The Role of 5-HT1A Receptors and Neuronal Nitric Oxide Synthase in a Seizur Induced Kindling Model in Rats.

BACKGROUND AND OBJECTIVE: Dentate gyrus (DG) has a high density of 5-HT1A receptors. It has neural nitric oxide synthase (nNOS), which is involved in neural excitability. The purpose of this study was to investigate the role of 5-HT1A receptors and nNOS of DG in perforant path kindling model of epilepsy. MATERIAL AND METHODS: To achieve this purpose, a receptor antagonist (WAY100635, 0.1 mg/kg, intracerebroventricular, i.c.v) and neuronal nitric oxide synthase inhibitor (7-NI, 15 mg/kg, intraperitoneal, i.p.) were injected during kindling aquisition. Adult male Wistar rats (280 ± 20 g) were used in this study Animals were kindled through the daily administration of brief electrical stimulations (10 stimulations per day) to the perforant pathway. Field potential recordings were performed for 20 min in DG beforehand. Additionally, glial fibrillary acidic protein (GFAP) expression rate in the DG was determined using immunohistochemistry as a highly specific marker for glia. RESULTS: WAY100635 (0.1 mg/kg) significantly attenuated the kindling threshold compared to the kindled + vehicle group (P < 0.001). The co-administration of WAY100635 with 7-NI, exerted a significant anticonvulsive effect. Furthermore, the slope of field Excitatory Post Synaptic Potentials (fEPSP) at the end of 10 days in the kindled + 7-NI + WAY100635 group was significantly lower than in the kindled + vehicle group (P < 0.001). Furthermore, immunohistochemistry showed that the density of GAFP+ cells in the kindled + 7-NI + WAY100635 group was significantly higher than in the kindled + vehicle group (P < 0.001). CONCLUSION: Our data demonstrate that antagonists of 5-HT1A receptors have proconvulsive effects and that astrocyte cells are involved in this process, while nNOS has an inhibitory effect on neuronal excitability.

Effect of conjugated linoleic acid supplementation on quality of life in rectal cancer patients undergoing preoperative Chemoradiotherapy.

OBJECTIVES: This study set out with the aim of evaluating the effect of conjugated linoleic acid (CLA) supplementation on quality of life in rectal cancer patients undergoing to preoperative chemoradiotherapy. METHODS: In this study, 33 volunteer patients with rectal cancer treated with preoperative chemoradiotherapy were allocated in the CLA (n=16) and the placebo groups (n=17). The CLA group and placebo groups received 3 gr CLA/d and 4 placebo capsules for 6 weeks respectively. Before and after intervention, quality of life of patients was assessed by EORTC QLQ-C30. RESULTS: At the end of study, the mean scores of physical function, role function, and cognitive function enhanced significantly in the CLA group while reduced remarkably in the placebo group. Symptom scales improved in the CLA group at the end of study. Comparison of changes in fatigue, pain and diarrhea scores were statistically significant between two study groups (P<0.05). When we compared the global health status scores between two groups, significant changes were observed (P<0.001). CONCLUSION: It appears that CLA may be helpful in rectal cancer patients by improving global quality of life. Although, other clinical trials with large sample size are needed to achieve more precise results.

Inhibition of microglial activity alters spinal wide dynamic range neuron discharge and reduces microglial Toll-like receptor 4 expression in neuropathic rats.

It is believed that neuropathic pain results from aberrant neuronal discharges although some evidence suggests that the activation of glia cells contributes to pain after an injury to the nervous system. This study aimed to evaluate the role of microglial activation on the hyper-responsiveness of wide dynamic range neurons (WDR) and Toll-like receptor 4 (TLR4) expressions in a chronic constriction injury (CCI) model of neuropathic pain in rats. Adult male Wistar rats (230 ± 30 g) underwent surgery for induction of CCI neuropathy. Six days after surgery, administration of minocycline (10, 20, and 40 mg/kg, i.p.) was initiated and continued until day 14. After administration of the last dose of minocycline or saline, a behavioral test was conducted, then animals were sacrificed and lumbar segments of the spinal cord were collected for Western blot analysis of TLR4 expression. The electrophysiological properties of WDR neurons were investigated by single unit recordings in separate groups. The findings showed that after CCI, in parallel with thermal hyperalgesia, the expression of TLR4 in the spinal cord and the evoked response of the WDR neurons to electrical, mechanical, and thermal stimulation significantly increased. Post-injury administration of minocycline effectively decreased thermal hyperalgesia, TLR4 expression, and hyper-responsiveness of WDR neurons in CCI rats. The results of this study indicate that post-injury, repeated administration of minocycline attenuated neuropathic pain by suppressing microglia activation and reducing WDR neuron hyper-responsiveness. This study confirms that post-injury modulation of microglial activity is a new strategy for treating neuropathic pain.

