Effects of neuropeptide S on seizures and oxidative damage induced by pentylenetetrazole in mice

Abstract

Neuropeptide S (NPS) and its receptor were recently discovered in the central nervous system. In rodents, NPS promotes hyperlocomotion, wakefulness, anxiolysis, anorexia, and analgesia and enhances memory when injected intracerebroventricularly (i.c.v.). Herein, NPS at different doses (0.01, 0.1 and 1nmol) was i.c.v. administered in mice challenged with pentylenetetrazole (PTZ; 60mg/kg) repeatedly injected. Aiming to assess behavioral alterations and oxidative damage to macromolecules in the brain, NPS was injected 5min prior to the last dose of PTZ. The administration of NPS only at 1nmol increased the duration of seizures evoked by PTZ, without modifying frequency and latency of seizures. Biochemical analysis revealed that NPS attenuated PTZ-induced oxidative damage to proteins and lipids in the hippocampus and cerebral cortex. In contrast, the administration of NPS to PTZ-treated mice increased DNA damage in the hippocampus, but not cerebral cortex. In conclusion, this is the first evidence of the potential proconvulsive effects of NPS in mice. The protective effects of NPS against lipid and protein oxidative damage in the mouse hippocampus and cerebral cortex evoked by PTZ-induced seizures are quite unexpected. The present findings were discussed analyzing the paradoxical effects of NPS: facilitation of convulsive behavior and protection against oxidative damage to lipids and proteins.

Neuropeptide S Receptor as an Innovative Therapeutic Target for Parkinson Disease

“…Castro et al [ 18 , 21 ] showed reduced carbonylated proteins and lipid peroxidation in a mouse brain after NPS central administration. The protective effects of NPS against oxidative damage to macromolecules were observed when mice received pentylenetetrazole, a GABA A antagonist used for inducing seizures and damage to macromolecules [ 74 ]. In parkinsonian rats, 7 days of central treatment with NPS (1 nmol, once a day for 7 consecutive days), given after 6-OHDA administration, prevented the degeneration of TH-positive nigral neurons [ 11 , 13 , 14 ].…”

Effect of captopril on oxidative damage in pentylenetetrazole induced SHSY-5Y human neuroblastoma cell line

“…Epileptic seizures lead to neuronal death via aggravating calcium influx into cells. Thus, the brain neuro-degenerates, particularly in the hippocampus, and changes the function of variable synapses that store information, which may be a statement of the observed learning disorder following seizure 5,6 . Experimental epilepsy models have been performed to explain the basic mechanisms include in epileptic seizures.…”