1.9 folds in control and diabetic groups, respectively. Basal NOx concentration was higher in diabetic rats (50.4 %6.4 vs. 28.8 %3.8 ¥mol/l, P < 0.05). During glucose tolerance test there was 35 and 62 % fall in plasma NOx concentration in control and diabetic groups, respectively. This reduction returned to basal values after 30 min in the control group, while in diabetic rats it was 17% less than basal levels 60 min after glucose injection. Conclusion: Decreased nitric oxide production or increased degradation may be the cause of endothelial dysfunction and atherosclerosis in type II diabetes.

Introduction: Today the design and structural characterization of mini-proteins with a compact folded structure provide insight into the complex architecture of proteins and has long been a challenging issue in structural-functional studies. Alpha neurotoxins from snake venom have a distinct folded structure comprised of a disulphide core and three loops or "fingers"; each of these loops are considered as a separate functional domain. Because of the selectivity and specificity of snake alpha neurotoxins, they are ideal candidates for structural-functional studies. Methods: With the assumption that each "loop" in the structure of alpha neurotoxin is able to fold as a structurally independent unit and could possibly have functional properties, we have minimized the structure of a long-chain alpha neurotoxin into 18 and 31 amino acid peptides using solid-phase synthesis and cloning methods, respectively. The molecules are structurally studied using circular dichroism spectroscopy and also in vitro using organ bath apparatus and chick biventer cervicis muscle (CBCM).Results: The 18 and 31-mer peptides form predominant beta structures (b-turnand b-sheet/alphahelix) in aqueous solutions which vary with solvent ionic strength. Data from in vitro and in sitico studies indicate that these minimized structures block the twitches in CBCM with concentrations higher than 0.5 11M; and this effect is absolutely dose dependent. On the other hand, the long-chain alpha neurotoxin completely and irreversibly blocks the CBCM even at 50 nanomolar concentration and both effects are post synaptic.Conclusion: These data support the primary assumption that the peptides derived from the second loop of snake alpha neurotoxin can have a distinct folded structure and also exist as an independent biological unit.

Introduction: Beta-2 adrenoceptors are important in blood flow regulation. Responsiveness of these receptors is decreased in diabetic angiopathy, in contrast to inflammation, where this responsiveness is increased. Considering these opposite effects, the aim of this study was to investigate the vasodilatory response of knee joint blood vessels to salbutamol (a Beta-2 adrenoceptor agonist) in inflamedjoints of diabetic rats.Methods: Acute knee joint inflammation was induced by intraarticular injection of kaolin 4% and induction of diabetes was performed by streptozotocin (55 mg/kg). Wistar rats weighting 200-300 g were used. The animals were divided in 5 groups; control, saline, diabetic, inflammatory and diabetic-inflammatory. Blood flow of knee joint was measured using laser Doppler flowmeter technique (LDF). Vasodilatation of articular micro vasculature was measured in response to topical application of different concentration of salbutamol (10 -11-10 -1 M). Results: Data obtained in this study showed that: 1- Acute inflammation caused significantly less increments in knee joint diameter and perimeter in diabetic compared to non-diabetic rats. 2- Responsiveness ofBeta-2 adrenoceptors was increased in kaolin-induced acute inflammation in non-diabetic rats. 3- In diabetic rats, kaolin-induced acute inflammation could not increase the responsiveness ofBeta-2 adrenoceptors.Conclusion: We conclude that diabetes inhibits the increasing effects of acute inflammation on responsiveness of Beta-2 adrenoceptors.

Introduction: Ascorbic acid (AA) acts as an antioxidant in the central nervous system (CNS) of the mammalians. It is released from some nerve endings together with neurotransmitters and previous studies have shown that ascorbic acid could affect learning as well as memory. In this study, the effect of intracerebro ventricular (ICV) injection of ascorbic acid on spatial learning and memory was examined by Morris water maze.Methods: 42 adult male NMRI rats weighing 250-300 g were used in this study. Cannulas were implanted bilaterally in the lateral ventricles (LV) (AP=0.8, LA=±1.5, DV=3.4). After the recovery period, the animals were divided into 6 groups. The control group received no injection. Four groups were assigned as experimental groups and received different doses of ascorbic acid (25, 50, 100 and 150 mg/kg) and the 6th group was assigned as the shamoperated group that received normal saline as vehicle. Injections were given in 5 consecutive days. Thirty min after each injection the rats were trained in the Morris Water Maze (MWM) and spatial learning and memory parameters were recorded and then analyzed.Results: ICV injection of ascorbic acid reduced spatial learning and memory in rats. This reduction reached statistical significance with the dose of 100 mg/kg of ascorbic acid.Conclusion: It can be concluded that ascorbic acid decreases spatial learning and memory, which can be due to direct or indirect interference with the effects of neurotransmitters.

Introduction: Doxorubicin is frequently used for treatment of several types of cancer, but cardiac toxicity has limited the use of this drug. Corticosteroids may prevent doxorubicin induced cardiotoxicity. Therefore the aim of this study was to evaluate mouse embryonic stem cells derived cardiomyocytes as a model to assess the effects of doxorubicin and dexamethasone.Methods: Mouse embryonic stem cells derived cardiomyocytes were treated with different concentrations of doxorubicin for 24 hours and the results were compared with control group. In order to examine the effect of dexamethasone on cardiotoxicity, mouse embryonic stem cells derived cardiomyocytes were either exposed to 0.1, 1 or 10 mM dexamethasone 24 hours prior to exposure to doxorubicin or exposed to dexamethasone 24 hours before and during exposure to doxorubicin. Each group was compared with cells that were treated with only doxorubicin or dexamethasone.Results: 5 mM doxorubicin was selected as the lowest dose that ceased heart beats in more than 50% of mouse embryonic stem cells derived cardiomyocytes. Results revealed that 10 mM dexamethasone for 24 hours before treatment with doxorubicin has protective effect on doxorubicin induced cardiotoxicity.Conclusion: The overall results obtained in this model are in accordance with previous literature. Thus suggesting that mouse embryonic stem cells derived cardiomyocytes is a suitable model for assessment of cardiotoxic effects of drugs.

Introduction: Zinc is an essential trace element that plays an important role in the synaptic plasticity and modulation of the CNS activity and is also involved in learning and memory. Synaptic vesicle zinc in the hippocampus area exerts modulatory effects on NMDA glutamate receptors.Methods: In this study, the effects of intra hippocampal administration of NMDA agonist and antagonist in the presence and absence of ZnCl2 was investigated on passive avoidance learning and memory by using step down task in adult male rats. Animals were divided into 10 groups (n = 8 each group). Control group, second group received NMDA 0.1 mg/rat in 1 ml saline for 4 days. Sham group received saline with the same volume. Fourth group received MK-801 1 mg/rat in 1 ml saline 10 min before training for 4 days. Sham group received saline in the same volume. Groups 6-10 received 30 mg/kg/day Zncl2 in drinking water for 2 weeks. Sixth group received only Zncl2, but groups 7, 8, 9, and 10 received drug and saline in the same conditions as groups 2, 3, 4 and 5 in addition to Zncl2 in their drinking water.Results: Our experiments showed that consumption of 30 mg/kg/day Zncl2 impaired learning and memory in adult male rats (P < 0.05). Administration of NMDA improved the impairments caused by Zncl2 consumption (P < 0.05), while the administration of MK-801 increased the impairments.Conclusion: It seems that zinc impairs passive avoidance learning and memory by modulating the subunits of NMDA receptors in hippocampus.