The role of ethanol on the anticonvulsant effect of valproic acid and cortical microvascular changes after epileptogenesis in mice.

There have been conflicting reports regarding the role of ethanol in seizure. Another effect of ethanol is vascular damage in cerebral tissue. This study investigates the influence of ethanol on antiepileptic efficacy of valproic acid (VPA) and cerebral microvascular structure. In this study, four groups of mice (25-30 g) received pentylenetetrazole (PTZ) i.p. (37 mg/kg) every other day. Different groups of animals received an injection of saline, ethanol (1 g/kg), VPA (100 mg/kg), or VPA and ethanol 30 min before PTZ. Animals in groups 5 and 6 received only ethanol and saline, respectively. After recording seizure parameters, the animals were sacrificed under deep anesthesia and the brains of the animals were removed and fixed, thereafter coronal sections were prepared from cerebral cortex. Then, the cerebral microvessels were counted in microscopic sections after hematoxylin-eosin staining. Ethanol injection (1 g/kg) for 7 days decreased stage 4 duration and increased latency to the onset of stage 1 and stage 4 of seizure (p < 0.001). Concomitant injection of VPA (5 min before ethanol) and ethanol had significantly stronger anticonvulsant effects than VPA alone (p < 0.001). Furthermore, the findings showed that not only the cerebral microvessels increased significantly in ethanol group compared with saline group (p < 0.05), but also there were morphological changes in vascular endothelium in ethanol group. The obtained results show that short-term ethanol administration has anticonvulsant effects along with VPA, and enhances the anticonvulsant effects of VPA. Furthermore, it is possible that VPA leads to decreased ethanol-induced vascular damage.

Validation of nutritional risk index method against patient-generated subjective global assessment in screening malnutrition in colorectal cancer patients.

OBJECTIVE: To validate malnutrition screening tool of nutrition risk index (NRI) against patient-generated subjective global assessment (PG-SGA) as a gold standard tool in colorectal cancer patients before radiotherapy. METHODS: Nutritional status of 52 volunteer colorectal cancer patients with a mean age of 54.1±16.8 years who referred to radiotherapy center were assessed by PG-SGA (gold standard method) and NRI. Serum albumin levels of patients were determined by colorimetric method. A contingency table was used to determine the sensitivity, specificity, and predictive value of the NRI in screening patients at risk of malnutrition, in comparison with the PG-SGA in patients before radiotherapy. RESULTS: The findings of PG-SGA and NRI showed that 52% and 45% of patients in our study were moderately or severely malnourished respectively. The NRI had a sensitivity of 66% and a specificity of 60% against PG-SGA. The positive predictive value was 64% and the negative predicative value was 62%. The agreement between NRI and PG-SGA was statistically insignificant (kappa =0.267; P>0.05). CONCLUSIONS: The findings of present study showed that the prevalence of malnutrition was high in patients with colorectal cancer. Moreover, NRI method had low sensitivity and specificity in assessing nutritional status of patients with cancer. It seems that the combination of anthropometric, laboratory parameters and a subjective scoring system may be helpful tools in screening of malnutrition in cancer patients.

Determination of toxic metal burden and related risk factors in pregnant women: a biological monitoring in Sabzevar, Iran.

Nowadays, the adverse effect of toxic metals on humans is well known, especially in the fetal period such as preventing cognitive development and congenital abnormalities of the central nervous system. Hence, this study aims to evaluate the toxic metal burden in mothers and newborns in Sabzevar. Obtained data can be useful for authorities in public health issues. To determine heavy metals in placental blood and umbilical cord blood, one hundred eighty blood samples were taken from ninety mothers referred to Shahidan Mobini Hospital for delivery. The amount of metals in samples was analyzed using inductively coupled plasma optical emission spectrometry (ICP OES). The results of this study revealed that 21.52%, 26.19%, and 60.71% of maternal blood samples (placental blood) and 16.47%, 56.47%, and 20% of umbilical cord blood samples were higher than the US center for disease control (CDC) recommended levels for Pb, Cd, and As respectively. According to the multiple linear regression analysis, the Pb (p = 0.054), As (p < 0.001), and Se (p < 0.001) levels had an association with the mother's living area. Also, there was a significant association between Se (0.021) and the age of the mother. However, the Se values in its optimum concentrations in the blood (60-140 µg/L) can decrease the adverse effects of toxic metals, 72.5% of the pregnant women had Se values below the 60 µg/L and only 6% of pregnant women had Se levels higher than 140 µg/L. We concluded that the mothers inhabiting the rural areas need more Se sources in their diets.

