title: Endocannabinoid-dependent protection against kainic acid-induced long-term alteration of brain oscillations in guinea pigs.
abstract: Changes in rhythmic activity can serve as early biomarkers of pathological alterations, but it remains unclear how different types of rhythmic activity are altered during neurodegenerative processes. Glutamatergic neurotoxicity, evoked by kainic acid (KA), causes hyperexcitation and acute seizures that result in delayed brain damage. We employed wide frequency range (0.1-300Hz) local field potential recordings in guinea pigs to study the oscillatory activity of the hippocampus, entorhinal cortex, medial septum, and amygdala in healthy animals for three months after KA introduction. To clarify whether the activation of endocannabinoid (eCB) system can influence toxic KA action, AM404, an eCB reuptake inhibitor, and URB597, an inhibitor of fatty acid amide hydrolase, were applied. The cannabinoid CB1 receptor antagonist AM251 was also tested. Coadministration of AM404 or URB597 with KA reduced acute behavioral seizures, but electrographic seizures were still registered. During the three months following KA injection, various trends in the oscillatory activities were observed, including an increase in activity power at all frequency bands in the hippocampus and a progressive long-term decrease in the medial septum. In the KA- and KA/AM251-treated animals, disturbances of the oscillatory activities were accompanied by cell loss in the dorsal hippocampus and mossy fiber sprouting in the dentate gyrus. Injections of AM404 or URB597 softened alterations in electrical activity of the brain and prevented hippocampal neuron loss and synaptic reorganization. Our results demonstrate the protective potential of the eCB system during excitotoxic influences.
authors.affiliation: Laboratory of Systemic Organization of Neurons, Institute of Theoretical and Experimental Biophysics of Russian Academy of Sciences, 3 Institutskaya Str., Pushchino, Moscow Region 142290, Russian Federation. Electronic address: shubina.lu@iteb.ru.
authors.forename: Liubov
authors.initials: L
authors.lastname: Shubina
authors.affiliation: Laboratory of Biophysics of Active Media, Institute of Theoretical and Experimental Biophysics of Russian Academy of Sciences, 3 Institutskaya Str., Pushchino, Moscow Region 142290, Russian Federation; Computer Science Department, Moscow Institute of Physics and Technology, 9 Institutskiy Per., Dolgoprudny, Moscow Region 141700, Russian Federation.
authors.forename: Rubin
authors.initials: R
authors.lastname: Aliev
authors.affiliation: Laboratory of Systemic Organization of Neurons, Institute of Theoretical and Experimental Biophysics of Russian Academy of Sciences, 3 Institutskaya Str., Pushchino, Moscow Region 142290, Russian Federation; Department of Biophysics and Biomedicine, Pushchino State Institute of Natural Sciences, 3 Nauki Pr., Pushchino, Moscow Region 142290, Russian Federation.
authors.forename: Valentina
authors.initials: V
authors.lastname: Kitchigina
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism; D063388:Endocannabinoids / Q000494:pharmacology* / Q000627:therapeutic use*; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects; D007608:Kainic Acid / Q000009:adverse effects / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced; D013226:Status Epilepticus / Q000139:chemically induced
chemical_list: D063388:Endocannabinoids; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; D007608:Kainic Acid
keywords: AM404; Amygdala; Entorhinal cortex; Hippocampus; Medial septum; URB597