Suppressive effects of resveratrol treatment on the intrinsic evoked excitability of CA1 pyramidal neurons

Objective: Resveratrol, a phytoalexin, has a wide range of desirable biological actions. Despite a growing body of evidence indicating that resveratrol induces changes in neuronal function, little effort, if any, has been made to investigate the cellular effect of resveratrol treatment on intrinsic neuronal properties. Materials and Methods: This experimental study was performed to examine the acute effects of resveratrol (100 μ M) on the intrinsic evoked responses of rat Cornu Ammonis (CA1) pyramidal neurons in brain slices, using whole cell patch clamp recording under current clamp conditions. Results: Findings showed that resveratrol treatment caused dramatic changes in evoked responses of pyramidal neurons. Its treatment induced a significant (P<0.05) increase in the after hyperpolarization amplitude of the first evoked action potential. Resveratrol-treated cells displayed a significantly broader action potential (AP) when compared with either control or vehicle-treated groups. In addition, the mean instantaneous firing frequency between the first two action potentials was significantly lower in resveratrol-treated neurons. It also caused a significant reduction in the time to maximum decay of AP. The rheobase current and the utilization time were both significantly greater following resveratrol treatment. Neurons exhibited a significantly depolarized voltage threshold when exposed to resveratrol. Conclusion: Results provide direct electrophysiological evidence for the inhibitory effects of resveratrol on pyramidal neurons, at least in part, by reducing the evoked neural activity

A dose-effect study of cisplatin ototoxicity in Albino Guinea pigs

Introduction: Cisplatin is one of the most commonly used antineoplastic drugs; nonetheless, its ototoxic dose-limiting side effects have remained a significant challenge in clinical practice. The recognition of the exact template of hearing loss induced by multiple low doses of cisplatin could be of great help in managing the treatment process. The present study aimed to investigate the effects of multiple doses of this drug on the auditory system. Material and Methods: The present study was performed using an experimental guinea pig model in four groups as follows: 1-0.9 sodium chloride solution, 2-total dose of 7.5 mg/kg Cisplatin, 3-total dose of 10 mg/kg Cisplatin, and 4-total dose of 12.5 mg/kg cisplatin. The drugs were injected as 2.5 mg/kg/daily IP access in all groups. The auditory brainstem response (ABR) test was performed before the treatment and after every injection on a daily basis up to 72 h after the last injection. Results: There was dose-dependent significant hearing loss in all evaluated frequencies in three cisplatin groups. The general template of induced hearing loss during experimental days was almost the same in groups Cis7.5 and Cis10. In Cis 12.5 group, there was a jump in the threshold shift on the 5th day of the experiment and an upward trend in the function. Conclusion: As evidenced by the obtained results, the monitoring of hearing loss after every injection in patients who receive the drug and detecting the exact dose-dependent pattern of the induced hearing loss is of great help in controlling its undesirable destructive side effects on the auditory system. © 2020 Mashhad University of Medical Sciences. All rights reserved

Ionic currents in Helix aspersa neurones

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The effect of mebudipine and dibudipine, two new Ca2+ channel blockers, in comparison with nifedipine on Ca2+ spikes of F1 neuronal soma membrane in Helix aspersa

Mebudipine and dibudipine are two new dihydropyridine (DHP) Ca2+ channel blockers that have been synthesized by Mahmoudian et al. (1997). In previous studies, they showed considerable relaxant effect on vascular and ileal smooth muscles. These two compounds also reduced the contraction force of rat left atrium (20, 22). In the present study, we attempted to compare the inhibitory actions of these new DHPs and nifedipine on the high threshold Ca2+ spikes of F1 neuronal soma membrane in the subesophageal ganglia of Helix aspersa, using current-clamp method. At a concentration of 1 μM, two new DHP compounds (mebudipine and dibudipine) were tested for their L-type Ca2+ channel blocker activity. Both ocmpounds reversibily reduced the peak amplitude of action potential and after hyperpolarization potential and markedly decreased the duration of Ca2+ spikes. The most potent of these DHPs was mebudipine. Neither the two new DHPs nor nifedipine changed the resting membrane potential in a statistically significant way

Profound Alterations in the Intrinsic Excitability of Cerebellar Purkinje Neurons Following Neurotoxin 3-Acetylpyridine (3-AP)-Induced Ataxia in Rat: New Insights Into the Role of Small Conductance K+ Channels