The Effect of 6-gingerol on Growth Factors and Apoptosis Indices in Rats Exposed to Gold Nanoparticles.

INTRODUCTION: Research has shown that gold nanoparticles (AuNPs) can damage the physiological processes of brain tissue. Given the antioxidant properties of Gingerol (GING), this study aimed to determine the protective effect of 6-gingerol on hippocampal levels of Brain-Derived Neurotrophic Factor (BDNF), Nerve Growth Factor (NGF), DNA oxidative damage, and the amount of Bax and Bcl2 apoptosis indices of rats exposed to AuNPs. METHODS: A total of 42 male Wistar rats were divided into four groups: control (30 days 0.5 mL saline), AuNPs (one time injection of 0.5 mL AuNPs, 200 ppm and 60 Nm + 30 days 0.5 mL saline), AuNPs+GING 50 (one time injection of 0.5 mL AuNPs, 200 ppm and 60 Nm + 30 days 0.5 mL density of gingerol 50 mg/kg), and AuNPs+GING100 (one time injection of 0.5 mL AuNPs, 200 ppm and 60 Nm + 30 days 0.5 mL density of gingerol 100 mg/kg). At the end of the treatment period, the hippocampal levels of NGF, BDNF, 8-hydroxy-desoxyguanosine (8-HOdG), and apoptotic indices of Bax and Bcl-2 were assessed with the ELISA method. RESULTS: Compared with the AuNPs group, hippocampal levels of BDNF, NGF, and Bcl-2 in rats in the AuNPs+GING 50 and AuNPs+GING 100 groups significantly increased dose-dependently. However, the hippocampal levels of Bax and 8-HOdG significantly decreased dose-dependently (P<0.05). CONCLUSION: According to obtained results, gingerol may improve hippocampal BDNF and NGF levels in rats exposed to AuNPs, probably by reducing apoptosis and oxidative DNA damage.

The relationship between dietary intakes and prevalence of irritable bowel syndrome in adolescent girls: A cross-sectional study.

BACKGROUND: Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder (FGID) leading to substantial reduction in quality of life. This study was undertaken to assess the relationship between diet and prevalence of IBS in female adolescents. METHODS: In this cross-sectional study, data were examined on 988 adolescent girls from different areas of Mashhad and Sabzevar cities, Iran. A 168-item validated and reliable food frequency questionnaire (FFQ) for dietary intake was used in all the study participants. A diagnosis of IBS was made using the Rome III criteria. RESULTS: Dietary macronutrients, energy, and selected micronutrients of IBS patients were similar to healthy subjects. Comparing the intake of caffeine between groups with and without IBS showed a higher level of consumption in the individuals with IBS (p-value = 0.02; p trend = 0.03). There was a significant positive association between caffeine intake and risk of IBS (odds ratio [OR] = 1.88, after adjustment for potential confounding variables). Although there was no significant difference in intakes of total dietary fiber (p-value = 0.23) and insoluble dietary fiber (p-value = 0.09) between IBS-positive and IBS-negative subjects, their soluble dietary fiber intake was significantly different (p-value = 0.02, a significant negative association was seen between soluble dietary fiber intake and IBS prevalence, after adjustment for potential confounding variables [p trend = 0.02; OR = 0.59]). CONCLUSIONS: The higher intake of caffeine was positively associated with IBS prevalence. Additionally, a negative association was seen between soluble dietary fiber intake and the chance of having IBS.

Efficacy and tolerability of hydroalcoholic extract of Paeonia officinalis in children with intractable epilepsy: An open-label pilot study.

