Investigation of the effect of REM sleep deprivation on epileptic seizures caused by pentylenetetrazole in mice

Aim: To investigate whether different periods of rapid eye movement sleep deprivation (REM SD) contribute to seizure susceptibility, hippocampal oxidative status and balance of inhibition-excitation in the acute epilepsy model. Methods: REM SD was performed using the modified multiple platforms method on adult male BALB/c mice. Pentylentetrazol (PTZ) was injected to induce seizures and hippocampal total antioxidant status (TAS), total oxidant status (TOS), gamma aminobutyric acid (GABA), and glutamate levels were measured using the ELISA method. Results: PTZ-induced seizures following 8 h and 72 h REM SD significantly reduced the hippocampal TAS levels, but did not affect the TOS levels. In REM SD groups, especially after 8 hours of REM sleep loss, there was a significant increase in glutamate in PTZ induction. The hippocampal GABA levels were increased by PTZ-induced seizures after 72 h REM SD. PTZ- induction after 8 hours of RAM SD leads to a significant increase in the seizure duration. Conclusion: It can be speculated that the REM SD can contribute to seizure susceptibility by changing the oxidant-antioxidant balance and excitatory and inhibitory tone in the hippocampus

Effects of the phosphodiesterase type-5 inhibitor tadalafil on nociception, morphine analgesia and tolerance in rats

Aim: Tadalafil is a potent, selective and reversible inhibitor of phosphodiesterase type 5 (PDE5) enzyme breakdowning cyclic guanosine monophosphate (cGMP). In this study, we aimed to investigate the effects of tadalafil on nociception, morphine analgesia and tolerance. Methods: In this study, 54 Wistar Albino (230-250 g) male rats were used. First of all, four different doses (2, 4, 8, 16 mg/kg) were used to determine the optimum effective dose of tadalafil on nociception. Optimum activity was found at 8 mg/kg and animals were divided into six groups: Saline (S), 8mg/kg tadalafil, 5mg/kg morphine (M), M+ tadalafil, morphine tolerance (MT) and MT+ tadalafil. Saline was given to the control group, tadalafil intraperitoneally and morphine subcutaneously administered at the indicated doses. To develop tolerance to morphine, 10mg/kg morphine was injected daily in the morning and evening for five days and tolerance was evaluated with single dose of morphine on sixth days. The resulting analgesic effect was measured with hot plate and tail flick analgesia tests and recorded at 30th, 60th, 90th and 120th minutes. Results: Tadalafil showed anti-nociceptive effect when given alone at different doses (p<0.05). However, tadalafil significantly decreased the analgesic effect of morphine (p<0.05). In addition, tadalafil significantly increased the tolerance to morphine (p<0.05). Conclusions: The phosphodiesterase type 5 inhibitor tadalafil have anti-nociceptive properties and it decreases analgesic effect of morphine, in addition improves tolerance development. These effects probably may occur via NO/cGMP pathway. &nbsp

Positive effects of angiotensin-converting enzyme (ACE) inhibitor, captopril, on pentylenetetrazole-induced epileptic seizures in mice

Purpose: To evaluate the effects of an angiotensin-converting enzyme (ACE) inhibitor, captopril, on pentylenetetrazole (PTZ)-induced seizures and post-seizure hippocampal injury. Materials: Thirty-five male Balb-c mice weighing 30 - 33 g were divided into control, saline PTZ, s(erum physiologic 1 ml/kg as solvent), positive control (valproic acid 200 mg/kg), captopril (25 mg/kg/day for 7 days), and captopril (50 mg/kg/day for 7 days) groups. PTZ (60 mg/kg) was administered thirty minutes after medication administration to induce epileptic seizures. The animals were observed for 30 min to record Racine stages, the time of the first myoclonic jerk (FMJ), and the occurrence of the first generalized tonic-clonic seizure (GTCS). Cornu Ammonis (CA)1, CA2, CA3, and the dentate gyrus (DG) of the hippocampus underwent histopathological examinations. The levels of total oxidant status (TOS), oxidative stress markers (total antioxidant status, TAS), and oxidative stress index (OSI) were measured in the brain tissue. Results: Compared to PTZ group, 25 mg/kg captopril decreased seizure scores and delayed FMJ and GTCS (p < 0.05). Histopathological assessment demonstrated that both 25 and 50 mg/kg captopril alleviated neuronal injury in CA1, CA2, CA3, and DG compared to PTZ (p < 0.05). Also, TOS and OSI levels in the brain tissue were reduced by both 25 and 50 mg/kg doses of captopril (p < 0.05). Conclusion: Captopril favorably improves epileptic seizure parameters and acts against post-seizure neuronal injury in the hippocampus. Captopril may be a drug of choice in epileptic individuals with hypertension. Keywords: Captopril, Angiotensin-converting enzyme, Epilepsy, Pentylenetetrazole, Neuronal damag

Ghrelin receptor agonist hexarelin attenuates antinociceptive tolerance to morphine in rats

