title: Anticonvulsant effect of neural regeneration peptide 2945 on pentylenetetrazol-induced seizures in rats.
abstract: Neuron regeneration peptides (NRPs) are small synthetic peptides that stimulate neural proliferation, migration, and differentiation with no apparent toxicity and high target specificity in CNS. The aim of this study was to investigate the effect of NRP2945 on seizure activity induced by pentylenetetrazol (PTZ) in rats. Using behavioural assessment and electrocorticographical recordings, the effects of different doses of NRP2945 (5-20 µg/kg) were tested on seizure attacks induced by PTZ injection. In addition, the effect of NRP2945 was evaluated on the production of dark neurons and expression of GABAA receptor α and β subunits and GAD-65 in the hippocampus and somatosensory cortex of the rat brain. Intraperitoneal injection of NRP2945 at 20 µg/kg prevented seizure attacks after PTZ injection. NRP2945 at doses of 5 and 10 µg/kg significantly decreased the total duration of seizure attacks and reduced the amplitude, duration and latency of epileptiform burst discharges induced by PTZ. In addition, the peptide significantly inhibited the production of dark neurons in the hippocampus and somatosensory cortex of epileptic rats. NRP2945 also significantly increased the expression of GABAA receptor α and β subunits and GAD-65 in the hippocampus and somatosensory cortex compared with PTZ treated rats. This study indicates that NRP2945 is able to prevent the seizure attacks and neuronal injuries induced by PTZ, likely by stimulating GABAA and GAD-65 protein expression and/or protecting these components of GABAergic signalling from PTZ-induced alteration. Further studies are needed to elucidate the potential role of NRP2945 as an antiepileptic drug.
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Sajadian
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran.
authors.forename: Sana
authors.initials: S
authors.lastname: Esteghamat
authors.affiliation: Departments of Neuroscience, School of Advanced Technology of Medical, Tehran Medical University, Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Karimzadeh
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran.
authors.forename: Arezou
authors.initials: A
authors.lastname: Eshaghabadi
authors.affiliation: CuroNZ Ltd, 29 Nugent Street, Grafton, Auckland, New Zealand.
authors.forename: Frank
authors.initials: F
authors.lastname: Sieg
authors.affiliation: Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
authors.forename: Erwin-Josef
authors.initials: EJ
authors.lastname: Speckmann
authors.affiliation: Department of Neurology, Westfälische Wilhelms-Universität Münster, Münster, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Meuth
authors.affiliation: Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Seidenbecher
authors.affiliation: Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Budde
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran; Department of Neurology, Westfälische Wilhelms-Universität Münster, Münster, Germany; Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Münster, Germany; Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster, Germany; Klinik und Poliklinik für Neurochirurgie, Westfälische Wilhelms-Universität Münster, Münster, Germany. Electronic address: gorjial@uni-muenster.de.
authors.forename: Ali
authors.initials: A
authors.lastname: Gorji
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage*; D010433:Pentylenetetrazole; D021122:Protein Subunits; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; C000603034:NRP2945; D009842:Oligopeptides; D021122:Protein Subunits; D011963:Receptors, GABA-A; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D010433:Pentylenetetrazole
keywords: Brain; Epilepsy; In vivo; Neuroinflammation; Neuropharmacology