Influence of Quercetin/Quercetin-Loaded Magnetic Nanoparticles on the Firing Patterns of Hippocampal Neurons in Control and Kainic Acid-Injected Rats
Journal Title: The 1st Annual Meeting of Georgian Center for Neuroscience Research - Year 2020, Vol 2, Issue 20
Abstract
Epilepsy is one of the most common brain disorders. Regular treatment with the antiepileptic drugs is useful for controlling disease. However, more than 35% of people experience a resistant form. Development of epilepsy is associated with imbalance between excitatory and inhibitory neurotransmitter systems. Excessive activation of excitatory amino-acid receptors determines the generation of reactive oxygen species (ROS) that can provoke seizure. Reduction of the total antioxidant status and increase of production of nitric oxide (NO) were also demonstrated. Therefore, restoring the excitation/inhibition balance, to scavenge ROS and to inhibit pathological NO might be a promising novel therapeutic antiepileptic strategy. Quercetin is one of the best candidates for this purpose: some of pharmacological effects of quercetin are well known, for example: anti-inflammatory, antibacterial, anti-cancer. In the central nervous system quercetin can regulate many ligand-gated ion channels, including GABA, glycinergic, kainate, 5-HT and nicotinic receptors. However, the use of quercetin has been limited due to its poor bioavailability. The modern approach to solve problem is usage of nanoparticles. The purpose of present research was to use an external static magnetic field exposure (ESMFE) for targeted delivery of quercetinloaded magnetic nanoparticles (Q-MNPs) and to investigate the effects of quercetin/Q-MNPS on electrophysiological parameters of baseline and evoked responses in the CA1 field of the hippocampus. In ketamine-anesthetized wild tape laboratory rats metal (constatntan) tripolar electrodes were stereotaxically implanted in to the both side of the hippocampus for the unipolar registration of the neuronal activity and bipolar stimulation of the CA1 field. Single and paired-pulse electrical stimulation protocol were administrated. After registering the baseline activity unilateral 5 tames KA injection were performed in the CA3 field of the hippocampus for the generation of epileptiform activity. To evaluate the effect of quercetin/Q-MNP on kainite-induced epileptiform activity tail vein injection of quercetin/QMNP were carried out under condition of 60 min ESMFE (1 Tesla). Recording of hippocampal neuronal activity and analyses of obtained data were performed using Chart5.5 software. For statistical analyses was used software PRIZM. Our experiment showed that quercetin as well as magnetic field itself did not significantly change the mean amplitude and the frequency of neuronal activity. Q-MNP decreased the amplitude and increased the frequency of background activity, Q-MNP induced depression of single evoked responses and changes in strength of PPfacilitation. Preliminary administration of Q-MNP but not quercetin statically reliably reduced the frequency and amplitudes of the repetitive epileptiform discharges caused by intrahippocampal injection of the KA. Our experiments suggests that Q-MNP has inhibitory effects on epileptiform discharges and the exposure of magnetic field improves target-delivery of the Q-MNP to the brain. (The work is supported by Shota Rustaveli National Science Foundation, grant FR17_629).
Authors and Affiliations
Nanuli Doreuli, Mariam Qurasbediani, Rusudan Ansiani, Mariam Chitasvili, Manana Chikovani, Besarion Partsvania
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