Anticonvulsant effect of neural regeneration peptide 2945 on pentylenetetrazol-induced seizures in rats

作者：Sajadian Azadeh; Esteghamat Sana; Karimzadeh Fariba; Eshaghabadi Arezou; Sieg Frank; Speckmann Erwin Josef; Meuth Sven; Seidenbecher Thomas; Budde Thomas; Gorj Ali^*

来源：Neuropeptides, 2015, 49: 15-23.

DOI：10.1016/j.npep.2014.11.002

• Neuroinflammation
• Epilepsy
• Neuropharmacology
• Brain
• In vivo

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 mu g/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 GABA(A) receptor alpha and beta subunits and GAD-65 in the hippocampus and somatosensory cortex of the rat brain. Intraperitoneal injection of NRP2945 at 20 mu g/kg prevented seizure attacks after PTZ injection. NRP2945 at doses of 5 and 10 mu g/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 GABA(A) receptor alpha and beta 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 GABA(A) and GAD-65 protein expression and/or protecting these components of GABAergic signalling from P12-induced alteration. Further studies are needed to elucidate the potential role of NRP2945 as an antiepileptic drug.

• 出版日期2015-2