Physiology and Pharmacology
Volume:19 Issue: 1, Mar 2015

Considering the antiepileptogenic effects of repeated transcranial magnetic stimulation (rTMS), the effect of rTMS applied during amygdala kindling on spontaneous activity of hippocampal CA1 pyramidal neurons was investigated. A tripolar electrode was inserted in basolateral amygdala of Male Wistar rats. After a recovery period, animals received daily kindling stimulations until they reached stage 5 seizure. In one group of animals, rTMS at frequency of 1 Hz were applied to hippocampus once daily at 5 min after termination of kindling stimulations. 24 h after the last kindling stimulation, spontaneous activity of CA1 pyramidal neurons of the hippocampus was investigated using whole cell patch clamp technique. Kindling-induced seizures resulted in increment of spontaneous activity of hippocampal CA1 neurons, but application of rTMS during amygdala kindling prevented it. Moreover, rTMS administration inhibited the kindling-induced enhancement of afterdepolarization (ADP) amplitude and action potential duration. Results of this study suggest that rTMS exerts its anticonvulsant effect, in part, through preventing the amygdala kindling-induced increase in spontaneous activity and excitability of hippocampal CA1 pyramidal neurons.

Multiple sclerosis is a chronic inflammatory disease of central nervous system. The etiology of MS is slightly known, but genetic and environmental factors are reported. Vitamin D regulates gene expression and affects target cell functions. The aim of this study was to investigate the expression variation of IL-2 and IL-4 genes under vitamin D supplementation in patients with multiple sclerosis. In this study, blood samples were drawn from 32 patients before and after treatment with vitamin D. Quantitative real time PCR was used to measure IL-2 and IL-4 gene expression levels. Correlation analysis between the expression levels of genes and serum vitamin D, the Expanded Disability Status Scale (EDSS) as well as other clinical features of patients with MS was performed. No significant difference of IL-2 and IL-4 genes expression level was observed with vitamin D supplementation. We did not find significant correlation between IL-2 and IL-4 mRNA levels and EDSS score in multiple sclerosis patients. We did not find any difference between the expression of IL-2 and IL-4 genes before and after treatment with vitamin D that it may have some effects on the prevention of multiple sclerosis through other inflammatory factors and signaling pathways.

Noradrenergic cells in LC participate in the process of cortical activation and behavioral arousal. The evidence suggests that locus ceoruleus (LC) plays an important role in the sleep-wake cycle. The aim of this study was stereological estimation of cavity caused by lesion and assessment of sleep stages after bilateral lesion of the LC. Male Wistar rats weighting 250-275 gr were divided into four groups (control: n=6, sham: n=6, lesion1: n=6 and lesion2: n=6). 6 hydroxydopamine (6 OHDA) (2μg/0.5μl and 4μg/1μl) was sterotaxically injected bilaterally into LC to produced lesion. For sleep recording 3 EEG and 2 EMG electrodes were implanted respectively in the skull and dorsal neck muscle. Recordings were taken before and 7, 21 and 42 days after lesion. After 7 weeks, Rats first were anesthetized and then their brains were removed and cut in 7 μm serial sections and stained with cresyl violet. The volume of LC and the lesion induced cavity were evaluated through the stereological technique. Lesion - induced cavity volume (0.5 μl) was restricted to LC, whereas Another group (1 μl), total LC and structures adjacent to the LC were also damaged. A significant decrease was seen in non-rapid eye movement (NREM) and paradoxical sleep (PS) stages and a significant increase was seen in duration of wake and paradoxical sleep without atonia (PS-A) in lesion group in comparison with control and sham groups. The results of this study demonstrate 2μg/0.5μl 6-OHDA is suitable dose for LC lesion and bilateral lesion of LC causing disrupt wake, NREM, PS and also produce the PS-A.