Despite a wide range of medications available to control epilepsy, seizures in more than 30 % of patients remain uncontrolled. However, in traditional medicine, Paeonia officinalis (P. officinalis), a native perennial herb of Southern Europe and Western Asia, has been used for an anticonvulsant effect for over 2000 years globally. In an open-label pilot study implemented on 30 children with intractable epilepsy aged 1-14 years, the hydroalcoholic extract of P. officinalis was administered. This study's purpose was to assess the efficacy and tolerability of the P. officinalis extract as an adjunct therapy to a patient's antiseizure medications in reducing the frequency and duration of the seizures in childhood intractable epilepsy. The mean frequency of seizures decreased significantly during treatment with the P. officinalis extract (P < 0.05). At the end of the intervention, 62.5 % and 36.7 % of the patients showed a≥50 % and a≥75 % reduction in seizure frequency, respectively. Regarding safety and tolerability, no serious adverse events occurred during the trial, although restlessness was reported in one child and the other children who experienced constipation, stopped treatment. The results show that the P. officinalis root extract was well tolerated and has contributed to a significant improvement in seizure control in children with medically intractable epilepsy. This trial was registered with the Iranian Registry of Clinical Trials (www.irct.ir; registration number: IRCT20131125015533N2.

The antiepileptogenic effect of electrical stimulation at different low frequencies is accompanied with change in adenosine receptors gene expression in rats.

PURPOSE: Previous studies have shown that the anticonvulsant effects of low-frequency stimulation (LFS) can be affected by activation of adenosine receptors. In the present study, the effect of LFS at different frequencies on kindling rate and adenosine receptors gene expression was investigated. METHODS: Animals were kindled by perforant path stimulation in a rapid kindling manner. LFS (0.5, 1, and 5 Hz) was applied after termination of each kindling stimulation. Seizure severity was measured according to behavioral and electrophysiologic parameters. At the end of the experiments, adenosine A(1) and A(2A) receptor gene expression were measured. RESULTS: The inhibitory effect of LFS on kindling acquisition was observed at all frequencies. In addition, the inhibitory action of LFS on enhancement of field excitatory postsynaptic potential slope and population spike amplitude during kindling acquisition was not affected by the LFS frequency. However, the effects of LFS on paired-pulse recordings were greater at frequency of 5 Hz. Application of LFS during kindling acquisition also prevented the kindling induced decrease in the A(1) receptor gene expression and attenuated the level of A(2A) receptor gene expression in the dentate gyrus. These effects were also greater at the frequency of 5 Hz. DISCUSSION: According to these data, it may be suggested that the antiepileptogenic effects of LFS, developed through inhibition of synaptic transmission in the dentate gyrus, is mediated somehow through preventing the decrease of A(1) receptor and through attenuating the A(2A) receptor gene expression. These effects might be dependent on the frequency of LFS.

The effect of harmaline on seizures induced by amygdala kindling in rats.

OBJECTIVE: Harmaline and other beta-carbolines act as an inverse agonist for GABA-A receptors and cause central nervous system stimulation and anxiety; thus, it may act hypothetically as a potential seizure augmenter. To examine the hypothesis, the effect of harmaline during the seizures induced by amygdala kindling is investigated here. METHODS: Seven groups of male rats were kindled by daily electrical stimulation of the amygdala. After being kindled, Groups I-III, respectively, received 5, 15 and 50 mg/kg harmaline through intraperitoneal injection. The rats in Groups IV and V received vehicle daily (1 ml/kg) and harmaline (5 mg/kg) daily through intraperitoneal injection. Groups VI and VII received artificial cerebrospinal fluid and harmaline (50 mM) through intraventricular injection, respectively. RESULTS: In addition to significant increase of some seizure parameters in the fully kindled groups, harmaline significantly increased cumulative afterdischarge duration (P < 0.05) and decreased stage 1 latency (P < 0.01) in the acquisition groups (Groups V and VII). In Group VII, seizure duration showed a significant increase (P < 0.01) while stage 1 latency and stage 4 latency decreased significantly (P < 0.01). DISCUSSION: According to the results, it is suggested that harmaline may increase neuronal activity and the production of high-frequency action potentials by stimulating NMDA receptors and inhibiting GABA receptors. Overall, drugs and plants containing harmaline may be harmful to epileptic-susceptible people during some traditionally and costume treatments, so these should be avoided.

New anthropometric indices in the definition of metabolic syndrome in pediatrics.