Alterations in the intrinsic properties of Purkinje cells (PCs) may contribute to the abnormal motor performance observed in ataxic rats. To investigate whether such changes in the intrinsic neuronal excitability could be attributed to the role of Ca2+-activated K+ channels (K-Ca), whole cell current clamp recordings were made from PCs in cerebellar slices of control and ataxic rats. 3-AP induced profound alterations in the intrinsic properties of PCs, as evidenced by a significant increase in both the membrane input resistance and the initial discharge frequency, along with the disruption of the firing regularity. In control PCs, the blockade of small conductance K-Ca channels by UCL1684 resulted in a significant increase in the membrane input resistance, action potential (AP) half-width, time to peak of the AP and initial discharge frequency. SK channel blockade also significantly decreased the neuronal discharge regularity, the peak amplitude of the AP, the amplitude of the after-hyperpolarization and the spike frequency adaptation ratio. In contrast, in ataxic rats, both the firing regularity and the initial firing frequency were significantly increased by the blockade of SK channels. In conclusion, ataxia may arise from alterations in the functional contribution of SK channels, to the intrinsic properties of PCs

Enhancement of Purkinje Neuronal Excitability by the Inhibition of Fast Voltage Gated K+ Channel Function in Ataxic Rats

Objective: The purpose of this study was to investigate the role of fast inactivating (IA) voltage dependent potassium channels in shaping the discharge activity of cerebellarPurkinje cells (PCs) in ataxic rats.Materials and Methods: Male Sprauge-Dawley rats (40-60 g) were used in this study. Ataxia was induced via single i.p. injection of 3-acethylpyridine (65 mg/kg). Four days following induction of ataxia, the rats were decapitated after being anesthetizedusing ether. 300 μm thick parasagittal slices were prepared from the vermis of the cerebellum. Sharp intracellular recording was achieved from Purkinje cells under continuous superfusion of ACSF containing synaptic blockers.Results: Intracellular recording of 21 Purkinje neurons in cerebellar slice preparationshowed that Purkinje cells of ataxic rats fire in three modes of tonic (23.81%), burst (19.05%) and silence (57.14%). Following the application of 4-AP, 83.33% of the silent PCs were spontaneously fired and the burst activity was robustly enhancedin bursting PCs. In addition, 4-AP significantly increased the duration of burst and active periods but decreased the duration of inactive period. It also increased the number of sodium spikes within each burst.Conclusion: 4-AP sensitive current in Purkinje cell of ataxic rat involves in three modes of firing pattern. In addition, the inhibition of fast inactivating potassium channels(IA) with 4-AP enhances the spontaneous discharge activity of Purkinje cells

The Measurement of Low Frequency Magnetic Field of Two Kinds of GSM900 Mobile Phone

Introduction:  The  use  of  mobile  communication  systems  has  dramatically  increased  over  the  past  decade. Although many studies have been performed to determine the effect of radio frequency (RF) but  less attention has been paid to the possible biological impact of exposure to extremely low frequency  (ELF) components.   The objective of this study is two folds. One is to design the equipments needed for the measurement of  the ELF fields of two types of GSM900 mobile phone. Secondly, use a protocol suitable for an accurate  assessment of the ELF fields.  Materials  and Methods:  First  a  home-made  search  coil  was  provided  and  calibrated precisely  under  several experiments. Using Fast Fourier Transform, the power spectrum density of the induced voltage in  the search coil was analyzed and the amplitudes of 217 Hz and its harmonics were extracted and then the  distribution of magnetic field in the back side of mobile phones was determined.  Results: The values of B-field on the back side of the two kinds of GSM mobile phone were different.  They  were  between  50  to  160  µT in  Nokia  3310  and  14  to  30  µT in  Nokia  8310.  Considering  the  difference between the amplitudes of frequency components at 217 Hz and its harmonics in the two kinds  of mobile phone, a range of magnetic flux density at different times in a five day period was measured.  Discussion and Conclusion: These findings emphasize the need for considering the distribution of low  frequency magnetic field from mobile phone when biological effects of magnetic fields are studied. To  determine  the  intensity  windowing  effect,  one  must  consider  the  physical  characteristics  of  the  fundamental  frequency  component  wave  (217  Hz)  and  its  harmonics  produced  by  the  mobile  phone  similar to the one generated under a real situation

The role of potassium channels in the regulation of calcium spike configuration in the cerebellar Purkinje neurons