During hemorrhagic shock (HS), the kidneys are one of the primary target organs involved. Oxidative stress is shown to be enhanced in different models of acute kidney injury (AKI). Remote ischemic preconditioning (RPC) by brief limb ischemia is considered to be a safe method to protect different organs from further damage. In this study, we investigated the effects of brief hind limb occlusion on protection against AKI and whether this protection is related to a reduction in oxidative stress. Twenty one rats were divided into three groups of seven rats. Sham-operated animals underwent surgical procedures, without hemorrhage. HS was induced by bleeding from a femoral arterial catheter to remove 44% of total blood volume. In RPC group, four cycles of lower limb ischemic preconditioning (5 min ischemia followed by 5 min reperfusion) were performed immediately before HS. Three hours later, plasma and renal tissue samples were collected for renal function monitoring and oxidative stress assessment. Compared with the sham group, HS resulted in renal dysfunction, significantly increased blood urea nitrogen (BUN), plasma creatinine (Cr) and renal malondialdehyde (MDA) levels as well as decreased superoxide dismutase (SOD) activity in the kidneys (P0.05). In the RPC group, renal function was significantly improved. Plasma Cr and BUN and renal MDA levels were significantly lower in RPC group comparing to HS group (P0.05). Renal SOD activity was significantly higher in RPC group compared to HS group (P0.05). These results demonstrate that induction of brief periods of lower limb ischemic preconditioning improves kidney function, restores SOD activity and reduces oxidative stress injury caused by hemorrhagic shock.

Regulators of G-protein signaling protein negatively control G protein -coupled receptor signaling duration by accelerating Gα subunit guanosine triphosphate hydrolysis. Since regulator of G-protein signaling4 has an important role in modulating morphine effects at the cellular level and the exact mechanism(s) of adrenalectomy-induced morphine sensitization have not been fully clarified, the present study was designed to determine the changes in the levels of RGS4 mRNA and protein in intact and adrenalectomized (ADX) morphine-treated rats. All experiments were carried out on male Wistar rats. The tail-flick test was used to assess the nociceptive threshold and corticosterone levels were measured by radioimmunoassay. The dorsal half of the lumbar spinal cord was assayed for the expression of RGS4 using semi-quantitative RT-PCR and immunoblotting. Results showed that the anti-nociceptive effect of intrathecal morphine (5 μg) was significantly increased in ADX rats. The levels of RGS4 mRNA and protein in ADX rats were similar to those in intact animals. However, morphine could elicit a significant increase in both mRNA and protein levels of RGS4 following adrenalectomy. In contrast, the pattern of RGS4 gene expression did not show significant changes in the lumbar spinal cord of intact animals after morphine injection. Our results demonstrate that in the absence of corticosterone, morphine increases RGS4 through promoting its gene expression.

Lead is one of the most important environmental pollutants due to its vast use in various industries. Lead accumulation in different organs, especially the brain, liver and kidneys can cause serious health problems. Lead exposure is more dangerous during fetal period and childhood. Timed pregnant female rats divided into 6 groups. Group 1served as control group and received tap water, group 2 received 500 mg/liter lead acetate in the drinking water from 5th day of gestation up to 25th day post-partum, group 3 received the same dose of lead acetate along with daily IP injection of 40mg/kg quercetin, Group 4 received the same dose of lead acetate along with 2g/liter vitamin C, groups 5 and 6 received vitamin C and quercetin respectively like groups 2 and 3 but without lead acetate. On the 25th day postpartum, 6 male pups in each group were deeply anesthetized by chloroform; livers were removed and processed for Hematoxyline- Eosin staining. The microscopic slides were photographed and liver tissue morphological characteristics were evaluated. Lead exposure caused extensive histopathologic changes in liver tissue including hepatocyte degradation, cell nucleus bifurcation and inflammation around hepatic veins. Quercetin and vitamin C treatment could prevent these pathologic changes to a considerable extent. Vitamin C in drinking water and quercetin via IP injection could protect the liver tissue against lead hepatotoxic effects.