Pediatrics metabolic syndrome (MetS) may be associated with the risk of development of chronic diseases in adulthood; however, the definition of pediatric MetS is unclear, and may vary with ethnicity. The primary goal of this study was to determine the best anthropometric predictors for pediatric MetS. For this purpose, 988 high school girls were recruited. Anthropometric indices and biochemical parameters were measured using standard procedures. The adapted MetS for pediatrics, including the IDF, NCEP, and two modified-NCEPs (Cook's and DeFerranti's) were used to establish a diagnosis of MetS. Statistical analysis was performed using SPSS and MedCalc softwares. Except for body frame size (r), the values for anthropometric indices were significantly lower in an individual without MetS. Waist to height (WHtR), BMI and hip circumference (HiC) showed the strongest association with the different MetS definitions. For the IDF definition, the highest sensitivity and specificity were observed for HiC (100.0, 85.2) and WHtR (100.0, 84.7); while for the NCEP definition, the r index showed the highest sensitivity (85.0); but low specificity made it inapplicable. For the Cook's definition of MetS, wrist circumference (WrC), HiC, WHtR, BMI and SR had similar sensitivity values with WC (92.9%), and HiC (85.3%) have the highest specificity. WHtR (86.05, 80.5), SR (86.05, 82.7) and HiC (76.7, 87.0) sensitivity and specificity were the best indexes for DeFerranti's criteria. Based on this date, we concluded that HiC and WHtR might be helpful as auxiliary indexes for pediatric MetS definition; however, further studies are required in both genders.

The role of serotonin and its receptors on the anticonvulsant effect of curcumin in pentylenetetrazol-induced seizures.

AIM: Curcumin, derived from turmeric, has been demonstrated to be effective in controlling seizures, although the exact mechanism is yet unknown. In this study, the role of serotonin and its receptors in the anticonvulsant effect of curcumin was evaluated in mice. MAIN METHODS: Total 110 mice were randomly divided into 11 groups (n = 10). In the first to the fourth groups, the role of curcumin (150 mg/kg, i.p) and serotonin (PCPA (100 mg/kg); was used to deplete the brain serotonin levels) was investigated. The fifth group first received NAD-299 (4 mg/kg, sc), RS-102221 (5 mg/kg, i.p), SDZ205-557 Hydrochloride (1 mg/kg, i.p), and SB 26997 (10 mg/kg, i.p), then curcumin. The sixth group received NAD-299, curcumin. The animals in the seventh to ninth groups received 5-HT2C, 5-HT4, and 5-HT7 antagonists, respectively, with curcumin. The tenth group received HTR2C antagonist and the eleventh group received HTR4 antagonist. In all animals 25 min after curcumin PTZ (80 mg/kg; i.p) was injected. KEY FINDINGS: PCPA not only inhibited the anticonvulsant action of curcumin, but also reversed some of its anticonvulsant effect. The 5-HT1A, 5-HT2C and 5-HT4 antagonists diminished but 5-HT7 antagonist strengthened the anticonvulsant effect of curcumin. Evaluation of gene expression using real-time PCR confirmed that only 5-HT7 gene expression was reduced after curcumin injection. SIGNIFICANCE: According to these results, it may be suggested that curcumin exerts anticonvulsive effects by increasing the serotonin levels in the brain that influence receptors, including 5-HT1A, 5-HT2C, and 5-HT4 and likely through the reduction of 5-HT7 gene expression.

Effect of different patterns of low-frequency stimulation on piriform cortex kindled seizures.

Low-frequency stimulation (LFS) is an antiepileptic and antiepileptogenic electrical stimulation. In this study the effect of changes in some LFS (1Hz, monophasic square wave) parameters (intensity, pulse duration and train duration) on piriform cortex kindled seizures was investigated both in fully kindled rats and during kindling acquisition. In fully kindled animals, application of different patterns of LFS immediately before kindling stimulation had no significant effect on seizure parameters. However, daily (15 min) application of LFS (0.1 ms pulse duration at intensity equal to after-discharge threshold (ADT) and 1 ms pulse duration at intensity equal to 1/4 ADT) during inter-seizure interval of 7 days significantly reduced the stage 5 duration of the next kindled seizure. Application of the same two LFS protocols for 3 days and 2 weeks had no effect on seizure parameters. The effect of LFS was also tested using different paradigms during kindling acquisition. When LFS (0.1 and 1 ms pulse duration, intensity equal to ADT and 1/4 ADT) was delivered daily after each kindling stimulation, it could significantly decrease after-discharge duration in various days during kindling development. In this experiment, only LFS with 0.1 ms pulse duration and intensity equal to ADT significantly delayed the appearance of seizure stages 1 and 2. According to obtained results, it may be concluded that in fully kindled rats application of different patterns of LFS before kindling stimulation has no anticonvulsant effect, but it can exert an inhibitory effect when applied during an inter-seizure interval of 7 days. In addition, LFS has antiepileptogenic effect during kindling acquisition. These effects depend on the applied LFS parameters (e.g. intensity, pulse duration and train duration).