Ghrelin is a peptide hormone released from the gastric endocrine glands and shows analgesic activity apart from its various physiological effects. Nevertheless, the effects of ghrelin receptor (GHS-R) agonists on morphine analgesia and tolerance have not been elucidated yet. The purpose of the study was to evaluate the effects of the ghrelin receptor agonist hexarelin and antagonist [D-Lys3]-GHRP-6 on morphine antinociception and tolerance in rats. A total of 104 Wistar albino male adults rats (weighing approximately 220-240 g) were used in the experiments. To induce morphine tolerance a 3-day cumulative dose regimen was used in rats. Then, randomly selected rats were evaluated for morphine tolerance on day 4. The analgesic effects of hexarelin (0.2 mg/kg), [D-Lys3]-GHRP-6 (10 mg/kg), and morphine (5 mg/kg) were measured at 30-min intervals (0, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. The findings suggest that hexarelin in combination with morphine attenuates analgesic tolerance to morphine. On the other hand, ghrelin receptor antagonist [D-Lys3]-GHRP-6 has no significant analgesic activity on the morphine tolerance in analgesia tests. Besides, co-administration of hexarelin and morphine increases the analgesic effect. In conclusion, these data indicate that administration of GHS-R agonist hexarelin with morphine enhances the antinociception and attenuates morphine tolerance.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Effect of ovarian stimulation on the expression of piRNA pathway proteins.

PIWI-interacting RNAs (piRNAs) play an important role in gametogenesis, fertility and embryonic development. The current study investigated the effect of different doses of pregnant mare serum gonadotrophin/human chorionic gonadotrophin (PMSG/hCG) and repeated ovarian stimulation (OS) on the expression of the Mili, Miwi, Mael, Tdrd1, Tdrd9, qnd Mitopld genes, which have crucial roles in the biogenesis and function of piRNAs. Here, we found that after treatment with 7.5 I.U. PMSG/hCG and two repeated rounds of OS, both the mRNA and protein levels of Tdrd9, Tdrd1 and Mael showed the greatest decrease in the ovarian tissue, but the plasma E2 levels showed the strongest increases (p<0.05). However, we found that the Mitopld, Miwi and Mili gene levels were decreased significantly after treatment with 12.5 I.U. PMSG/hCG. Our results suggested that exogenous gonadotropin administration leads to a significant decrease in the expression of the Mili, Miwi, Mael, Tdrd1, Tdrd9 and Mitopld genes, which are critically important in the piRNA pathway, and the changes in the expression levels of Tdrd9, Tdrd1 and Mael may be associated with plasma E2 levels. New comprehensive studies are needed to reduce the potential effects of OS on the piRNA pathway, which silences transposable elements and maintains genome integrity, and to contribute to the safety of OS

Comparison of Analgesic Effects Induced by Different Strengths of Extremely Low-Frequency Electromagnetic Fields

WOS: 000439206700006Objective: Our aim was to compare the results of the most commonly used analgesic measurement techniques and to determine the time and intensity at which the analgesic effects of the magnetic field (MF) are most effective. Methods: This study compared the analgesic effect of MF strengths (1, 5, and 10 mT) in 30 adults, male Wistar albino rats weighing 200-250 g. The analgesic effects were measured using tail-flick (TF) and hot-plate (HP) tests. To determine the optimum MF strength, rats were assigned into four groups: sham group and exposed to 1, 5, and 10 mT MF groups. Rats were placed in a solenoid, and MF of 50 Hz for 165 min was administered daily for 15 days. All four groups were kept in the solenoid for 165 min/15 days and exposed to MF. However, the analgesic effect was measured only on day 0, 4, 7, 11, and 15 using TF and HP tests. The latencies of analgesia were converted to a percentage of maximal antinociceptive effects (% MPE). Results: When the maximum analgesic effect of the 5 mT MF was determined on the seventh day, the% MPEs were 5.37 +/- 0.51, 13.66 +/- 1.27, 25.89 +/- 3.00, and 25.37 +/- 2.41 in the sham, 1 mT, 5 mT, and 10 mT groups, respectively. The optimum effect was observed with 5 mT MF on the seventh day and with 90 min in the solenoid. Conclusion: We didn't find any differences between the analgesic responses to the TF and HP tests.Cumhuriyet University Scientific Research Project (CUBAP, Turkey)Cumhuriyet University [T-652]This study was funded by Cumhuriyet University Scientific Research Project (T-652, CUBAP, Turkey)

Effects of post-learning REM sleep deprivation on hippocampal plasticity-related genes and microRNA in mice

Sleep is essential for memory consolidation that stabilizes a memory trace. Memory consolidation includes waves of new gene expression and protein synthesis. Recently, microRNAs (miRNAs) have emerged as critical regulators of memory processes. Previous studies demonstrated that rapid eye movement (REM) sleep deprivation (REM SD) during specific time windows after training in the Morris water maze (MWM) task impairs memory consolidation. Here, we showed that the post-learning REM sleep, extending from 3 to 6 h after last training, is critical for spatial learning in the MWM task. Further, we found that the REM SD after training significantly changes the hippocampal expression of brain-derived neurotrophic factor (BDNF) mRNA; however, it causes minimal difference in the hippocampal expressions of calcium-calmodulin-dependent protein kinase II (CAMKII) and cAMP response-element-binding (CREB). In addition, it considerably affected the hippocampal expressions of miR-132, miR-182, and miR-124. In conclusion, after the MWM task, the post-learning REM sleep during specific time windows can modulate spatial memory consolidation, and its deprivation can impact the hippocampal transcriptional processes including memory-related miRNAs and mRNAs