The effects of cannabinoids (CBs) on synaptic plasticity of hippocampal dentate gyrus neurons have been shown in numerous studies. However, the effect of repeated exposure to cannabinoids on hippocampal function is not fully understood. In this study, using field potential recording, we investigated the effect of repeated administration of the nonselective CB receptor agonist WIN55212-2, and the CB1 receptor antagonist AM251, on both short- and long-term synaptic plasticity in dentate gyrus (DG) of hippocampus. Drugs were administered three times daily for seven consecutive days into lateral ventricle of rats. Short term synaptic plasticity was assessed by measuring paired-pulse index (PPI) in DG neurons after stimulation of perforant pathway. Long-term plasticity was assessed through measurement of both population spike (PS) amplitude and field excitatory postsynaptic potential (fEPSP) slope after high frequency stimulation (HFS) of DG neurons. Repeated administration of WIN55212-2 not only significantly decreased PPI in 20, 30 and 50 ms intervals but also blocked LTP. This effect was reversed by pretreatment of rats with CB1 receptor antagonist AM251. Moreover, AM251 by itself increased PPI in 10 and 20 ms interval stimulations, but had no effect on HFS-induced PS amplitude and fEPSP slope. These results suggest that repeated administration of cannabinoids could impair short term and long term synaptic plasticity that may be due to desensitization of cannabinoid receptors and/or changes in synaptic spine density of hippocampus which leads to alteration in short and long term memories that remains to be elucidated.

Cisplatin (CP) therapy may disturb cardiovascular system control. The objective of this study was to find baroreflex sensitivity (BRS) in CP-induced nephrotoxicity in rats. Eighteen male and female Wistar rats were randomly assigned to two groups; treated with CP (2.5 mg/kg/day) and the vehicle, for five consecutive days, and then were subjected to surgical procedure to determine BRS using three different doses (0.025, 0.05 and 0.1 mg/kg) of α-adrenergic receptor agonist phenylephrine (PE). Serum levels of blood urea nitrogen and creatinine, kidney weight, and kidney tissue damage score were increased in CP-treated animals. All doses of PE injection caused MAP increase and HR decrease. However, ΔMAP and ΔHR response to 0.1 mg/kg of PE were significantly lower in the CP-treated group (P<0.05). BRS also was increased in a dose-dependent manner by PE in vehicle-treated group, but this was not the case in the CP-treated animals, and significant difference in BRS was detected between the two groups (P<0.05) when 0.05 or 0.1 mg/kg of PE were infused. CP-induced nephrotoxicity attenuates BRS possibly due to peripheral effect on the vascular system.

The brain renin-angiotensin system (RAS) has been reported having a pathological role in age-related impairment in learning and memory. Therefore, angiotensin converting enzyme inhibitors (ACEi) are expected to have positive effects on memory. Longtime treatment with captopril (an angiotensin converting enzyme inhibitor) significantly attenuates the age-related impairment in learning and memory. In the present study, 24 month old male Wistar rats were divided into four experimental groups (n=8). Captopril treated groups received daily ip injections of captopril at doses of 5, 10, 15 mg/kg/day for one week, the forth group served as control and remained untreated. Learning process was assessed by the reference memory task in the Morris water maze. All rats received water maze training (4 trials/day for 5 days) to assess hippocampal dependent spatial learning and then received a 60-s probe test of spatial memory retention 24 h after the 20th trial. Over 5 days of training, captopril 5, 10, 15 mg/kg/day treatment significantly reduced the latency and path length to finding the escape platform. In probe trails (without platform), on the last day of training, the captopril -treated group spent significantly longer time in the platform quadrant than control animals. Among treated group, 10 /mg/Kg dosage of captopril induced the best rehearsals memory. These results confirm the previous studies that ACEi have a positive influence on memory and it was noticeable that even short time treatment by captopril can improve spatial memory in the aged rats.