Effect of low frequency stimulation of perforant path on kindling rate and synaptic transmission in the dentate gyrus during kindling acquisition in rats.

Low frequency stimulation (LFS) has an inhibitory effect on kindling acquisition. In the present study the effect of the perforant path LFS on induction of rapid perforant path kindled seizures and synaptic transmission in the dentate gyrus was investigated. Animals were kindled by perforant path stimulation in a rapid kindling manner (12 stimulations per day). In one group of animals LFS (0.1 ms pulse duration at 1 Hz, 200 pulses, and 50-150 microA) was applied to perforant path, immediately after termination of each rapid kindling stimulation. Application of LFS significantly retarded the kindling acquisition and increased the number of stimulations to achieved different kindled seizure stages. LFS also prevented an increment in the slope of field excitatory postsynaptic potentials and population spike amplitude during kindling. In addition, LFS significantly reduced the marked increase in early (10-50 ms intervals) and late (300-1000 ms intervals) paired-pulse depression induced by kindling. According to obtained results, it may be suggested that LFS of perforant path has a significant antiepileptogenic effect through inhibition of synaptic transmission in dentate gyrus. Meanwhile, LFS prevents an increase in the paired-pulse depression during kindling acquisition.

Do sufficient vitamin D levels at the end of summer in children and adolescents provide an assurance of vitamin D sufficiency at the end of winter? A cohort study.

BACKGROUND: The changes in serum 25-hydroxyvitamin D (25(OH)D) in adolescents from summer to winter and optimal serum vitamin D levels in the summer to ensure adequate vitamin D levels at the end of winter are currently unknown. This study was conducted to address this knowledge gap. METHODS: The study was conducted as a cohort study. Sixty-eight participants aged 7-18 years and who had sufficient vitamin D levels at the end of the summer in 2011 were selected using stratified random sampling. Subsequently, the participants' vitamin D levels were measured at the end of the winter in 2012. A receiver operating characteristic (ROC) curve was used to determine optimal cutoff points for vitamin D at the end of the summer to predict sufficient vitamin D levels at the end of the winter. RESULTS: The results indicated that 89.7% of all the participants had a decrease in vitamin D levels from summer to winter: 14.7% of them were vitamin D-deficient, 36.8% had insufficient vitamin D concentrations and only 48.5% where able to maintain sufficient vitamin D. The optimal cutoff point to provide assurance of sufficient serum vitamin D at the end of the winter was 40 ng/mL at the end of the summer. Sex, age and vitamin D levels at the end of the summer were significant predictors of non-sufficient vitamin D at the end of the winter. CONCLUSIONS: In this age group, a dramatic reduction in vitamin D was observed over the follow-up period. Sufficient vitamin D at the end of the summer did not guarantee vitamin D sufficiency at the end of the winter. We found 40 ng/mL as an optimal cutoff point.

The antiepileptogenic effect of low-frequency stimulation on perforant path kindling involves changes in regulators of G-protein signaling in rat.

G-protein coupled receptors may have a role in mediating the antiepileptogenic effect of low-frequency stimulation (LFS) on kindling acquisition. This effect is accompanied by changes at the intracellular level of cAMP. In the present study, the effect of rolipram as a phosphodiesterase inhibitor on the antiepileptogenic effect of LFS was investigated. Meanwhile, the expression of αs- and αi-subunit of G proteins and regulators of G-protein signaling (RGS) proteins following LFS application was measured. Male Wistar rats were kindled by perforant path stimulation in a semi-rapid kindling manner (12 stimulations per day) during a period of 6days. Application of LFS (0.1ms pulse duration at 1Hz, 200 pulses, 50-150µA, 5min after termination of daily kindling stimulations) to the perforant path retarded the kindling development and prevented the kindling-induced potentiation and kindling-induced changes in paired pulse indices in the dentate gyrus. Intra-cerebroventricular microinjection of rolipram (0.25µM) partially prevented these LFS effects. Twenty-four hours after the last kindling stimulation, the dentate gyrus was removed and changes in protein expression were measured by Western blotting. There was no significant difference in the expression of α-subunit of Gs and Gi/o proteins in different experimental groups. However, application of LFS during the kindling procedure decreased the expression RGS4 and RGS10 proteins (that reduce the activity of Gi/o) and prevented the kindling-induced decrease of RGS2 protein (which reduces the Gs activity). Therefore, it can be postulated that the Gi/o protein signaling pathways may be involved in antiepileptogenetic effect of LFS, and this is why decreasing the cAMP metabolism by rolipram attenuates this effect of LFS.