Background: Calcium spikes play important roles in the control of neuronal spontaneous activity. Cerebellar Purkinje neurons fire spontaneous calcium spikes. In this study, the role of potassium channels in the regulation of these spikes was studied. Materials & Methods: Brain slices from the cerebellum of young rats were prepared and the Purkinje cells were visualized using an upright microscope. Using borosilicate micropipettes and Axoclamp 2B amplifier, intracellular recordings were taken from the cells. The role of different K+ channels in the regulation of calcium spikes configuration was determined using different K+ channels blockers and precise analysis of the recorded calcium spikes in the presence of blockers. Results: Application of wide-range 4-aminophyridine and tetraethylammonium blockers increased duration and amplitude of afterhyperpolarization (AHP) of the calcium spikes and converted them from one-peak spike to two- or multiple-peaks spikes. Blockade of small conductance calcium dependent potassium channels increased duration of the spikes but had no effect on the AHP amplitude Blockade of large conductance calcium dependent potassium channels increased duration of the calcium spikes and decreased the AHP amplitude. Conclusion: Our results showed that properties of the calcium spikes in the cerebellar Purkinje neurons were largely controlled by different potassium channels, including calcium dependent types

Alterations in ca1 pyramidal neuronal intrinsic excitability mediated by iH channel currents in a rat model of amyloid beta pathology

Amyloid beta (Aβ) accumulation plays an important role in the pathogenesis of Alzheimer's disease (AD) by changing the neuronal excitability. However, the cellular mechanisms by which accumulation of Ab affects intrinsic neuronal properties are not well understood. The effect of bilateral intra-frontal cortex Aβ (1-42) peptide injection on the intrinsic excitability of hippocampal CA1 pyramidal neurons with particular focus on the contribution of hyperpolarization-activated (Ih) channel currents was examined using whole-cell patch-clamp recording. Passive avoidance memory impairment and morphological changes in rats receiving intra-frontal Aβ treatment were observed, which was associated with significant changes both in passive and active intrinsic electrical membrane properties of CA1 pyramidal neurons. Electrophysiological recording showed a significant decrease in neuronal excitability associated with an augmentation in the first spike after-hyperpolarization (AHP) amplitude. In addition, the depolarizing sag voltage was altered in neurons recorded from Ab-treated group. In voltage-clamp condition, a hyperpolarizing activated inward current sensitive to ZD7288 and capsaicin was significantly increased in neurons from Aβ-treated rats. The Ih current density was increased and the activation curve was shifted toward less negative potential in the Aβ-treated group as compared to control group. The enhancing effect of Aβ treatment on Ih current was confirmed by showing upregulation of the mRNA of HCN1 channel in the CA1 pyramidal layer of hippocampi. These findings suggest the contribution of Ih and possibly TRPV1 channel currents to the changes induced by Aβ treatment in the intrinsic membrane properties, which, in turn, may provide therapeutic targets for treatment of AD. © 2015 IBRO

Ameliorating Effects of Dorema ammoniacum on PTZ-Induced Seizures and Epileptiform Brain Activity in Rats

The objective of the current study was to investigate the anti-epileptogenic and anticonvulsant effects of Dorema ammoniacum gum, which is used in Iranian traditional medicine for the treatment of seizures. Animals received pentylenetetrazol (IP, 30 mg/kg/48 h) for inducing seizures. Five different seizure stages were evaluated for 20 min and parameters including maximum seizure stage, the latency to the onset of stage 4, stage 4 duration, and seizure duration were measured. D. ammoniacum (50 and 100 mg/kg) or its vehicle was administered 30 min before or after pentylenetetrazol injection in different groups. In addition, the effective dose of D. ammoniacum (100 mg/kg) on different seizure stages was compared with the common antiseizure drug phenobarbital. In another set of experiments, we investigated the effective dose of D. ammoniacum on fully kindled animals in which an interictal electroencephalogram was recorded by superficial electrodes placed on the skull. The results showed that D. ammoniacum administration, before and after pentylenetetrazol injections, significantly decreased seizure stage, seizure duration, stage 4 duration, and 1/stage 4 latency. The anti-epileptogenic effect of D. ammoniacum was about 50 to 60 of phenobarbital. In addition, D. ammoniacum significantly decreased seizure stage, seizure duration, stage 4 duration, and 1/stage 4 latency when administered to fully kindled animals but had no effect on the power of EEG sub-bands. These results indicate that D. ammoniacum has anti-epileptogenic and anticonvulsant effects in a chemical kindling model of seizures. © 2020 Georg Thieme Verlag. All rights reserved