Postnatal Repeated Mild Stress and DEγE Treatment Induce a Reduction of S of DBA/2J in Mice

S.      Loizzo; A.      Capasso; G.      Giuliani; A.      Loizzo

Abstract

The present paper evaluates the effect of DEγE on the epileptiform EEG activity in a mouse model of epilepsy, i.e., the DBA/2J epileptiform pattern and the DBA/2J audiogenic seizures. Repeated neonatal mild stress, such as manipulation of pups and a brief isolation from the dam performed daily for a few weeks, induces brain, behavioural and hormonal alterations which may perdure up to adult and senescent ages. Since DEγE (a well known β-endorphin fragment) was able to modulate the epileptiform activity in animal models, we started an investigation to verify whether DEγE could modulate epileptiform EEG activity in DBA/2J mice. Litters of DBA/2J mice born in our laboratories were used. Pups of the litter W once per day were separated from mam for ten minutes, weighed and injected with distilled water sc or DEγE (50 and 100 mg/kg), from day 2 to day 21 (weaning). At the age of 60-90 days, mice under general (ketamine-xylazine) plus local (xylocaine) anaesthesia were implanted with 4 stainless electrodes in the anterior and posterior sensorimotor cortex bilaterally. At least 6 days later, they were placed in a sound-proof room, and EEG and motor activity were recorded for 60 min. Two parameters were evaluated: sleep-wakefulness cycle and epileptiform activity. The latter parameter consisted of four different data: spikes, polispikes, series of spike-and-waves, and series of polispike-and-waves. Our results show that a chronic mild stress in neonatal period, as daily injection of distilled water sc., in adult age induced a significant reduction of mean number of series of polispike-and-wave versus control; this effect in mice, chronically treated with DEγE at both doses 50 ng/μL and 100 ng/μL, was also observed. Chronic neonatal mild stress also induced alterations in response to visual evoked potentials. Flash evoked potentials of mice injected with distilled water appeared with a significant delay of latency at the frequency of 1 Hz and at the lower intensity of luminous stimulation versus control; we observed the same trend in chronically treated with DEγE 50 and 100 ng/μL/mice. The results of our experiments indicate that adult mice which had received DEγE showed a consistent reduction in mean number of series of polispike-and-wave versus controls. Other epileptiform parameters in stressed mice did not show consistent alteration, neither sleep-wakefulness cycle did. Also audiogenic seizures did not show consistent differences between groups. We conclude that some, but not all epileptiform parameters in a genetic model of epilepsy in mice are sensitive to DEγE.

Keywords: Mild stress, Epilepsy, DBA/2J mice, DEγE