Anticonvulsant effects of N6-cyclohexyladenosine microinjected into the CA1 region of the hippocampus on entorhinal cortex-kindled seizures in rats.

In this study, the role of adenosine A1 receptors of the hippocampal CA1 region in entorhinal cortex-kindled seizures was investigated in rats. Animals were kindled by daily electrical stimulation of the entorhinal cortex. In fully kindled rats, N(6)-cyclohexyladenosine (CHA; a selective A1 receptor agonist) and 1, 3-dimethyl-8-cyclopenthylxanthine (CPT; a selective A1 receptor antagonist) were microinfused bilaterally into the hippocampal CA1 region. Rats were stimulated and seizure parameters were measured. Results obtained showed that CHA (10 and 50 micro moles) decreased the afterdischarge duration (ADD) in the hippocampal CA1 region and entorhinal cortex, stage 5 seizure duration (S5D) and seizure duration (SD) only at the dose of 50 micro moles, and significantly increased the latency to stage 4 (S4L). Intrahippocampal CPT increased ADD and S5D, and significantly reduced the latency to stage 4 (S4L) at the dose of 10 micromoles. Pretreatment of rats with CPT (5 micro moles) before CHA (50 micro moles), significantly reduced the effect of CHA on seizure parameters. The results suggest that the CA1 region of the hippocampus plays an important role in spreading seizure spikes from the entorhinal cortex to other brain regions and activation of adenosine A1 receptors in this region participates in the anticonvulsant effects of adenosine agonists.

Tactile learning in rodents: Neurobiology and neuropharmacology.

Animal models of learning and memory have been the subject of considerable research. Rodents such as mice and rats are nocturnal animals with poor vision, and their survival depends on their sense of touch. Recent reports have shown that whisker somatosensation is the main channel through which rodents collect and process environmental information. This review describes tactile learning in rodents from a neurobiological and neuropharmacological perspective, and how this is involved in memory-related processes.

The role of adenosine A(1) receptors in the interaction between amygdala and entorhinal cortex of kindled rats.

In this study the effect of adenosine A(1) receptors of the entorhinal cortex (EC) and amygdala on kindled seizures was investigated. Animals were kindled by daily electrical stimulation of amygdala (group 1) or EC (group 2). In the fully kindled animals, N(6)-cyclohexyladenosine (CHA), a selective A(1) receptor agonist, and 1,3-dimethyl-8-cyclopenthylxanthine (CPT), a selective A(1) receptor antagonist, were microinjected bilaterally into the EC (group 1) or amygdala (group 2). The seizure parameters were measured at 5, 15, 60 and 120 min post injection. Obtained data showed that in group 1, intra-EC microinjection of CHA at concentration of 10 microM reduced amygdala- and, EC-afterdischarge duration and stage 5 seizure duration at 5, 15, 60 and 120 min post drug injection. It also increased the latency to stage 4 seizure but no alteration was observed in seizure stage. At concentrations of 0.1 and 1 microM, CHA reduced only EC-afterdischarge duration at 5 and 15 min post drug infusion. Bilateral microinjection CPT at concentrations of 5 and 10 microM into the EC did not alter seizure parameters. Intra-EC microinjection of CPT (5 microM), 5 min before CHA (10 microM), blocked the anticonvulsant effects of CHA. On the other hand, in group 2 animals, intra-amygdala CHA (10, 50 and 100 microM) or CPT (5 and 10 microM) had no significant effect on seizure parameters of EC-kindled rats. These results suggest that adenosine A(1) receptors activation of the EC may have an inhibitory effect on amygdala-kindled seizures. But, despite of reciprocal interconnections between these two regions, activation of the A(1) receptors of the amygdala has no effect on EC-kindled seizures.